Improvement in Echocardiographic and Diagnostic Biomarkers after Systemic Glucocorticoid Therapy in Infants with Pulmonary Hypertension.

OBJECTIVE: To assess the effect of treating pulmonary hypertension (PH) in infants younger than 1 year of age with systemic glucocorticoids while using echocardiographic and diagnostic biomarkers as measures of efficacy. STUDY DESIGN: A retrospective chart review was performed on 17 hospitalized infants younger than 1 year of age at St Louis Children's Hospital who received a 5- to 7-day course of systemic glucocorticoid treatment followed by a 3-week taper with no significant intracardiac shunts from January 1, 2017, to December 31, 2021. Quantitative echocardiographic indices for PH, N-terminal pro b-type natriuretic peptide, and/or b-type natriuretic peptide levels were collected before glucocorticoid treatment, after the glucocorticoid burst, and after the 21-day taper. RESULTS: Mean (±SD) gestational age was 32.1 (±5.8) weeks, 5 infants were (29%) concomitantly treated with sildenafil, and 8 were male. Twelve were classified as World Health Organization group 3 PH (71%) and 5 as World Health Organization group 1 PH. There were significant improvements 30 days after glucocorticoid initiation in b-type natriuretic peptide levels (P = .008), PCO2 (P = .03), eccentricity index (P = .005), right ventricular ejection time (P = .04), pulmonary artery acceleration time (P = .002), and pulmonary artery acceleration time-to-right ventricular ejection time ratio (P = .02). Tricuspid regurgitation velocity was not able to be assessed. There were no mortalities during the study timeline. CONCLUSIONS: In our retrospective study, systemic glucocorticoid therapy was well tolerated and appeared to be associated with significant improvement in cardiopulmonary function in infants with PH. Further prospective study in a larger sample is warranted.

Accuracy of endobronchial ultrasound (EBUS) in the staging of lung cancer - A comparison of staging EBUS with postoperative pathological nodal staging.

BACKGROUND: Endobronchial ultrasound-guided transbronchial fine-needle aspiration (EBUS-TBNA) has replaced mediastinoscopy as the preferred investigation for evaluating mediastinum in staging lung cancer. There is little evidence of mediastinal staging by EBUS-TBNA from India. OBJECTIVES: To study endobronchial ultrasound's diagnostic accuracy in staging lung cancer. METHODOLOGY: We retrospectively analysed patients operated on for lung cancer where EBUS was performed preoperatively for mediastinal staging. We compared the histological findings obtained from different mediastinal lymph nodes (LNs) by EBUS-TBNA with the pathology of the same LNs obtained after surgical dissection as the reference standard. RESULTS: Seventy-six patients underwent curative surgery for lung cancer. The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of EBUS-TBNA in predicting mediastinal metastasis were 93.9%, 40%, 99%, 80% and 94.6%, respectively. Of the 115 LNs sampled, EBUS-TBNA was false negative in six nodes, resulting in an up-staging of six patients. CONCLUSIONS: EBUS-TBNA has a high diagnostic accuracy for lung cancer staging.

A Unique High-Output Cardiac Hypertrophy Phenotype Arising From Low Systemic Vascular Resistance in Cantu Syndrome.

Background Cardiomegaly caused by left ventricular hypertrophy is a risk factor for development of congestive heart failure, classically associated with decreased systolic and/or diastolic ventricular function. Less attention has been given to the phenotype of left ventricular hypertrophy with enhanced ventricular function and increased cardiac output, which is potentially associated with high-output heart failure. Lack of recognition may pose diagnostic ambiguity and management complexities. Methods and Results We sought to systematically characterize high-output cardiac hypertrophy in subjects with Cantu syndrome (CS), caused by gain-of-function variants in ABCC9, which encodes cardiovascular KATP (ATP-sensitive potassium) channel subunits. We studied the cardiovascular phenotype longitudinally in 31 subjects with CS with confirmed ABCC9 variants (median [interquartile range] age 8 years [3-32 years], body mass index 19.9 [16.5-22.9], 16 male subjects). Subjects with CS presented with significant left ventricular hypertrophy (left ventricular mass index 86.7 [57.7-103.0] g/m2 in CS, n=30; 26.6 [24.1-32.8] g/m2 in controls, n=17; P<0.0001) and low blood pressure (systolic 94.5 [90-103] mm Hg in CS, n=17; 109 [98-115] mm Hg in controls, n=17; P=0.0301; diastolic 60 [56-66] mm Hg in CS, n=17; 69 [65-72] mm Hg in control, n=17; P=0.0063). Most (21/31) subjects with CS exhibited eccentric hypertrophy with normal left ventricular wall thickness. Congestive heart failure symptoms were evident in 4 of the 5 subjects with CS aged >40 years on long-term follow-up. Conclusions The data define the natural history of high-output cardiac hypertrophy resulting from decreased systemic vascular resistance in subjects with CS, a defining population for long-term consequences of high-output hypertrophy caused by low systemic vascular resistance, and the potential for progression to high-output heart failure.

Interventional pulmonology during COVID times: A look back at the year gone by.

Background: The COVID-19 pandemic has created an unprecedented crisis, affecting every sphere of human life. A major challenge for health care workers (HCWs) is to care for patients with a highly contagious airborne disease, while making sure of their own safety. Interventional pulmonology (IP) procedures, like bronchoscopy, are particularly risky due to significant aerosol generation. Guidelines by several scientific bodies were framed on the precautions to be taken while performing IP procedures. We evaluated the IP procedures performed during the COVID-19 pandemic, and whether the precautions adopted proved adequate in preventing transmission amongst the HCWs involved in these procedures. Method: We performed a retrospective analysis of all patients who underwent IP procedures between March 2020 and November 2020, at a tertiary cancer hospital. We also evaluated the proportion of HCWs, who were involved in these procedures, and were affected by COVID-19, through their health care records. Results: We performed a total of 506 IP procedures. Two of the 18 HCWs, working in that unit, suffered from COVID-19 and recovered after a mild illness. Three HCWs were isolated with suspected infection but proved to be negative. The procedures in our IP unit were uninterrupted for the entire duration of the study period. Conclusion: IP procedures can be safely performed even in the presence of a highly contagious viral pandemic with adequate precautions.

Vocal cord biopsy under local anesthesia, with flexible bronchoscope as an outpatient procedure, by "inside-out" technique.

BACKGROUND: Pulmonologists commonly need to take biopsies of laryngeal lesions, either found incidentally while doing bronchoscopy for other indications or while investigating patients for hoarseness of voice and cough. Biopsy of laryngeal lesions has been conventionally done under general anesthesia to provide adequate samples and minimize risks and patient discomfort. Of late, these biopsies have been done as outpatient procedures, by flexible endoscopes, under local anesthesia. However, vocal cord biopsies are often challenging due to poor patient compliance. We have tested an innovative method, which we have called the "inside-out" method, to circumvent this problem. OBJECTIVES: We aimed to analyze the feasibility, yield, and the safety of the "inside-out" technique for taking vocal cord biopsies as an outpatient procedure in awake patients. MATERIAL AND METHODS: This was a prospective observational study. Data of 38 patients with vocal cord lesions in whom the above technique was employed were analyzed. RESULTS: The procedure had a diagnostic yield of 78.9% with a sensitivity of 96.7% and a specificity of 100% for detecting malignancy or dysplasia. There were no major complications. CONCLUSIONS: The "inside-out" technique was found to be feasible and safe and with a high yield.

Clinical Comparison of I-gel and Laryngeal Mask Airway-Supreme Airway Devices During General Anaesthesia in the Paediatric Population.

OBJECTIVES: Both the Supreme Laryngeal Mask Airway (SLMA) and the I-gel (I-gel) are supraglottic airway devices (SADs) commonly used for airway management in paediatric patients. This study aims to compare the efficacy in terms of insertion and ventilation profiles of size 2 SLMA and the I-gel in anaesthetised paediatric patients. METHODS: 100 children were prospectively allocated to two groups depending upon the device inserted as SLMA (n = 50) and I-gel (n = 50). The primary outcomes were studied in terms of ease of insertion, haemodynamic changes, ventilation parameters, leak pressure and incidences of complications during general anaesthesia. RESULTS: There were no failed attempts in the insertion of the airways in either group. The SLMA was more easily inserted in the majority of cases compared to the I-gel group. The number of attempts for insertion and the time taken for insertion were comparable in the I-gel and the SLMA group (13.8462.38 vs. 14.0261.7) (P .57, .66). Securing an effective airway took <30 seconds in both the groups with an overall median duration of 15 seconds. There was no difficulty in passing the gastric tube in either group (P<.30). There was a statistical difference between the oropharyngeal seal pressure (OSP), which was 25.1861.59 and 22.1061.36 cmH2O for SLMA and I-gel, respectively (P<.001). Haemodynamic parameters after the insertion of the device were comparable, and there were no clinically important complications in the post-operative period. CONCLUSIONS: Both the devices appeared to be simple and suitable for airway management during elective surgery in paediatric patients. However, the SLMA was easily inserted with less insertion time in the majority of patients. Also, it provides higher OSP during anaesthesia and is better tolerated during emergence, with minimal risk of injury to the oropharynx.

Endobronchial capillary hemangioma a rare cause of hemoptysis.

Endobronchial capillary hemangioma is a very rare benign tumor in adults. The clinical presentation and management of adult capillary hemangiomas involving the tracheobronchial tree are not yet established. We present a case of an isolated capillary hemangioma of the right main bronchus detected during the evaluation of an adult male presented with hemoptysis.

Rapid development of pulmonary hypertension during treatment of paediatric cancer.

Paediatric pulmonary hypertension has been described as a secondary complication of multiple diseases and their treatment. Limited information exists about the relationship between pulmonary hypertension and cancer in children. A review of charts was performed in all patients treated for cancer and developed pulmonary hypertension. A total of four patients developed pulmonary hypertension during treatment of cancer. All patients had solid tumors, had echocardiographic evidence of elevated right ventricular pressures, and required intensive care stays. Treatment courses included inhaled and oral pulmonary vasodilators along with systemic steroids. Each had normalisation of echocardiograms and resolution of pulmonary symptoms. Prompt diagnosis of pulmonary hypertension and treatment with pulmonary vasodilators and steroids are considered important measures followed by chemotherapy and radiation regimens.

Learning of a Decision-Maker's Preference Zone With an Evolutionary Approach.

A new evolutionary-learning algorithm is proposed to learn a decision maker (DM)'s best solution on a conflicting multiobjective space. Given the exemplary pairwise comparisons of solutions by a DM, we learn an ideal point (for the DM) that is used to evolve toward a better set of solutions. The process is repeated to get the DM's best solution. The comparison of solutions in pairs facilitates the process of eliciting training information for the proposed learning model. Experimental study on standard multiobjective data sets shows that the proposed method accurately identifies a DM's preferred zone in relatively a few generations and with a small number of preferences. Besides, it is found to be robust to inconsistencies in the preference statements. The results obtained are validated through a variant of the established NSGA-2 algorithm.

Potts Shunt Improves Right Ventricular Function and Coupling With Pulmonary Circulation in Children With Suprasystemic Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension is a progressive disease with poor outcomes in children. Right ventricular (RV) function is the most important determinant of the prognosis. Novel application of Potts shunt between left pulmonary artery and descending aorta has been introduced in an attempt to improve the survival. However, the effect of Potts shunt creation on RV function, RV-PA coupling, and survival has not been studied. METHODS AND RESULTS: We evaluated the first 12 consecutive pediatric patients (9 male, median age 11.2 years and weight 32.8 kg) who underwent elective Potts shunt placement for suprasystemic pulmonary arterial hypertension between 2013 and 2017 with echocardiographic indices of RV function, RV work, RV-PA coupling, and pulmonary hemodynamics. Of 12 patients, 1 was excluded because of insufficient preshunt data, 2 died, 1 required lung transplant, and 8 survived for a median of 27 months postshunt. In survivors, WHO functional class significantly ( P=0.01) improved and the majority (5 of 8) came off pulmonary vasodilators at the most recent follow-up. Postshunt RV systolic function improved ( P=0.03), RV afterload decreased ( P <0.01), RV work decreased ( P=0.02), and RV-proximal PA coupling improved ( P<0.01). CONCLUSIONS: This proof of concept study shows that Potts shunt allows improvement in functional status and mid-term transplant-free survival in the majority of the recipients by improvement in RV systolic function and RV-PA coupling in children with suprasystemic pulmonary arterial hypertension.

Treatment of Pediatric Pulmonary Hypertension.

Pulmonary hypertension (PH) is an increasingly recognized problem in children, particularly within tertiary pediatric hospitals. This increase is, in large part, due to ever improving survival among previously fatal conditions, such as extreme prematurity and complicated congenital heart disease. This increased recognition has paralleled burgeoning pharmacologic and interventional PH-specific treatment options. Unfortunately, most PH-specific therapies have not been tested in children with rigorous, randomized, controlled trials. As a result, most treatment of PH in children is based upon expert consensus and practitioners' experience. In this article, we highlight some of the current and recent advances in therapies available for children with PH. The role that a Potts shunt may have in ameliorating severe PH in children is highlighted.

Glucocorticoids for treating paediatric pulmonary hypertension: a novel use for a common medication.

Laboratory investigations have shown the role of inflammation in the pathogenesis of pulmonary hypertension and improvement after anti-inflammatory drugs. Despite these observations, reports on the use of steroids to treat pulmonary hypertension in humans are absent from the literature. In this article, we report the use of glucocorticoids in the treatment of two children with pulmonary hypertension, demonstrating its potential utility.

Embryonic stem cell-derived haematopoietic progenitor cells down-regulate the CD3 ξ chain on T cells, abrogating alloreactive T cells.

Murine embryonic stem (ES) cell-derived haematopoietic progenitor cells (HPCs) engraft and populate lymphoid organs. In vivo, HPCs engraft across MHC barriers protecting donor-type allografts from rejection. However, the underlying phenomenon remains elusive. Here, we sought to determine the mechanism by which ES cell-derived HPCs regulate alloreactive T cells. We used the 2C mouse, which expresses a transgenic T-cell receptor against H2-L(d) to determine whether HPCs are deleted by cytotoxic T lymphocytes (CTLs). Previously, we reported that HPCs express MHC class I antigens poorly and do not express class II antigens. In vitro stimulated 2C CTLs failed to lyse H2-L(d) HPCs in a standard 4-hr (51) chromium release assay. Similarly, when the HPCs were tested in an ELISPOT assay measuring the release of interferon-γ by CTLs, HPCs failed to induce CTL degranulation. In addition, mice that were injected with HPCs showed a marked decrease in T-cell responses to alloantigen and CD3 stimulation, but showed a normal response to PMA/ionomycin, suggesting that HPCs impaired T-cell signalling through the T-cell receptor/CD3 complex. Here, we show that HPCs secrete arginase, an enzyme that scavenges l-arginine, leading to metabolites that down-regulate CD3 ζ chain. Indeed an arginase inhibitor partially restored expression of the CD3 ζ chain, implicating arginase 1 in the down-regulation of T cells. This previously unrecognized property of ES cell-derived HPCs could positively enhance the engraftment of ES cell-derived HPCs across MHC barriers by preventing rejection.

Iatrogenic atrioventricular reentrant tachycardia following Bjork/Fontan palliation of tricuspid atresia: Electro-anatomic mapping, ablation, review and possible mechanism.

This case report describes the successful ablation of an iatrogenic accessory pathway in a Fontan patient. A 15-year-old girl with tricuspid atresia was palliated with a Bjork modification Fontan procedure; six years later she developed supraventricular tachycardia. Electro-anatomic mapping during electrophysiology study localized a concealed iatrogenic atrioventricular accessory pathway and facilitated successful ablation using radiofrequency energy. This report reviews the reported cases of anomalous atrioventricular conduction (antegrade only, retrograde only [Hager, et al., J Thorac Cardiovasc Surg 2005;130:48-53], both [Liberman, et al., Pacing Clin Electrophysiol 2000;23:914-6]) after the Fontan/Bjork repair, outlines a potential pathophysiologic mechanism for the post-operative tachyarrhythmia and highlights the usefulness of electro-anatomic mapping in identifying unusual arrhythmias in post-operative patients with complex congenital heart disease.

Economic evaluation of an intensified disease management system for patients with type 2 diabetes.

We evaluated the effect of a disease management (DM) program on adherence with recommended laboratory tests, health outcomes, and health care expenditures for patients with type 2 diabetes. The study was a natural experiment in a primary care setting in which the intervention was available to 1 group and then compared to the experience of a matched control group. Univariate analysis and difference in differences analysis were used to test for any significant differences between the 2 groups following a 12-month intervention period. A payer perspective was used to estimate the health care cost consequences based on hospital and physician utilization weighted by Medicare prices. The results were nonsignificant at the .10 level, except for compliance with recommended tests, which showed significant results in the univariate analysis. The intervention increased compliance with testing for HbA1c, microalbuminuria, and lipids, and decreased HbA1c value and the percent of patients with HbA1c >or=9.5%. The point estimates showed small reductions in health care cost; only reductions in costs for office visits were significant at the .10 level. We concluded that while there were signs of improvement in adherence to testing, the low effectiveness may be attributed to existing diabetes management activities in this primary care setting, high compliance rates for testing at the beginning of the study, and a steep learning curve for this complex, information-technology-based DM system. The study raises questions about the incremental gains from complex systems approaches to DM and illustrates a rigorous method to assess DM programs under "real-world" conditions, with control for possible selection bias.

Mesenchymal chondrosarcoma: a series of 23 cases.

A total of 23 cases of mesenchymal chondrosarcoma were studied from the histopathology records spanning 23 years. There were 16 men and 7 women afflicted with this tumor and their mean age was 28.1 years. The radiological features, histology and treatment outcomes have been studied. Osseous and extra-osseous mesenchymal chondrosarcomas are compared and the differential diagnosis discussed.

A comparison of in vitro enamel demineralization potential of 3 orthodontic cements.

The objective of this in vitro study was to compare resistance to enamel demineralization after banding with 3 orthodontic cements. The 3 orthodontic cement groups and the nonbanded control group were evaluated for cariopreventive potential. One hundred twenty extracted human molars were selected for banding, embedded in resin blocks, and randomly assigned to the following 4 groups: zinc phosphate cement, zinc polycarboxylate cement, resin-modified glass ionomer (RMGI), and nonbanded control. Orthodontic bands were placed and cemented; specimens were stored in artificial saliva at 37 degrees C for 30 days, thermocycled for 24 hours, and then debanded with a customized band-removal device attached to a universal testing machine. The cement was hand removed, and 2 coats of nail varnish were applied to the teeth, leaving a 2 x 2-mm window exposed on the buccal surface of the mesiobuccal cusp. The teeth were stored in lactic acid-gelatin solution for 4 weeks at 37 degrees C to develop simulated white spot decalcification in the window. The teeth were subjected to dye (10% methylene blue) for 24 hours and then sectioned through the window. The depth of dye penetration was determined and used as a measure of the cariopreventive effect of the banding cement. Data were analyzed with a 1-way ANOVA and a Tukey test for the multiple comparisons. Dye penetration occurred as follows: the zinc phosphate and control groups were about the same; there was less dye penetration with the zinc polycarboxylate, and the least with the resin-modified glass ionomer. The 2 fluoride-releasing cements (zinc polycarboxylate and RMGI) demonstrated less demineralization than the zinc phosphate in vitro and might provide greater protection from demineralization around a band periphery in clinical settings.