Revival of Brock's Operation for Intermediary Palliation of Fallot's Tetralogy in Children Anatomically Unsuitable for One-Stage Total Correction of the Anomaly: Interim Results of Two Cases.

One-stage total correction is known to be anatomically unsuitable for correcting tetralogy of fallot (TOF) in a certain proportion of children. Surgeons are thus faced with dilemmas regarding which preliminary operation for the anomaly to do first. Brock's primary postulation suggests that pulmonary trunk and annulus enlargement leading to the correction of the outflow obstruction will favor the subsequent total correction. In line with this, the current article presents two patients who were 6 months and 5 years old. The first patient underwent primary Brock's operation while the second patient had a blocked modified Blalock-Taussig's shunt (MBTS) done off-pump. Following the discontinuation of anti-platelet medications, the MBTS blocked and the patient was subsequently considered for secondary Brock's operation. The outcome of both procedures involved the patients' discharge with uneventful hospital stays and regular follow-ups at specified intervals. Thus, Brock's operation is an excellent preliminary palliative procedure for one-stage total correction of TOF. There is a need to revive 'Brock's procedure' for patients with TOF and poor pulmonary artery anatomy as the procedure of choice. The first direct intra-cardiac operation aimed at directly addressing the pathological anatomy on its Diamond Jubilee Year.

IL-38 blockade induces anti-tumor immunity by abrogating tumor-mediated suppression of early immune activation.

Immune checkpoint inhibitors that overcome T cell suppressive mechanisms in tumors have revolutionized the treatment of cancer but are only efficacious in a small subset of patients. Targeting suppressive mechanisms acting on innate immune cells could significantly improve the incidence of clinical response by facilitating a multi-lineage response against the tumor involving both adaptive and innate immune systems. Here, we show that intra-tumoral interleukin (IL)-38 expression is a feature of a large frequency of head and neck, lung and cervical squamous cancers and correlates with reduced immune cell numbers. We generated IMM20324, an antibody that binds human and mouse IL-38 proteins and inhibits the binding of IL-38 to its putative receptors, interleukin 1 receptor accessory protein-like 1 (IL1RAPL) and IL-36R. In vivo, IMM20324 demonstrated a good safety profile, delayed tumor growth in a subset of mice in an EMT6 syngeneic model of breast cancer, and significantly inhibited tumor expansion in a B16.F10 melanoma model. Notably, IMM20324 treatment resulted in the prevention of tumor growth following re-implantation of tumor cells, indicating the induction of immunological memory. Furthermore, exposure of IMM20324 correlated with decreased tumor volume and increased levels of intra-tumoral chemokines. Together, our data suggest that IL-38 is expressed in a high frequency of cancer patients and allows tumor cells to suppress anti-tumor immunity. Blockade of IL-38 activity using IMM20324 can re-activate immunostimulatory mechanisms in the tumor microenvironment leading to immune infiltration, the generation of tumor-specific memory and abrogation of tumor growth.

Mid-Term Outlook Following Modified Senning's Operation for the Correction of Transposition of the Great Arteries: A Case Series and Review of Literature.

At the time of writing, two patients who underwent modified Senning's operation (MSO) for the treatment of transposition of great arteries (TGAs) were followed up. At the time of surgery, the patients were three months and 15 years old, respectively. The duration of the follow-up was three years, during which there was a good prognosis, and hence no further invasive treatments were required. There was normal functioning of the right ventricle (RV) in both patients, with the exception of a minor baffle leak in the three-month-old patient. At the annual three-year follow-up, the tricuspid regurgitation (systemic atrioventricular valve) status was moderate in the three-year-old child and mild in the 18-year-old girl. Both patients maintained sinus rhythm and are assigned classification as New York Heart Association (NYHA) Classes I and II. This study aims to assess the midterm outlook after MSO in order to identify and manage future long-term complications. Our report shows a positive outcome in terms of survival and functional activities among children with d-TGA; however, there is a strong need for future research to evaluate the prognosis in the long term (LT) and to assess the functioning of RV.

Utility of Conventional but Late Pulmonary Artery Banding in Complex Cyanotic Congenital Heart Disease in a Toddler - A Single Case Scenario.

Newborns with untreated single ventricles develop pulmonary vascular diseases early in their lives. At that age, during the first eight weeks after birth, clinicians perform pulmonary artery (PA) banding to reduce the blood flow to the lung, decreasing the likelihood of future high vascular resistance or pressure. PA banding is also considered an initial stage in the process of single ventricle palliation procedures. We report a case of a 16-month-old toddler (7 kg) with room air saturation of 82%, diagnosed with tricuspid valve atresia, large atrial and ventricular septal defect, and hypoplastic right ventricle with severe pulmonary arterial hypertension. The baby underwent a successful surgical procedure of PA banding and was discharged after 13 days of hospital stay with a room air saturation of 89%. This case highlighted the benefit of PA banding beyond the stipulated period.

Detecting and Quantifying Residual Intracardiac Shunts Using Oximetric Step-Up Methods: A Prospective Observational Study.

Background & aims  Intracardiac shunts are abnormal channels of blood circulation within the heart that develop either as an additional blood flow pathway or as a replacement for the normal channels of blood circulation. They are the commonest types of congenital heart defects. Various methods are available in the present times to identify, localize or quantify left-to-right intracardiac shunts. Methods may vary in sensitivity, indicators, or types of equipment available. One such method used in almost all cardiac centers for a long time has been oximetry run to detect step-up differences in oxygen saturation values. In the oximetry run the main approach to detect and estimate the left-to-right (L-->R) shunts requires the oxygen concentration expressed as a proportion of saturation to be evaluated in blood samples which are obtained from the right atrium (RA) and pulmonary artery (PA), respectively. A left-to-right shunt can be considered if there is a significant increase (step-up) in blood saturation. A significant step-up is defined as a substantial rise in blood oxygen content or saturation that is higher than normal values. Methods  Using a prospective observational design, this article investigates the application of the step-up method in detecting intracardiac shunts. The study was conducted between 2021 and 2022 on 35 pediatric cardiac patients (males/females, 24/11) diagnosed with post-tricuspid shunts. The pulmonary artery and right atrium were sampled before and after cardiopulmonary bypass surgery and analyzed using a blood gas test. As a result, nearly 91% of the patients had a saturation below 8%. However, the difference between PA oxygen saturation (SO2) & RASO2 before and after surgery was significant. As a result, the difference in O2 saturation helped detect the residual ventricular septal defect (VSD) after the surgery. Results  There were no deaths or complications in this study. There were no re-interventions for post-tricuspid shunt surgery, though one patient had a step-up of >15% and residual VSD status was moderate to large on two-dimensional (2D) echocardiography. Conclusion A combination of physical findings, chest radiography, electrocardiogram (ECG), and echocardiography is routinely done for all these patients undergoing pediatric cardiac surgery. Echocardiography can detect the occurrence of shunt but does not calculate the shunt ratio. Transesophageal or epicardial echocardiography is the standard of care but has its limitations like perception difference between the operating surgeon and the person performing echocardiography. In this study, we have added an oximetry analysis of blood-gas samples before and after surgery and compared it to 2D echocardiography to test the validation of oximetry in isolation and comparison to 2D echocardiography.

Midterm postoperative outcomes of different types of surgical reconstruction of sinus venosus atrial septal defects with anomalous pulmonary venous connection: The Results of Prospective Cohort Study.

Background and Aims: Sinus venosus atrial septal defects (SVASDs) constitute a substantial part of atrial septal defects and are usually characterized by anomalous pulmonary venous connection (APVC), causing complications like sinus node dysfunction and arrhythmias. Several surgical approaches are used for treating SVASDs in pediatric patients, including single- and two-patch techniques. The study aimed to prospectively evaluate and compare the safety and efficacy of these two methods with different follow-up periods. Methods: Ten patients aged 1-8 years with SVASDs and partial APVC were enrolled in the study at Bhanubhai and Madhuben Patel Cardiac Centre, Karamsad, India, between December 2018 and October 2021. The single-patch (sandwich-patch) technique was used in two patients, whereas the two-patch (dual-patch) technique with autologous pericardium was used in seven. Safety was assessed as the absence of complications in the follow-up periods of 6 months, 1, and 2 years, whereas efficacy was estimated by the preserved sinus rhythm and the development of arrhythmias. Electrocardiographic and echocardiographic methods were used to evaluate both parameters. Results: No deaths, reoperations, pulmonary vein, and superior vena cava (SVC) stenosis or phrenic nerve palsy were observed among the 10 patients in the three follow-up periods. Sinus rhythm was arrested in two of the seven patients who underwent two-patch repair, whereas no rhythm disturbances occurred in those who underwent single-patch repair. Conclusion: Both techniques used in SVASD repair with autologous pericardium proved to cause the smaller rate of complications in midterm postsurgical phase. However, there is a potentially great risk of the development of sinus node malfunction after the application of the two-patch technique. Therefore, methods avoiding sinus node interference are preferred in patients with partial APVC involving SVC.

Perioperative Management of a Patient With Left Ventricular Free Wall Rupture After Myocardial Infarction: A Rare Case Scenario.

Myocardial infarction (MI) is typically followed by numerous lethal complications. One such complication is left ventricular free wall rupture (LVFWR). We present the case of a middle-aged hypertensive patient who had a history of unstable angina for seven days. He presented to the emergency room with chest pain, dyspnea, and unstable vital parameters. Clinical signs, electrocardiography, and echocardiography raised the suspicion of left ventricular free wall rupture with ST-segment elevation inferior wall and lateral wall MI. As a result, the patient received aggressive resuscitative measures. Later, he underwent surgical repair for cardiac rupture via cardiopulmonary bypass. Finally, the patient was discharged from the hospital on the 10th postoperative day. The window period from the onset of cardiac wall rupture to patient admission to the operating room is crucial. This case report highlights that a high index of suspicion for left ventricle free wall rupture should be considered for a patient presenting with MI and cardiogenic shock. Timely diagnosis and quick surgical intervention can deter complications and save the patient.

On-Pump Bidirectional Glenn Shunt Compared to Off-Pump Shunt Is a Better Influencing Determinant of Perioperative Morbidity During Palliation of Univentricular Heart: Compilation of Two Cases.

The bidirectional Glenn (BDG) or hemi-Fontan technique, performed under cardiopulmonary bypass (CPB) and often utilized as first-stage palliation for various cyanotic congenital heart diseases, as a part of the single-ventricle repair is associated with adverse side effects and high expenditures. Previous studies have shown that BDG is safe even without CPB, which thus necessitates further investigation. This manuscript presents the case of two patients with complex cyanotic congenital heart diseases. The first case was an 11-month-old baby who presented with fever, cough, and cold, while the second case was a two-year-old baby who was underweight due to poor feeding status. Both patients underwent a BDG and main pulmonary artery partial ligation following the requisite preoperative medical evaluations on CPB. Moreover, case 1 had atrial septectomy, while case 2 had significant aortopulmonary collateral arteries ligation. Both patients were discharged following an uneventful postoperative outcome. We found that an adequate selection of patients for the BDG procedure, with or without CPB, could lead to identical postoperative outcomes with regard to mortality, morbidity, and supply usage.

Higher pulmonary vein index on computed angiography and optimum surgical resection ensures smooth postoperative recovery in Fallot's tetralogy: Special emphasis on indices of evaluation and Monocusp preparation.

Tetralogy of Fallot (TOF) is a common cyanotic congenital heart disease. Its surgical correction requires ventricular septal defect (VSD) closure and right ventricular outflow tract obstruction (RVOTO) relief, with transannular patch enlargement (TAPE) of the pulmonary valve. The first successful repair of TOF was reported in 1954 and consisted of closure of the VSD through a large right ventriculotomy, and RVOTO relief with TAPE of the pulmonary valve. To predict the intraoperative requirements and postoperative course of patients with this condition, various evaluation indices are available that can provide a good indication of patient prognosis. We performed this study in a male child (age, 1 year, 9 months; weight 8.5 kgs.) who underwent intracardiac repair for TOF as a primary procedure. We calculated the pulmonary vein index (PVI), McGoon ratio, and Nakata index. The McGoon ratio was 1.97, Nakata index was 539.22 mm2/m2, and PVI was 368.12 mm2/m2. The child had an uneventful post-operative course with no symptoms of low cardiac output syndrome. He was ventilated for 122 h. The length of intensive care unit and hospital stays were 11 and 14 days, respectively. The PVI is a novel indicator offering prognostic indications for pediatric cardiac patients who have undergone surgical correction of TOF.

Hand-Made Polytetrafluoroethylene Tricuspid-Valved Conduit for Surgical Reconstruction of the Right Ventricular Outflow Tract in a Child With Truncus Arteriosus.

Although a new right ventricle outflow can be introduced during pulmonary artery reconstruction, it is a suboptimal option as the valved conduits that mimic the natural right ventricular outflow do not grow, and a surgical conduit replacement cannot be averted. This study reported the implementation of hand-made polytetrafluoroethylene (PTFE) tricuspid-valved conduits to rebuild the right ventricular outflow tract in toddlers with truncus arteriosus and risk factors for earlier conduit explant. Herein, we described a case report of a 9-month-old toddler diagnosed in November 2021 with truncus arteriosus type I with ventricular septal defect (VSD) and severe pulmonary arterial hypertension, who has been successfully discharged 20-days postoperative surgical reconstruction with good bi-ventricular functions. Hand-made PTFE tricuspid-valved conduits are efficient in the reconstruction process of the right ventricular outflow tract in children with truncus arteriosus. The conduits are cheap, easily available, and lack potential sensitization.

IMM-BCP-01, a patient-derived anti-SARS-CoV-2 antibody cocktail, is active across variants of concern including Omicron BA.1 and BA.2.

Monoclonal antibodies are an efficacious therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, rapid viral mutagenesis led to escape from most of these therapies, outlining the need for an antibody cocktail with a broad neutralizing potency. Using an unbiased interrogation of the memory B cell repertoire of patients with convalescent COVID-19, we identified human antibodies with broad antiviral activity in vitro and efficacy in vivo against all tested SARS-CoV-2 variants of concern, including Delta and Omicron BA.1 and BA.2. Here, we describe an antibody cocktail, IMM-BCP-01, that consists of three patient-derived broadly neutralizing antibodies directed at nonoverlapping surfaces on the SARS-CoV-2 Spike protein. Two antibodies, IMM20184 and IMM20190, directly blocked Spike binding to the ACE2 receptor. Binding of the third antibody, IMM20253, to its cryptic epitope on the outer surface of RBD altered the conformation of the Spike Trimer, promoting the release of Spike monomers. These antibodies decreased Omicron SARS-CoV-2 infection in the lungs of Syrian golden hamsters in vivo and potently induced antiviral effector response in vitro, including phagocytosis, ADCC, and complement pathway activation. Our preclinical data demonstrated that the three-antibody cocktail IMM-BCP-01 could be a promising means for preventing or treating infection of SARS-CoV-2 variants of concern, including Omicron BA.1 and BA.2, in susceptible individuals.

Successful Repair of Cor Triatriatum Sinistrum in Childhood: A Single-Institution Experience of Two Cases.

Cor triatriatum is a rare structural congenital cardiac anomaly in which one of the atria chambers is anatomically divided. If left untreated, cor triatriatum can eventually lead to heart failure. This case report describes our experience with two pediatric patients (a three-year-old girl and an 11-month-old male infant) who underwent surgical correction of cor triatriatum. Both patients underwent excision of the cor triatriatum membrane via cardiopulmonary bypass and had an uneventful postoperative recovery with good outcomes. Surgical repair of cor triatriatum sinister provides satisfactory short-term and long-term outcomes with a low risk of requiring additional intervention.

Perioperative Management of Scimitar Syndrome Mimicking Total Anomalous Pulmonary Venous Return Posing a Diagnostic Dilemma: A Compilation of Two Cases.

The low prevalence of scimitar syndrome along with its varied clinical presentation poses a diagnostic dilemma to the treating clinicians. It usually falls under a large spectrum of conditions called venolobar syndrome. Scimitar involves the partial venous drainage of the right lung to the inferior vena cava (IVC). We share our experience of two cases that were diagnosed as partial anomalous pulmonary venous connection/drainage (PAPVC/PAPVD) on echocardiography but CT scan revealed the underlying scimitar syndrome. Perioperative pulmonary arterial hypertension, intraoperative ventilation strategies for managing associated lung hypoplasia, and postoperative right ventricular dysfunction are a few challenges faced in the perioperative period.

Unbiased interrogation of memory B cells from convalescent COVID-19 patients reveals a broad antiviral humoral response targeting SARS-CoV-2 antigens beyond the spike protein.

Patients who recover from SARS-CoV-2 infections produce antibodies and antigen-specific T cells against multiple viral proteins. Here, an unbiased interrogation of the anti-viral memory B cell repertoire of convalescent patients has been performed by generating large, stable hybridoma libraries and screening thousands of monoclonal antibodies to identify specific, high-affinity immunoglobulins (Igs) directed at distinct viral components. As expected, a significant number of antibodies were directed at the Spike (S) protein, a majority of which recognized the full-length protein. These full-length Spike specific antibodies included a group of somatically hypermutated IgMs. Further, all but one of the six COVID-19 convalescent patients produced class-switched antibodies to a soluble form of the receptor-binding domain (RBD) of S protein. Functional properties of anti-Spike antibodies were confirmed in a pseudovirus neutralization assay. Importantly, more than half of all of the antibodies generated were directed at non-S viral proteins, including structural nucleocapsid (N) and membrane (M) proteins, as well as auxiliary open reading frame-encoded (ORF) proteins. The antibodies were generally characterized as having variable levels of somatic hypermutations (SHM) in all Ig classes and sub-types, and a diversity of VL and VH gene usage. These findings demonstrated that an unbiased, function-based approach towards interrogating the COVID-19 patient memory B cell response may have distinct advantages relative to genomics-based approaches when identifying highly effective anti-viral antibodies directed at SARS-CoV-2.

Measurement of Pro-Islet Amyloid Polypeptide (1-48) in Diabetes and Islet Transplants.

Context: Islet amyloid is a feature of ß-cell failure in type 2 diabetes (T2D) and type 1 diabetes (T1D) recipients of islet transplants. Islet amyloid contains islet amyloid polypeptide (IAPP; amylin), a circulating peptide that is produced in ß cells by processing of its precursor, proIAPP1-67, via an intermediate form, proIAPP1-48. Elevated proinsulin to C-peptide ratios in the plasma of persons with diabetes suggest defects in ß-cell prohormone processing. Objective: Determine whether plasma levels of precursor forms of IAPP are elevated in diabetes. Design, Setting, and Patients: We developed an immunoassay to detect proIAPP1-48 in human plasma, and we determined the ratio of proIAPP1-48 to mature IAPP in subjects with T1D, T2D, recipients of islet transplants, and healthy controls. Results: The proIAPP1-48 immunoassay had a limit of detection of 0.18 ± 0.06 pM and cross-reactivity with intact proIAPP1-67 <15%. Healthy individuals had plasma concentrations of proIAPP1-48 immunoreactivity of 1.5 ± 0.2 pM and a proIAPP1-48 to total IAPP ratio of 0.28 ± 0.03. Plasma concentrations of proIAPP1-48 immunoreactivity were not significantly different in subjects with T2D but were markedly increased in T1D recipients of islet transplants. Children and adults with T1D had reduced mature IAPP levels relative to age-matched controls but an elevated ratio of proIAPP1-48 to total IAPP. Conclusion: The ß cells in T1D and islet transplants have impaired processing of the proIAPP1-48 intermediate. The ratio of proIAPP1-48-to-IAPP immunoreactivity may have value as a biomarker of ß-cell stress and dysfunction.