Predictors of index admission mortality and morbidity in contemporary esophageal atresia patients.

BACKGROUND/PURPOSE: The Spitz classification for esophageal atresia with/without tracheoesophageal fistula (EA/TEF) predicts mortality. This study evaluates the contemporary relevance of the Spitz classification and investigates predictors of morbidity. METHODS: EA/TEF patients born between 1995 and 2018 at two centers were retrospectively reviewed. Clinical variables including sex, prenatal diagnosis, birth weight, prematurity, major congenital heart disease (MCHD), and pre-operative mechanical ventilation (POMV) were collected. Index admission composite morbidity was considered positive if: length-of-stay >90th percentile (139 days), ventilation days >90th percentile (24 days), and/or gastrostomy was used for long-term feeding. Multivariable regression determined predictors of index admission mortality and composite morbidity. A composite morbidity predictive algorithm was created. ROC curves evaluated model discrimination. RESULTS: Of 253 patients, 13 (5.1%) experienced index admission mortality. Of the patients not suffering mortality, 74 (31.6%) experienced composite morbidity. Only MCHD predicted mortality (p = 0.001); birth weight did not (p = 0.173). There was no difference between the Spitz classification and MCHD alone in predicting mortality risk (p = 0.198); both demonstrated very good discrimination. Prenatal diagnosis, POMV, prematurity, and male sex predicted composite morbidity risk (p < 0.001; p = 0.008; p = 0.009; p = 0.05). An algorithm incorporating these predictors demonstrated good discrimination (AUC = 0.784; 95% CI: 0.724, 0.844). CONCLUSIONS: The Spitz classification maintains contemporary relevance for mortality risk, though birth weight can be de-emphasized. A new morbidity risk algorithm is proposed for early postnatal counseling. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level IV.

Surgery for supraventricular tachycardia and congenital heart defects: long-term efficacy of the combined approach in adult patients.

AIMS: Supraventricular arrhythmias are a major cause of morbidity and mortality in adult patients with congenital heart disease (CHD). Intraoperative ablation offers an alternative for patients who failed ablation procedures or are requiring concomitant surgical intervention. We present our long-term results with the surgical treatment of arrhythmias in adults with CHD (ACHD) undergoing elective cardiac surgery and the clinical predictors for arrhythmia recurrence. METHODS AND RESULTS: Between 2002 and 2013, 80 consecutive patients with CHD, mean age of 39 years, underwent intraoperative ablation with monopolar irrigated radiofrequency during cardiac surgery procedures. Significant clinical predictors of arrhythmia recurrence were determined by univariate analysis. We performed 47 right-sided Maze procedures, and 33 Cox-Maze III procedures. In 75 survivors, the ablation was effective immediately. Over an average follow-up period of 72 months (12-155 months), arrhythmias recurred in nine (20%) patients after right-sided Maze, and in six (19%) patients after Cox-Maze III. Eleven patients were controlled with medical therapy, three underwent catheter ablation of the arrhythmia, and one required a permanent pacemaker. Preoperative arrhythmia length ≥3 years (P ≤ 0.001), tetralogy of Fallot (P ≤ 0.006), and preoperative atrial fibrillation (P ≤ 0.016) were associated with recurrence arrhythmia. Conversely, NYHA class <3 (P ≤ 0.047) was associated with a lower risk of recurrence. CONCLUSION: Surgical treatment of unresponsive supraventricular arrhythmia during concomitant cardiac surgery in ACHD is a safe and effective procedure. Freedom from arrhythmias recurrence is 75% after 6 years of follow-up. Long-term recurrence of arrhythmia in these patients seems to be strongly correlated to preoperative arrhythmia duration.

The NF-kB regulates the SHP-1 expression in monocytes in congestive heart failure.

It has been shown that functional recovery of patients with acute congestive heart failure (ACHF) after treatment with conventional drugs (CD) is mediated by suppression of inflammation in peripheral blood mononuclear cells. Here, we analyzed gene expression profiles of monocytes from symptomatic ACHF patients (NYHA Class III-IV) before and after pharmacological treatment with CD. The treatment was associated with selective down-regulation of "TNFR signaling" and pro-inflammatory mediators CCL5, MIP-1α receptor, CD14, ITGAM, and significant up-regulation of "TNFR signaling" as evidenced by increase in anti-inflammatory factors including NF-kBIA, TNFAIP3 and SHP-1. In monocyte TNF-alpha-stimulated there is a down-regulation of the phosphatase SHP-1 which induces a significant activation of TAK-1/IKK/NF-kB signaling. These findings suggest that the therapeutic impact of CD treatment in symptomatic ACHF includes negative regulation of the NF-kB signaling in monocytes and the improvement of the SHP-1 activity.

Diabetic human adipose tissue-derived mesenchymal stem cells fail to differentiate in functional adipocytes.

Adipose tissue dysfunction represents a hallmark of diabetic patients and is a consequence of the altered homeostasis of this tissue. Mesenchymal stem cells (MSCs) and their differentiation into adipocytes contribute significantly in maintaining the mass and function of adult adipose tissue. The aim of this study was to evaluate the differentiation of MSCs from patients suffering type 2 diabetes (dASC) and how such process results in hyperplasia or rather a stop of adipocyte turnover resulting in hypertrophy of mature adipocytes. Our results showed that gene profile of all adipogenic markers is not expressed in diabetic cells after differentiation indicating that diabetic cells fail to differentiate into adipocytes. Interestingly, delta like 1, peroxisome proliferator-activated receptor alpha, and interleukin 1ß were upregulated whereas Sirtuin 1 and insulin receptor substrate 1 gene expression were found downregulated in dASC compared to cells obtained from healthy subjects. Taken together our data indicate that dASC lose their ability to differentiate into mature and functional adipocytes. In conclusion, our in vitro study is the first to suggest that diabetic patients might develop obesity through a hypertrophy of existing mature adipocytes due to failure turnover of adipose tissue. Impact statement In the present manuscript, we evaluated the differentiative potential of mesenchymal stem cells (MSCs) in adipocytes obtained from healthy and diabetic patients. This finding could be of great potential interest for the field of obesity in order to exploit such results to further understand the pathophysiological processes underlying metabolic syndrome. In particular, inflammation in diabetic patients causes a dysfunction in MSCs differentiation and a decrease in adipocytes turnover leading to insulin resistance.

Predictors of Ominous Outcome in Infants who Undergo Cardiac Surgery and Cardiopulmonary By-Pass: S100B Protein.

S100B protein has been recently proposed as a consolidated marker of brain damage and death in adult, children and newborn patients. The present study evaluates whether the longitudinal measurement of S100B at different perioperative time-points may be a useful tool to identify the occurrence of perioperative early death in congenital heart disease (CHD) newborns. We conducted a case-control study in 88 CHD infants, without pre-existing neurological disorders or other co-morbidities, of whom 22 were complicated by perioperative death in the first week from surgery. Control group was composed by 66 uncomplicated CHD infants matched for age at surgical procedure. Blood samples were drawn at five predetermined timepoints before during and after surgery. In all CHD children, S100B levels showed a pattern characterized by a significant increase in protein's concentration from hospital admission up to 24-h after procedure reaching their maximum peak (P<0.01) during cardiopulmonary by-pass and at the end of the surgical procedure. Moreover, S100B concentrations in CHD death group were significantly higher (P<0.01) than controls at all monitoring time-points. The ROC curve analysis showed that S100B measured before surgical procedure was the best predictor of perioperative death, among a series of clinical and laboratory parameters, reaching at a cut-off of 0.1 µg/L a sensitivity of 100% and a specificity of 63.7%. The present data suggest that in CHD infants biochemical monitoring in the perioperative period is becoming possible and S100B can be included among a series of parameters for adverse outcome prediction.

Echocardiographic assessment after surgical repair of tetralogy of fallot.

Surgical correction of tetralogy of Fallot is still one of the most frequently performed intervention in pediatric cardiac surgery, and in many cases, it is far from being a complete and definitive correction. It is rather an excellent palliation that solves the problem of cyanosis, but predisposes the patients to medical and surgical complications during follow-up. The decision-making process regarding the treatment of late sequel is among the most discussed topics in adult congenital cardiology. In post-operative Fallot patients, echocardiography is used as the first method of diagnostic imaging and currently allows both a qualitative observation of the anatomical alterations and a detailed quantification of right ventricular volumes and function, of the right ventricular outflow tract, and of the pulmonary valve and pulmonary arteries. The literature introduced many quantitative echocardiographic criteria useful for the understanding of the pathophysiological mechanisms involving the right ventricle and those have made much more objective any decision-making processes.

Biochemical Markers for Brain Injury Monitoring in Children with or without Congenital Heart Diseases.

Perinatal asphyxia (PA) still constitutes a common complication involving a large number of infants with or without congenital heart diseases (CHD). PA affects 0.2-0.6% of full-term neonates, 20% of which suffer mortal hypoxic-ischemic encephalopathy, and among survivors 25% exhibit permanent consequences at neuropsychological level. Each year, about one third of 1000 live births underwent to surgical intervention in early infancy and/or are at risk for ominous outcome. Advances in brain monitoring, in anesthetic and cardiothoracic surgical techniques, including selective or total body cooling, cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest, have essentially reduced mortality expanding the possibility to address functional neurologic and cardiac outcomes in long-term survivors. However, open-heart surgery constitutes a time-frame of planned ischemia-reperfusion injury, which is a price to pay in the treatment or palliation of CHD. Infants who underwent heart surgery and non-CHD infants complicated by PA share similarities in their neurodevelopmental profile and a common form of brain damage due to hypoxic-ischemic injury. The purpose of the present review was to evaluate different mechanisms implicated in brain injury following CPB and PA and how it is possible to monitor such injury by means of available biomarkers (S100B protein, Activin A, Adrenomedullin).

Congenital langerhans cell histiocytosis with placental involvement.

Congenital presentations of Langerhans cell histiocytosis (LCH) are exceedingly rare, and concurrent placental parenchymal involvement has not been definitively documented in the literature. We present 2 cases of congenital multisystem LCH with placental involvement resembling chronic villitis. Placental examination may provide the initial diagnostic evidence of LCH and may significantly influence patient management and outcome; however, the prognostic implications remain unclear. In a clinical context suspicious for congenital LCH, the observation of chronic villitis should prompt consideration of placental involvement by LCH.

Anomalous origin of the right coronary artery from the pulmonary artery associated with tetralogy of Fallot: description of the pre-surgical diagnosis and surgical repair.

Anomalous origin of the right coronary artery from the pulmonary artery is a rare congenital defect. We describe the case of an infant with anomalous origin of the right coronary artery from the pulmonary artery in association with tetralogy of Fallot. This patient had a pre-operative echocardiographic diagnosis, which was confirmed by angiography, and later underwent a successful surgical repair.