Pulmonary valve replacement in tetralogy of Fallot - who and how?

BACKGROUND AND AIM: Pulmonary regurgitation is the most common complication in repaired tetralogy of Fallot patients. Severe chronic pulmonary regurgitation can be tolerated for decades, but if not treated, it can progress to symptomatic, irreversible right ventricular dilatation and dysfunction. We investigated clinical associations with pulmonary valve replacement among patients with significative pulmonary regurgitation and how interventional developments can change their management. METHODS: All adult patients with repaired tetralogy of Fallot who were followed at an adult CHD Clinic at a single centre from 1980 to 2022 were included on their first outpatient visit. Follow-up was estimated from the time of correction surgery until one of the following events occurred first: pulmonary valve replacement, death, loss to follow-up or conclusion of the study. RESULTS: We included 221 patients (116 males) with a median age of 19 (18-25). At a median age of 33 (10) years old, 114 (51%) patients presented significant pulmonary regurgitation. Among patients with significant pulmonary regurgitation, pulmonary valve replacement was associated with male gender, older age at surgical repair, and longer QRS duration in adulthood. Pulmonary valve replacement was performed in 50 patients, including four transcatheter pulmonary valve implantations, at a median age of 34 (14) years. CONCLUSION: Pulmonary regurgitation affects a large percentage of tetralogy of Fallot adult patients, requiring a long-term clinical and imaging follow-up. Sex, age at surgical repair and longer QRS are associated with the need of PVR among patients with significative pulmonary regurgitation. Clinical practice and current literature support TPVI as the future gold standard intervention.

New Evidence on BPA's Role in Adipose Tissue Development of Proinflammatory Processes and Its Relationship with Obesity.

Bisphenol A (BPA) is a xenobiotic with endocrine disruptor properties which interacts with various receptors, eliciting a cellular response. In the plastic industry, BPA is widely used in the production of polycarbonate and epoxy-phenolic resins to provide elastic properties. It can be found in the lining of canned foods, certain plastic containers, thermal printing papers, composite dental fillings, and medical devices, among other things. Therefore, it is a compound that, directly or indirectly, is in daily contact with the human organism. BPA is postulated to be a factor responsible for the global epidemic of obesity and non-communicable chronic diseases, belonging to the obesogenic and diabetogenic group of compounds. Hence, this endocrine disruptor may be responsible for the development of metabolic disorders, promoting in fat cells an increase in proinflammatory pathways and upregulating the expression and release of certain cytokines, such as IL6, IL1ß, and TNFα. These, in turn, at a systemic and local level, are associated with a chronic low-grade inflammatory state, which allows the perpetuation of the typical physiological complications of obesity.

Improving Lurasidone Hydrochloride's Solubility and Stability by Higher-Order Complex Formation with Hydroxypropyl-ß-cyclodextrin.

The biopharmaceutical classification system groups low-solubility drugs into two groups: II and IV, with high and low permeability, respectively. Most of the new drugs developed for common pathologies present solubility issues. This is the case of lurasidone hydrochloride-a drug used for the treatment of schizophrenia and bipolar depression. Likewise, the stability problems of some drugs limit the possibility of preparing them in liquid pharmaceutical forms where hydrolysis and oxidation reactions can be favored. Lurasidone hydrochloride presents the isoindole-1,3-dione ring, which is highly susceptible to alkaline hydrolysis, and the benzisothiazole ring, which is susceptible to a lesser extent to oxidation. Herein, we propose to study the increase in the solubility and stability of lurasidone hydrochloride by the formation of higher-order inclusion complexes with hydroxypropyl-ß-cyclodextrin. Several stoichiometric relationships were studied at between 0.5 and 3 hydroxypropyl-ß-cyclodextrin molecules per drug molecule. The obtained products were characterized, and their solubility and stability were assessed. According to the obtained results, the formation of inclusion complexes dramatically increased the solubility of the drug, and this increased with the increase in the inclusion ratio. This was associated with the loss of crystalline state of the drug, which was in an amorphous state according to infrared spectroscopy, calorimetry, and X-ray analysis. This was also correlated with the stabilization of lurasidone by the cyclodextrin inhibiting its recrystallization. Phase solubility,1H-NMR, and docking computational characterization suggested that the main stoichiometric ratio was 1:1; however, we cannot rule out a 1:2 ratio, where a second cyclodextrin molecule could bind through the isoindole-1,3-dione ring, improving its stability as well. Finally, we can conclude that the formation of higher-order inclusion complexes of lurasidone with hydroxypropyl-ß-cyclodextrin is a successful strategy to increase the solubility and stability of the drug.

The role of the hepatic factor on the improvement of arterial oxygenation after a Kawashima procedure: A case report.

BACKGROUND: Anomalies of the systemic venous return to the heart are infrequent, occurring more often in patients with congenital heart disease. CASE REPORT: We present a patient with heterotaxy, univentricular circulation, and hemiazygos return who underwent a Kawashima procedure at 3 years of age. Fourteen years later, she developed increased cyanosis and tiredness. The symptoms clearly improved after an off-pump derivation of the hepatic drainage from the common atrium to the hemiazygos system. CONCLUSIONS: This rare case report addresses the surgical challenges imposed by patients with complex congenital heart disease combined with anomalies in systemic venous return. Although improvement in arterial oxygenation after redirecting hepatic flow to the hemiazygos system in patients previously submitted to a Kawashima procedure has already been reported, the existence of a hepatic factor remains to be recognized.

New Insights on the Role of Connexins and Gap Junctions Channels in Adipose Tissue and Obesity.

Due to the inability to curb the excessive increase in the prevalence of obesity and overweight, it is necessary to comprehend in more detail the factors involved in the pathophysiology and to appreciate more clearly the biochemical and molecular mechanisms of obesity. Thus, understanding the biological regulation of adipose tissue is of fundamental relevance. Connexin, a protein that forms intercellular membrane channels of gap junctions and unopposed hemichannels, plays a key role in adipogenesis and in the maintenance of adipose tissue homeostasis. The expression and function of Connexin 43 (Cx43) during the different stages of the adipogenesis are differentially regulated. Moreover, it has been shown that cell-cell communication decreases dramatically upon differentiation into adipocytes. Furthermore, inhibition of Cx43 degradation or constitutive overexpression of Cx43 blocks adipocyte differentiation. In the first events of adipogenesis, the connexin is highly phosphorylated, which is likely associated with enhanced Gap Junction (GJ) communication. In an intermediate state of adipocyte differentiation, Cx43 phosphorylation decreases, as it is displaced from the membrane and degraded through the proteasome; thus, Cx43 total protein is reduced. Cx is involved in cardiac disease as well as in obesity-related cardiovascular diseases. Different studies suggest that obesity together with a high-fat diet are related to the production of remodeling factors associated with expression and distribution of Cx43 in the atrium.

Chylothorax in the neonate-A stepwise approach algorithm.

BACKGROUND: Chylothorax in neonates results from leakage of lymph from thoracic lymphatic ducts and is mainly congenital or posttraumatic. The clinical course of the effusion is heterogeneous, and consensus on treatment, timing, and modalities of measures has not yet been established. This review aims to present, along with levels of evidence and recommendation grades, all current therapeutic possibilities for the treatment of chylothorax in neonates. METHODS: An extensive search of publications between 1970 and 2020 was performed in the PubMed, Cochrane Database of Systematic Reviews, and UpToDate databases. A stepwise approach algorithm was proposed for both congenital and traumatic conditions to guide the clinician in a rational and systematic way for approaching the treatment of neonates with chylothorax. DISCUSSION AND CONCLUSION: The treatment strategy for neonatal chylothorax generally involves supportive care and includes drainage and procedures to reduce chyle flow. A stepwise approach starting with the least invasive method is advocated. Progression in the invasiveness of treatment options is determined by the response to previous treatments. A practical stepwise approach algorithm is proposed for both, congenital and traumatic chylothoraces.

Mobilization of an anomalous retroaortic coronary artery to prevent myocardial ischemia after aortic valve replacement.

Abnormal distribution may put coronary arteries at risk of damage during valvular surgery, especially if it is not identified during a preoperative examination. In this case report, we describe an approach to an anomalous right coronary artery during aortic valve replacement.

An Update on Connexin Gap Junction and Hemichannels in Diabetic Retinopathy.

Diabetic retinopathy (DR) is one of the main causes of vision loss in the working age population. It is characterized by a progressive deterioration of the retinal microvasculature, caused by long-term metabolic alterations inherent to diabetes, leading to a progressive loss of retinal integrity and function. The mammalian retina presents an orderly layered structure that executes initial but complex visual processing and analysis. Gap junction channels (GJC) forming electrical synapses are present in each retinal layer and contribute to the communication between different cell types. In addition, connexin hemichannels (HCs) have emerged as relevant players that influence diverse physiological and pathological processes in the retina. This article highlights the impact of diabetic conditions on GJC and HCs physiology and their involvement in DR pathogenesis. Microvascular damage and concomitant loss of endothelial cells and pericytes are related to alterations in gap junction intercellular communication (GJIC) and decreased connexin 43 (Cx43) expression. On the other hand, it has been shown that the expression and activity of HCs are upregulated in DR, becoming a key element in the establishment of proinflammatory conditions that emerge during hyperglycemia. Hence, novel connexin HCs blockers or drugs to enhance GJIC are promising tools for the development of pharmacological interventions for diabetic retinopathy, and initial in vitro and in vivo studies have shown favorable results in this regard.

ECMO POST-CARDIOTOMY, A SINGLE CENTRE EXPERIENCE.

OBJECTIVES: Our objective was to examine the results of ECMO post cardiotomy in Centro Hospitalar Universitário S. João (CHUSJ). METHODS: Between 2011 and 2019, 13 patients were cannulated for refractory cardiogenic shock post-cardiotomy; 8 (61,5%) male and 5 (38,5%) female. Patients under 18 years old were excluded. Data was collected from hospital archives concerning preoperative comorbidities, open-heart surgery procedure, dates of ECMO cannulation and decannulation, postoperative complications, hospital mortality and cause of death. Follow-up was obtained by review of the last outpatient observation. The outcomes investigated were hospital mortality and survival at 12, 36 and 60 months. RESULTS: After a median ECMO-VA therapy of 6 days (1-16 days), 7 (53,8%) patients were successfully decannulated; from these 2 succumbed from stroke and septic shock, one is still in intermediate care convalescing steadily and 4 were discharged. Overall 8 (61,5%) patients died. 5 (38,5%) survived, 4 were discharged home and 1 is still in intermediate care. Survival (after discharge) at 12, 36 and 60 months was respectively 25%, 16,7% and 8,3%. Regarding postoperative complications, reoperation for bleeding was necessary in 5 (38.5%), stroke was diagnosed in 2 (15,4%), dialysis in 6 (46,2%), leg ischemia affected 5 (38,5%) and mediastinitis occurred in 1 (7,7%). CONCLUSIONS: VA ECMO saves a life in each three patients suffering from refractory cardiogenic shock after cardiac surgery. Despite risks associated with advanced cardiopulmonary support, survivors maintain good health condition.

Unsupervised and scalable low train pathology detection system based on neural networks.

Currently, there exist different technologies applied in the world of medicine dedicated to the detection of health problems such as cancer, heart diseases, etc. However, these technologies are not applied to the detection of lower body pathologies. In this article, a Neural Network (NN)-based system capable of classifying pathologies of the lower train by the way of walking in a non-controlled scenario, with the ability to add new users without retraining the system is presented. All the signals are filtered and processed in order to extract the Gait Cycles (GCs), and those cycles are used as input for the NN. To optimize the network a random search optimization process has been performed. To test the system a database with 51 users and 3 visits per user has been collected. After some improvements, the algorithm can correctly classify the 92% of the cases with 60% of training data. This algorithm is a first approach of creating a system to make a first stage pathology detection without the requirement to move to a specific place.

THORACIC SURGERY IN A COVID-19 FRONTLINE HOSPITAL. ARE THE PATIENTS SAFE?

INTRODUCTION AND OBJECTIVES: COVID-19 pandemic forced a change in health care resources and provision due to the emergence of a new group of patients, requiring extraordinary protective measures and the adoption of new organization for the treatment of urgent or priority COVID-19 negative patients. We reviewed our practice during the first pandemic period to evaluate our surgical outcomes and identify if patients COVID-19 negative submitted to thoracic surgery had an increased risk of being infected or die. METHODS: We retrospectively reviewed our surgical results between 11th March and 15th May 2020. Thirty patients underwent thoracic surgery at the Department of Cardiothoracic Surgery of Centro Hospitalar Universitário de São João. RESULTS: None of the patients was COVID-19 positive and cross-transmission of the disease was not recognized. The majority of patients were admitted from home, with a high priority indication, namely an oncological disease. There was only one case of in-hospital mortality. CONCLUSION: During the first wave of the pandemic it was safe to be admitted and submitted to thoracic surgery at CHUSJ. Our patients, including oncological patients, received the adequate surgical treatment without an increase of risk of death or infection.

Rare cause of dynamic aortic obstruction in pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries: a case report.

A 2-month-old infant with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries developed an aneurysmatic elongation of the tricuspid valve tissue that partially closed and dynamically protruded through the ventricular septal defect, beneath the aortic valve. This rare finding caused dynamic left ventricle outflow tract obstruction and recurrent cardiac arrests and ultimately required surgical intervention.

Wearable Transcranial Ultrasound System for Remote Stimulation of Freely Moving Animal.

OBJECTIVE: Transcranial focused ultrasound (tFUS) has drawn considerable attention in the neuroscience field as a noninvasive approach to modulate brain circuits. However, the conventional approach requires the use of anesthetized or immobilized animal models, which places considerable restrictions on behavior and affects treatment. Thus, this work presents a wireless, wearable system to achieve ultrasound brain stimulation in freely behaving animals. METHODS: The wearable tFUS system was developed based on a microcontroller and amplifier circuit. Brain activity induced by tFUS was monitored through cerebral hemodynamic changes using near-infrared spectroscopy. The system was also applied to stroke rehabilitation after temporal middle cerebral artery occlusion (tMCAO) in rats. Temperature calculations and histological results showed the safety of the application even with prolonged 40 min sonication. RESULTS: The output ultrasonic wave produced from a custom PZT transducer had a central frequency of 457 kHz and peak to peak pressure of 426 kPa. The device weight was 20 g, allowing a full range of motion. The stimulation was found to induce hemodynamic changes in the sonicated area, while open-field tests showed that ultrasound applied to the ipsilateral hemisphere for 5 consecutive days after the stroke facilitated recovery. CONCLUSION: The wearable tFUS system has been designed and implemented on moving rats. The results showed the ability of device to cause both short- and long lasting effects. SIGNIFICANCE: The proposed device provides a more natural environment to investigate the effects of tFUS for behavioral and long-term studies.

Antimicrobial and Antibiofilm Capacity of Chitosan Nanoparticles against Wild Type Strain of Pseudomonas sp. Isolated from Milk of Cows Diagnosed with Bovine Mastitis.

Bovine mastitis (BM) is the most prevalent bacterial infection in the livestock sector, affecting the dairy industry greatly. The prevention and treatment of this disease is mainly made via antibiotics, but the increasing antimicrobial resistance of pathogens has affected the efficiency of conventional drugs. Pseudomonas sp. is one of the pathogens involved in this infection. The therapeutic rate of cure for this environmental mastitis-causing pathogen is practically zero, regardless of treatment. Biofilm formation has been one of the main virulence mechanisms of Pseudomonas hence presenting resistance to antibiotic therapy. We have manufactured chitosan nanoparticles (NQo) with tripolyphosphate (TPP) using ionotropic gelation. These NQo were confronted against a Pseudomonas sp. strain isolated from milk samples of cows diagnosed with BM, to evaluate their antimicrobial and antibiofilm capacity. The NQo showed great antibacterial effect in the minimum inhibitory concentrations (MIC), minimum bactericidal concentration (MBC) and disk diffusion assays. Using sub lethal concentrations, NQo were tested for inhibition of biofilm formation. The results show that the nanoparticles exhibited biofilm inhibition and were capable of eradicate pre-existing mature biofilm. These findings indicate that the NQo could act as a potential alternative to antibiotic treatment of BM.