Congenitally corrected transposition of the great arteries outcomes of different surgical techniques in a paediatric population: A single-centre report.

BACKGROUND: Congenitally corrected transposition of the great arteries is a complex pathology characterised by atrioventricular and ventriculo-arterial discordance. Optimal surgical approaches are still a matter of debate. OBJECTIVE: To evaluate the outcomes of different surgical treatments in a single centre. METHODS: Between 1998 and 2020, 89 patients were studied. The cohort was divided into three groups: physiologic, anatomic, and univentricular repair. RESULT: Physiologic correction (56.18%) was associated with significant tricuspid valve regurgitation progress (42%) and complete AV block (30%) compared to anatomic repair. Right ventricular systolic dysfunction was developed in 14%. Instead, anatomic correction (30.34%) (double switch 59% and Rastelli type 40.7%) presented moderate to severe aortic regurgitation (4%) and left ventricular systolic dysfunction (11%). Complete AV block was developed in 14.8%. Rate of reintervention was 34% for physiologic and 26% for anatomic. Univentricular palliation (13.8%) presented no complications or late mortality during the follow-up. The overall survival at 5 and 10 years, respectively, was 80% (95% CI 69, 87) and 75% (95% CI 62, 84). There was no statistically significant difference in mortality between the groups (p log-rank = 0.5752). CONCLUSION: Management of congenitally corrected transposition of the great arteries remains a challenge. In this cohort, outcomes after physiologic repair were satisfactory in spite of the progression of tricuspid regurgitation and the high incidence of AV block. Anatomic repair improved tricuspid regurgitation but increased the risk of aortic regurgitation and left ventricular systolic dysfunction. The Fontan group showed the lowest incidence of complications.

Pulmonary root translocation in corrected transposition of great arteries with ventricular septal defect and pulmonary stenosis with dextrocardia.

We present 13 years old with history of cyanosis and diagnosis of congenitally corrected transposition of great arteries with ventricle septal defect and pulmonary stenosis with dextrocardia. He underwent modified Senning procedure with pulmonary root translocation. Postoperative recovery was uneventful and was extubated on postoperative day 1. Patient remained in sinus rhythm. Postoperative echocardiography showed good biventricular function with no baffle obstruction and mild pulmonary regurgitation with no significant left and right outflow tract obstruction. Patient was discharged on postoperative day 6 and remained asymptomatic on follow up at 3 months.

Left Ventricular Re-training: Feasibility and Effectiveness-What Are the Limits?

The concept of 're-training' the morphologic left ventricle (mLV) is based on the crude principle of applying a fixed afterload by means of pulmonary artery banding. The complex physiological, molecular and structural responses to banding are poorly understood, and complicated by the fact that re-training is undertaken in a variety of different morphological settings and age-groups. This article reviews the evidence for re-training in different situations with particular focus on the age at banding and on the best ways to assess suitability for subsequent repair. Particular importance is placed on the role of re-training in congenitally corrected transposition as this is the commonest current indication - looking at better ways to train the mLV, the role of combined pressure and volume loading, and more sophisticated ways of assessing the adequacy of training. Current evidence suggests that age at banding has a fundamental impact on ability to re-train and long-term mLV function with the best results being achieved in infancy and concerns at any attempt beyond 2 years of age.

Anatomic Repair of Corrected Transposition of the Great Arteries: The Double Switch.

The long-term outcome of patients with corrected transposition of the great arteries and associated lesions after physiologic repair is uncertain. Anatomic correction, utilizing the morphologic left ventricle as a systemic pumping chamber and the mitral valve as the systemic atrioventricular valve, is considered the preferred method, especially for patients with either tricuspid valve regurgitation, with Ebstein's malformation of the tricuspid valve, or with right ventricular dysfunction. The double switch employs both an atrial switch and arterial switch to "correct" the atrioventricular and ventriculoarterial discordance. Associated lesions are also repaired. The best outcomes with double switch are achieved with patients in the first few years of life even if reconditioning of morphologic left ventricle is required. However, the long-term function of the conduction system, the aortic valve, and the ventricles is variable and requires close surveillance.

Corrected Transposition: Anatomic Repair Using the Hemi-Mustard Atrial Baffle and Bidirectional Superior Cavopulmonary Connection.

Anatomic repair for congenitally corrected transposition requires thoughtful surgical planning at both initial (neonatal or late) presentation, and during definitive repair. An algorithmic approach to the overall management of this lesion, with its many associated intracardiac anomalies, is presented. Modified atrial switch with bidirectional superior cavopulmonary connection is commonly utilized and demonstrates favorable results through a 20-year experience. Herein, technical considerations learned during the implementation of this strategy are described and emphasize the concept, in selected cases, of native pulmonary root preservation by translocation as an adjunct that is uniquely suited by adopting this approach.

Mathematical modeling of atopic dermatitis reveals "double-switch" mechanisms underlying 4 common disease phenotypes.

BACKGROUND: The skin barrier acts as the first line of defense against constant exposure to biological, microbial, physical, and chemical environmental stressors. Dynamic interplay between defects in the skin barrier, dysfunctional immune responses, and environmental stressors are major factors in the development of atopic dermatitis (AD). A systems biology modeling approach can yield significant insights into these complex and dynamic processes through integration of prior biological data. OBJECTIVE: We sought to develop a multiscale mathematical model of AD pathogenesis that describes the dynamic interplay between the skin barrier, environmental stress, and immune dysregulation and use it to achieve a coherent mechanistic understanding of the onset, progression, and prevention of AD. METHODS: We mathematically investigated synergistic effects of known genetic and environmental risk factors on the dynamic onset and progression of the AD phenotype, from a mostly asymptomatic mild phenotype to a severe treatment-resistant form. RESULTS: Our model analysis identified a "double switch," with 2 concatenated bistable switches, as a key network motif that dictates AD pathogenesis: the first switch is responsible for the reversible onset of inflammation, and the second switch is triggered by long-lasting or frequent activation of the first switch, causing irreversible onset of systemic TH2 sensitization and worsening of AD symptoms. CONCLUSIONS: Our mathematical analysis of the bistable switch predicts that genetic risk factors decrease the threshold of environmental stressors to trigger systemic TH2 sensitization. This analysis predicts and explains 4 common clinical AD phenotypes from a mild and reversible phenotype through to severe and recalcitrant disease and provides a mechanistic explanation for clinically demonstrated preventive effects of emollient treatments against development of AD.

Triple switch' aortic and pulmonary root inversion and modified Senning procedure for anatomically complex left transposition of the great arteries with inlet ventricular septal defect and pulmonary stenosis.

Left transposition of the great arteries with inlet ventricular septal defect and pulmonary stenosis is a relatively uncommon cardiac malformation. Two surgical treatments are available: double switch or physiological correction. The choice of surgical technique depends on the results of a discussion between the family and the surgeon. Choosing the appropriate technique is challenging because all options present various complications and benefits. We present a 'triple switch' aortic and pulmonary root inversion and modified Senning procedure for an anatomically complex left transposition of the great arteries with an inlet ventricular septal defect and pulmonary stenosis.

Contemporary outcomes of the double switch operation for congenitally corrected transposition of the great arteries.

OBJECTIVE: To determine the contemporary outcomes of the double switch operation (DSO) (ie, Mustard or Senning + arterial switch). METHODS: A single-institution, retrospective review of all patients with congenitally corrected transposition of the great arteries undergoing a DSO. RESULTS: Between 1999 and 2019, 103 patients underwent DSO with a Mustard (n = 93) or Senning (n = 10) procedure. Segmental anatomy was (S, L, L) in 93 patients and (I, D, D) in 6 patients. Eight patients had heterotaxy and 71 patients had a ventricular septal defect. Median age was 2.1 years (range, 1.8 months-40 years), including 34 patients younger than age 1 year (33%). Median weight was 10.9 kg (range, 3.4-64 kg). Sixty-one patients had prior pulmonary artery bands for a median of 1.1 years (range, 14 days-12.9 years; interquartile range, 0.7-3.1 years). Median intensive care unit and hospital lengths of stay were 5 and 10 days, respectively. Median follow-up was 3.4 years (interquartile range, 1-9.8 years) and 5.2 years (interquartile range, 2.3-10.7 years) in 79 patients with >1 year follow-up. At latest follow-up, aortic, mitral, tricuspid valve regurgitation, and left ventricle dysfunction was less than moderate in 96%, 98%, 96%, and 93%, respectively. Seventeen patients underwent reoperation: neoaortic valve intervention (n = 10), baffle revision (n = 5), and ventricular septal defect closure (n = 4). At latest follow-up, 17 patients (17%) had a pacemaker and 27 (26%) had cardiac resynchronization therapy devices. There were 2 deaths and 2 transplants. Transplant-free survival was 94.6% at 5 years. Risk factors for death or transplant included longer cardiopulmonary bypass time and older age at DSO. CONCLUSIONS: The outcomes of the DSO are promising. Earlier age at operation might favor better outcomes. Progressive neoaortic regurgitation and reinterventions on the neo-aortic valve are anticipated problems.

The Efficacy and Safety of Switching From Originator Infliximab to Single or Double Switch Biosimilar Among a Nationwide Cohort of Inflammatory Bowel Disease Patients.

Background: Data on safety and efficacy of switching to Renflexis (SB2) from originator Infliximab (IFX) (single switch) or from originator IFX to Inflectra (CT-P13) to Renflexis (double switch) are limited. Methods: We conducted a retrospective cohort study in a nationwide cohort of patient with inflammatory bowel disease (IBD) in remission who were switched to SB2. The main exposure was the treatment course of SB2. There are 2 levels in this variable: single switch (IFX to SB2) and double switch (IFX to CT-P13 to SB2). The outcome is SB2 drug discontinuation rate and/or not being in remission after 1 year. Logistic regression was used to estimate the adjusted and unadjusted odds ratios with 95% confidence intervals to study the efficacy difference between single switch and double switch. Results: A total of 271 IBD patients were started on SB2. Among them 52 (19.2%) patients did not achieve remission at 1 year and 14 (5.1%) patients had to discontinue SB2 due to adverse events). In logistic regression analysis after controlling for covariates, there was no statistically significant difference observed in regard to efficacy or safety of the single switch versus double switch to SB2 (adjusted odds ratio for double switch compared to single switch = 1.33 (95% confidence interval 0.74-2.41, P = 0.3432). Conclusions: Among IBD patients in remission, double switch was equally effective as compared to a single switch. This will help reassure the gastroenterologists who have concerns regarding the safety and efficacy of switching between multiple biosimilars for treating IBD.

Pulmonary root translocation and Senning procedure for congenitally corrected transposition of great arteries with pulmonary stenosis: a case report.

Congenitally corrected transposition of the great arteries (CCTGAs) is a condition, which includes atrioventricular and ventriculoarterial discordant connections along with ventricular septal defect (VSD), pulmonary stenosis (PS), or pulmonary atresia (PA). Without treatment, progressive systemic ventricular failure begins, which is followed by sudden cardiac death by the fourth or fifth decade. We report a case of a 4-year-old with CCTGA, VSD, and PS operated by Senning procedure and pulmonary root translocation (PRT) with uneventful postoperative recovery. PRT overcomes problems with the right ventricle to the pulmonary artery conduit and maintains pulmonary valve function and growth capacity. Our initial experience with PRT in CCTGA indicates that it is a feasible surgical alternative for such patients.

Systematic review and meta-analysis of outcomes of anatomic repair in congenitally corrected transposition of great arteries.

BACKGROUND: Treatment of congenitally corrected transposition of great arteries (cc-TGA) with anatomic repair strategy has been considered superior due to restoration of the morphologic left ventricle in the systemic circulation. However, data on long term outcomes are limited to single center reports and include small sample sizes. AIM: To perform a systematic review and meta-analysis for observational studies reporting outcomes on anatomic repair for cc-TGA. METHODS: MEDLINE and Scopus databases were queried using predefined criteria for reports published till December 31, 2017. Studies reporting anatomic repair of minimum 5 cc-TGA patients with at least a 2 year follow up were included. Meta-analysis was performed using Comprehensive meta-analysis v3.0 software. RESULTS: Eight hundred and ninety-five patients underwent anatomic repair with a pooled follow-up of 5457.2 patient-years (PY). Pooled estimate for operative mortality was 8.3% [95% confidence interval (CI): 6.0%-11.4%]. 0.2% (CI: 0.1%-0.4%) patients required mechanical circulatory support postoperatively and 1.7% (CI: 1.1%-2.4%) developed post-operative atrioventricular block requiring a pacemaker. Patients surviving initial surgery had a transplant free survival of 92.5% (CI: 89.5%-95.4%) per 100 PY and a low rate of need for pacemaker (0.3/100 PY; CI: 0.1-0.4). 84.7% patients (CI: 79.6%-89.9%) were found to be in New York Heart Association (NYHA) functional class I or II after 100 PY follow up. Total re-intervention rate was 5.3 per 100 PY (CI: 3.8-6.8). CONCLUSION: Operative mortality with anatomic repair strategy for cc-TGA is high. Despite that, transplant free survival after anatomic repair for cc-TGA patients is highly favorable. Majority of patients maintain NYHA I/II functional class. However, monitoring for burden of re-interventions specific for operation type is very essential.

Urgent double switch operation in a patient with congenitally corrected transposition of great arteries and an untrained systemic ventricle.

Congenitally corrected transposition of the great arteries is a rare cardiac abnormality. A nine-month-old male infant with the diagnosis of congenitally corrected transposition of the great arteries was admitted to our clinic with a history of pulmonary artery banding to train the left ventricle three months ago. On admission, he presented with bronchopneumonia, cyanosis, dyspnea, and severe biventricular heart failure associated with significant valvular regurgitation. An urgent double switch operation was performed with atrial and arterial switch procedures. Eight days of mechanical circulatory support was deemed mandatory following surgery. The patient is still under follow-up uneventfully three years after the operation.

A Double-Switch Temperature-Sensitive Controlled Release Antioxidant Film Embedded with Lyophilized Nanoliposomes Encapsulating Rosemary Essential Oils for Solid Food.

In order to match the solid food oxidation during logistics and storage process under severe high temperature, a double-switch temperature-sensitive controlled release antioxidant film embedded with lyophilized nanoliposomes encapsulating rosemary essential oils (REOs) was prepared. The double switch temperature at 35.26 and 56.98 °C was achieved by development of a temperature sensitive polyurethane (TSPU) film. With biaxially oriented polyethylene terephthalate (BOPET) as a barrier layer, the intelligent complex film was prepared via coating the TSPU embedded with lyophilized nanoliposomes encapsulating REOs on BOPET. The results indicate that the REO is well encapsulated in nanoliposomes with encapsulation efficiency (EE) of 67.3%, high stability and lasting antioxidant effect during 60 days. The incorporation of lyophilized nanoliposomes containing REOs into TSPU remains the double-switch temperature-sensitive characteristic of the prepared TSPU. In agreement with porosity and WVTR results, the diffusion coefficient (D) of the antioxidant complex film sharply increases respectively at two switching temperatures, indicating that the intelligent double-switch temperature-sensitive controlled release property is functioning. Furthermore, compared with films directly added with REO, the lower Ds of films added with lyophilized nanoliposomes encapsulating REOs provides a longer-lasting antioxidant activity. Thus, the acquired controlled release antioxidant film sensitive to temperature at 39.56 and 56.00 °C can be potentially applied for protection of solid food during distribution and storage process under severe high temperatures.

Levo-transposition of the Great Arteries in an Adult Patient: Management Considerations and Treatment Strategy.

Levo-transposition of the great arteries (L-TGA) is a rare congenital heart anomaly associated with the increased risk of developing heart failure (HF) as well as complete heart block at a young age. Due to limited data regarding the treatment strategy in the adult L-TGA sub-population, shared medical decision-making should occur between the patient and a team of physicians. Clinical status, age, and associated cardiac lesions or rhythm disturbances can affect patient outcomes. These factors should be considered prior to pursuing a surgical versus a medicinal approach.

Congenitally corrected transposition of the great vessels: evaluation with cardiac magnetic resonance imaging after double-switch repair. / Transposición congénitamente corregida de grandes arterias: valoración por resonancia magnética cardíaca tras corrección anatómica tipo "doble switch".

Congenitally corrected transposition of the great vessels implies double discordance: atrioventricular and ventriculoarterial. We present cardiac magnetic resonance images from a 9-year-old girl with congenitally corrected transposition of the great vessels, interventricular communication, and coarctation of the aorta who was treated with pulmonary artery banding, correction of coarctation, and posterior double switch. We also review the disease and the complications that should be evaluated after the surgical intervention.

Double switch operations: Should we perform physiologic or anatomic repair in congenitally corrected transposition of the great arteries.

The seeking for the optimal surgical treatment of congenitally corrected transposition of the great arteries (cTGA) is ongoing. Physiologic (conventional) repair approaches, leaving the morphologic right ventricle (MRV) on the systemic circulation side, cause systemic ventricle and tricuspid valve failure, particularly in the long-term. Double Switch operations (anatomic repair) were aimed to convert the morphologic left ventricle to systemic ventricle and MRV to pulmonic ventricle. Gradual improvement in the early and midterm results of double switch operations in the last 20 years rendered anatomic repair to become a preferred procedure. Thanks to the preservation of ventricular functions through anatomic repair, patients with congenitally cTGA may survive longer with normal/near normal functional capacity. However, studies with larger sample size and longer follow-up duration are required to establish a more definite judgement.

Single-Center Experience With the Senning Procedure in the Current Era.

The Senning procedure is an operative technique for atrial inversion in congenital heart anomalies. We sought to evaluate our contemporary outcomes employing this technique. A retrospective analysis of all patients who underwent the Senning procedure at our institution was performed. Hospital records were reviewed, and follow-up data were obtained to evaluate outcomes. Overall, a total of 19 patients underwent a Senning procedure between August 2005 and July 2014. Median age at repair was 594 days (range: 5 days to 15 years). Of those, 7 patients underwent a combined Senning-Rastelli operation and 10 patients underwent a double switch operation (arterial switch or atrial switch). Primary diagnosis was congenitally corrected transposition of the great arteries (cc-TGA) in 17 patients. Associated lesions included ventricular septal defect (n = 10), pulmonary stenosis or atresia (n = 7), and Ebstein׳s anomaly of the tricuspid valve (n = 4). There was an operative death (5%). In all, 2 patients required superior vena cava baffle revision in the operating room. No new pulmonary venous or systemic venous baffle obstruction was observed during follow-up. A total of 5 (26%) patients developed heart block requiring pacemaker implantation. Actuarial survival was 81% at 5 years with a median follow-up of 38 months. The 2 patients in the cc-TGA group were subsequently transplanted. Surviving patients (n = 15) are all well at the last clinical follow-up, most with normal biventricular function. In conclusion, the Senning procedure offers excellent outcomes with regard to systemic and pulmonary venous baffle patency. Results in patients with cc-TGA, however, are affected by significant early mortality after Senning-Rastelli and incidence of left ventricular dysfunction after double switch; which should be considered during patient selection and surgical planning.