Autograft and pulmonary allograft performance in the second post-operative decade after the Ross procedure: insights from the Rotterdam Prospective Cohort Study

Aims The objective of the present study was to report our ongoing prospective cohort of autograft recipients with up to 21 years of follow-up. Methods and results All consecutive patients (n = 161), operated between 1988 and 2010, were analysed. Mixed-effects models were used to assess changes in echocardiographic measurements (n = 1023) over time in both the autograft and the pulmonary allograft. The mean patient age was 20.9 years (range 0.05-52.7)-66.5% were male. Early mortality was 2.5% (n = 4), and eight additional patients died during a mean follow-up of 11.6 ± 5.7 years (range 0-21.5). Patient survival was 90% [95% confidence interval (CI), 78-95] up to 18 years. During the follow-up, 57 patients required a re-intervention related to the Ross operation. Freedom from autograft reoperation and allograft re-intervention was 51% (95% CI 38-63) and 82% (95% CI 71-89) after 18 years, respectively. No major changes were observed over time in autograft gradient, and allograft gradient and regurgitation. An initial increase of sinotubular junction and aortic anulus diameter was observed in the first 5 years after surgery. The only factor associated with an increased autograft reoperation rate was pre-operative pure aortic regurgitation (AR) (hazard ratio 1.88; 95% CI 1.04-3.39; P= 0.037). Conclusion We observed good late survival in patients undergoing autograft procedure without reinforcement techniques. However, over half of the autografts failed prior to the end of the second decade. The reoperation rate and the results of echocardiographic measurements over time underline the importance of careful monitoring especially in the second decade after the initial autograft operation and in particular in patients with pre-operative AR.     

An introduction to mixed models and joint modeling: analysis of valve function over time

An important target of many clinical studies is to identify biomarkers, including risk scores, with strong prognostic capabilities. While biomarker evaluations are commonly utilized to predict the progress of the disease at single time points, appropriate statistical tools to assess the prognostic value of serial biomarker evaluation are rarely used. The goal of this paper is to demonstrate flexible and appropriate statistical methodology to assess the predictive capability of serial echocardiographic measurements of allograft aortic valve function. Moreover, the concept of joint modeling of longitudinal and survival data to optimally utilize the relationship between repeated valve function measurements and time-to-death or time-to-reoperation, is introduced and illustrated. Optimal and suboptimal methods are illustrated using a prospective cohort of patients who survived aortic valve or root replacement with an allograft valve and who were followed clinically and echocardiographically over time.     

Joint modeling of two longitudinal outcomes and competing risk data

Aortic gradient and aortic regurgitation are echocardiographic markers of aortic valve function. Both are biomarkers repeatedly measured in patients with valve abnormalities, and thus, it is expected that they are biologically interrelated. Loss of follow‐up could be caused by multiple reasons, including valve progression related, such as an intervention or even the death of the patient. In that case, it would be of interest and appropriate to analyze these outcomes jointly. Joint models have recently received much attention because they cover a wide range of clinical applications and have promising results. We propose a joint model consisting of two longitudinal outcomes, one continuous (aortic gradient) and one ordinal (aortic regurgitation), and two time‐to‐events (death and reoperation). Moreover, we allow for more flexibility for the average evolution and the subject‐specific profiles of the continuous repeated outcome by using B‐splines. A disadvantage, however, is that when adopting a non‐linear structure for the model, we may have difficulties when interpreting the results. To overcome this problem, we propose a graphical approach. In this paper, we apply the proposed joint models under the Bayesian framework, using a data set including serial echocardiographic measurements of aortic gradient and aortic regurgitation and measurements of the occurrence of death and reoperation in patients who received a human tissue valve in the aortic position. The interpretation of the results will be discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

A Bayesian joint model for zero‐inflated integers and left‐truncated event times with a time‐varying association: Applications to senior health care

Population aging in most industrialized societies has led to a dramatic increase in emergency medical demand among the elderly. In the context of private health care, an optimal allocation of the medical resources for seniors is commonly done by forecasting their life spans. Accounting for each subject's particularities is therefore indispensable, so the available data must be processed at an individual level. We use a large and unique dataset of insured parties aged 65 and older to appropriately relate the emergency care usage with mortality risk. Longitudinal and time‐to‐event processes are jointly modeled, and their underlying relationship can therefore be assessed. Such an application, however, requires some special features to also be considered. First, longitudinal demand for emergency services exhibits a nonnegative integer response with an excess of zeros due to the very nature of the data. These subject‐specific responses are handled by a zero‐inflated version of the hierarchical negative binomial model. Second, event times must account for the left truncation derived from the fact that policyholders must reach the age of 65 before they may begin to be observed. Consequently, a delayed entry bias arises for those individuals entering the study after this age threshold. Third, and as the main challenge of our analysis, the association parameter between both processes is expected to be age‐dependent, with an unspecified association structure. This is well‐approximated through a flexible functional specification provided by penalized B‐splines. The parameter estimation of the joint model is derived under a Bayesian scheme.     

Early microcirculatory impairment during therapeutic hypothermia is associated with poor outcome in post-cardiac arrest children: A prospective observational cohort study

Aims of the study

This study aimed to evaluate if the microcirculation is impaired during and after therapeutic hypothermia (TH) in children with return of spontaneous circulation after cardiac arrest (CA) and to assess if microcirculatory impairment predicts mortality. This has been reported for post-CA adults, but results might be different for children because etiology, pathophysiology, and mortality rate differ.

Methods

This prospective observational cohort study included consecutive, non-neonatal post-CA children receiving TH upon intensive care admission between June 2008 and June 2012. Also included were gender-matched and age-matched normothermic, control children without cardiorespiratory disease. The buccal microcirculation was non-invasively assessed with Sidestream Dark Field Imaging at the start of TH, halfway during TH, at the start of re-warming, and at normothermia. Macrocirculatory, respiratory, and biochemical parameters were also collected.

Results

Twenty post-CA children were included of whom 9 died. During hypothermia, the microcirculation was impaired in the post-CA patients and did not change over time. At normothermia, the core body temperature and the microcirculation had increased and no longer differed from the controls. Microcirculatory deterioration was associated with mortality in the post-CA patients. In particular, the microcirculation was more severely impaired at TH start in the non-survivors than in the survivors – positive predictive value: 73–83, negative predictive value: 75–100, sensitivity: 63–100%, and specificity: 70–90%.

Conclusions

The microcirculation is impaired in post-CA children during TH and more severe impairment at TH start was associated with mortality. After the stop of TH, the microcirculation improves rapidly irrespective of outcome.     

Influence of Young Age on Outcome After Esophagectomy for Cancer

Background

The incidence of esophageal cancer has risen among all age groups. Controversy exists about the clinical presentation and prognosis of young patients. The aim of this study was to compare the clinicopathologic characteristics and outcomes after surgery between patients with esophageal cancer who were <50?years of age and those ≥50?years of age.

Methods

Patients diagnosed with esophageal carcinoma who underwent esophagectomy between January 1990 and December 2010 in a single institution were selected from a prospective database. Patients aged <50?years at diagnosis (n?=?163) were compared with those ≥50?years (n?=?1151) with respect to clinicopathologic stage and oncologic outcome.

Results

Younger patients had less co-morbidity (p?<?0.001). There were no significantly differences in tumor localization, histology, differentiation, or TNM stage in the two groups. In both groups, 37?% of the patients underwent neoadjuvant chemo(radio)therapy. One or more nonsurgical complications developed in 53?% of the older group versus 42?% in the younger group (p?=?0.012). In-hospital mortality was 6.3?% for patients ≥50?years compared to 1.8?% for younger patients (p?=?0.021). The 5?year overall survival was significantly better for the younger patients than for those ≥50?years (41 vs. 31?%, p?<?0.001), but median disease-specific and disease-free survival did not differ between the groups (37 vs. 30?months, p?=?0.140 and 49 vs. 28?months, p?=?0.079, respectively). Multivariate analysis identified moderate, poorly, and undifferentiated tumors; tumor-positive resection margins (pR1–2); and TNM stage IIB–IV as independent predictors of disease-specific survival.

Conclusions

A considerable proportion (12?%) of patients diagnosed with resectable esophageal carcinoma were <50?years. Phenotypic tumor characteristics and disease-specific survival were comparable for the two age groups.     

Airway disease on chest computed tomography of preschool children with cystic fibrosis is associated with school‐age bronchiectasis

Airway wall thickening and mucus plugging are important characteristics of cystic fibrosis (CF) lung disease in the first 5 years of life.The aim of this study is to investigate the association of lung disease in preschool children (age, 2‐6) with bronchiectasis and other clinical outcome measures in the school age (age >7). Deidentified computed tomography‐scans were annotated using Perth‐Rotterdam annotated grid morphometric analysis for CF. Preschool %disease (a composite score of %airway wall thickening, %mucus plugging, and %bronchiectasis) and %MUPAT (a composite score of %airway wall thickening and %mucus plugging) were used as predictors for %bronchiectasis and several other school‐age clinical outcomes. For statistical analysis, we used regression analysis, linear mixed‐effects models and two‐way mixed models. Sixty‐one patients were included. %Disease increased significantly with age (P < .01). Preschool %disease and %MUPAT were significantly associated with school‐age %bronchiectasis (P < .01 and P < .01, respectively). No significant association was found between preschool %disease and %MUPAT and school‐age forced expiratory volume 1 (FEV1%) predicted and quality of life (P > .05). Cross‐sectional, %disease in school‐age was associated with a low FEV1% predicted and low quality of life (P = .01 and P = .007, respectively). %Disease can be considered an early marker of diffuse airways disease and is a risk factor for school‐age bronchiectasis.