Capacity building for pediatric neuro-oncology in Pakistan- a project by my child matters program of Foundation S.

Introduction: Initiated in June 2019, this collaborative effort involved 15 public and private sector hospitals in Pakistan. The primary objective was to enhance the capacity for pediatric neuro-oncology (PNO) care, supported by a My Child Matters/Foundation S grant. Methods: We aimed to establish and operate Multidisciplinary Tumor Boards (MTBs) on a national scale, covering 76% of the population (185.7 million people). In response to the COVID-19 pandemic, MTBs transitioned to videoconferencing. Fifteen hospitals with essential infrastructure participated, holding monthly sessions addressing diagnostic and treatment challenges. Patient cases were anonymized for confidentiality. Educational initiatives, originally planned as in-person events, shifted to a virtual format, enabling continued implementation and collaboration despite pandemic constraints. Results: A total of 124 meetings were conducted, addressing 545 cases. To augment knowledge, awareness, and expertise, over 40 longitudinal lectures were organized for healthcare professionals engaged in PNO care. Additionally, two symposia with international collaborators and keynote speakers were also held to raise national awareness. The project achieved significant milestones, including the development of standardized national treatment protocols for low-grade glioma, medulloblastoma, and high-grade glioma. Further protocols are currently under development. Notably, Pakistan's first pediatric neuro-oncology fellowship program was launched, producing two graduates and increasing the number of trained pediatric neuro-oncologists in the country to three. Discussion: The initiative exemplifies the potential for capacity building in PNO within low-middle income countries. Success is attributed to intra-national twinning programs, emphasizing collaborative efforts. Efforts are underway to establish a national case registry for PNO, ensuring a comprehensive and organized approach to monitoring and managing cases. This collaborative initiative, supported by the My Child Matters/Foundation S grant, showcases the success of capacity building in pediatric neuro-oncology in low-middle income countries. The establishment of treatment protocols, fellowship programs, and regional tumor boards highlights the potential for sustainable improvements in PNO care.

Impact of Stent Types on In-Hospital Outcomes of Patients With Cancer Undergoing Percutaneous Coronary Intervention: A Nationwide Analysis.

BACKGROUND: Cardiovascular disease and cancer frequently coexist, and patients with cancer are at increased risk of cardiovascular events, including myocardial infarction and stroke. However, the impact of stent types on in-hospital outcomes of patients with malignancy is largely unknown. METHODS: Patients with concomitant diagnosis of cancer undergoing PCI between January 2005 and December 2014 were identified in the National Inpatient Sample. They were then categorized into those who have undergone coronary stenting with bare-metal stent (BMS) or drug-eluting stent (DES). Primary outcomes were in-hospital mortality and stent thrombosis. Adjusted and unadjusted analysis was employed on appropriate variables of interest. RESULTS: 8755 patients were included in the BMS group and 11,611 patients in the DES group. Following propensity matching, 4313 patients were randomly selected in both groups using a 1:1 ratio. There was high use of BMS stent in cancer patient (BMS 43.0%, DES 57.0%) compared to general population (BMS 23.2%, DES 76.8%). When comparing BMS to DES group, there was no statistically significant difference in mortality (4.7% vs. 3.8%, p = 0.097), acute kidney injury (11.3% vs. 10.6%, p = 0.425), bleeding complications (3.50% vs. 3.45%, p = 0.914), and length of hospital stay (5.4% vs. 5.2%, p = 0.119). However, an increased incidence of stent thrombosis was observed in the DES group (4.26% vs. 3.01%, p = 0.002). CONCLUSION: A higher incidence of BMS placement was noted in patients with cancer than in the general population. Paradoxically there was a high incidence of stent thrombosis in the DES group without increasing mortality.

A Simple Percutaneous Retrieval Technique for an Embolized Watchman Left Atrial Appendage Closure Device in the Thoracic Aorta Using a Homemade Snare.

A 60-year old male with paroxysmal atrial fibrillation underwent a combined procedure of left atrial appendage occlusion and pulmonary vein isolation. However, an acute intraprocedural 24-mm Watchman device dislodgement occurred, and thus a decision for urgent surgery was made. However, it was noted during the surgery that the device had migrated further to the descending aorta, just distal to the left subclavian artery. Since a right sternotomy access for retrieval was not feasible, a percutaneous approach was justified. A homemade snare was created using a combination of a long sheath, J-wire, and a regular snare, and the device was successfully retrieved without significant difficulty.

1-Year COMBO stent outcomes stratified by the PARIS bleeding prediction score: From the MASCOT registry.

BACKGROUND: The COMBO stent is a biodegradable-polymer sirolimus-eluting stent with endothelial progenitor cell capture technology for faster endothelialization. OBJECTIVE: We analyzed COMBO stent outcomes in relation to bleeding risk using the PARIS bleeding score. METHODS: MASCOT was an international registry of all-comers undergoing attempted COMBO stent implantation. We stratified patients as low bleeding-risk (LBR) for PARIS score ≤ 3 and intermediate-to-high (IHBR) for score > 3 based on baseline age, body mass index, anemia, current smoking, chronic kidney disease and need for triple therapy. Primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, myocardial infarction (MI) not clearly attributed to a non-target vessel or clinically-driven target lesion revascularization (TLR). Bleeding was adjudicated using the Bleeding Academic Research Consortium (BARC) definition. Dual antiplatelet therapy (DAPT) cessation was independently adjudicated. RESULTS: The study included 56% (n = 1270) LBR and 44% (n = 1009) IHBR patients. Incidence of 1-year TLF was higher in IHBR patients (4.1% vs. 2.6%, p = 0.047) driven by cardiac death (1.7% vs. 0.7%, p = 0.029) with similar rates of MI (1.8% vs. 1.1%, p = 0.17), TLR (1.5% vs. 1.6%, p = 0.89) and definite/ probable stent thrombosis (1.2% vs. 0.6%, p = 0.16). Incidence of 1-year major BARC 3 or 5 bleeding was significantly higher in IHBR patients (2.3% vs. 0.9%, p = 0.0094), as was the incidence of DAPT cessation (29.3% vs. 22.8%, p < 0.01), driven by physician-guided discontinuation. CONCLUSIONS: Patients with intermediate-to-high PARIS bleeding risk in the MASCOT registry experienced greater incidence of 1-year TLF, major bleeding and DAPT cessation than LBR patients, without significant differences in stent thrombosis.

Device sizing for transcatheter closure of ruptured sinus of Valsalva as per echocardiography color Doppler turbulent flow jet diameter.

Rupture of sinus of Valsalva (SV) is a rare occurrence with a wide spectrum of presentation, ranging from an asymptomatic murmur to cardiogenic shock or even sudden cardiac death. We hereby report a case which was successfully closed by transcatheter technique. In this case, ruptured SV was entered from the aorta, an arteriovenous loop was created and device was implanted using a venous approach. The procedure was safe, effective and uncomplicated, obviating the need for surgery. In this case, the authors report for the first time the use of echo color Doppler turbulent flow jet diameter as a reference value for sizing the device.

Detection of lung cancer using weighted digital analysis of breath biomarkers.

BACKGROUND: A combination of biomarkers in a multivariate model may predict disease with greater accuracy than a single biomarker employed alone. We developed a non-linear method of multivariate analysis, weighted digital analysis (WDA), and evaluated its ability to predict lung cancer employing volatile biomarkers in the breath. METHODS: WDA generates a discriminant function to predict membership in disease vs no disease groups by determining weight, a cutoff value, and a sign for each predictor variable employed in the model. The weight of each predictor variable was the area under the curve (AUC) of the receiver operating characteristic (ROC) curve minus a fixed offset of 0.55, where the AUC was obtained by employing that predictor variable alone, as the sole marker of disease. The sign (+/-) was used to invert the predictor variable if a lower value indicated a higher probability of disease. When employed to predict the presence of a disease in a particular patient, the discriminant function was determined as the sum of the weights of all predictor variables that exceeded their cutoff values. The algorithm that generates the discriminant function is deterministic because parameters are calculated from each individual predictor variable without any optimization or adjustment. We employed WDA to re-evaluate data from a recent study of breath biomarkers of lung cancer, comprising the volatile organic compounds (VOCs) in the alveolar breath of 193 subjects with primary lung cancer and 211 controls with a negative chest CT. RESULTS: The WDA discriminant function accurately identified patients with lung cancer in a model employing 30 breath VOCs (ROC curve AUC=0.90; sensitivity=84.5%, specificity=81.0%). These results were superior to multilinear regression analysis of the same data set (AUC=0.74, sensitivity=68.4, specificity=73.5%). WDA test accuracy did not vary appreciably with TNM (tumor, node, metastasis) stage of disease, and results were not affected by tobacco smoking (ROC curve AUC=0.92 in current smokers, 0.90 in former smokers). WDA was a robust predictor of lung cancer: random removal of 1/3 of the VOCs did not reduce the AUC of the ROC curve by >10% (99.7% CI). CONCLUSIONS: A test employing WDA of breath VOCs predicted lung cancer with accuracy similar to chest computed tomography. The algorithm identified dependencies that were not apparent with traditional linear methods. WDA appears to provide a useful new technique for non-linear multivariate analysis of data.

Prediction of lung cancer using volatile biomarkers in breath.

BACKGROUND: Normal metabolism generates several volatile organic compounds (VOCs) that are excreted in the breath (e.g. alkanes). In patients with lung cancer, induction of high-risk cytochrome p450 genotypes may accelerate catabolism of these VOCs, so that their altered abundance in breath may provide biomarkers of lung cancer. METHODS: VOCs in 1.0 L alveolar breath were analyzed in 193 subjects with primary lung cancer and 211 controls with a negative chest CT. Subjects were randomly assigned to a training set or to a prediction set in a 2:1 split. A fuzzy logic model of breath biomarkers of lung cancer was constructed in the training set and then tested in subjects in the prediction set by generating their typicality scores for lung cancer. RESULTS: Mean typicality scores employing a 16 VOC model were significantly higher in lung cancer patients than in the control group (p<0.0001 in all TNM stages). The model predicted primary lung cancer with 84.6% sensitivity, 80.0% specificity, and 0.88 area under curve (AUC) of the receiver operating characteristic (ROC) curve. Predictive accuracy was similar in TNM stages 1 through 4, and was not affected by current or former tobacco smoking. The predictive model achieved near-maximal performance with six breath VOCs, and was progressively degraded by random classifiers. Predictions with fuzzy logic were consistently superior to multilinear analysis. If applied to a population with 2% prevalence of lung cancer, a screening breath test would have a negative predictive value of 0.985 and a positive predictive value of 0.163 (true positive rate =0.277, false positive rate =0.029). CONCLUSIONS: A two-minute breath test predicted lung cancer with accuracy comparable to screening CT of chest. The accuracy of the test was not affected by TNM stage of disease or tobacco smoking. Alterations in breath VOCs in lung cancer were consistent with a non-linear pathophysiologic process, such as an off-on switch controlling high-risk cytochrome p450 activity. Further research is needed to determine if detection of lung cancer with this test will reduce mortality.

Volatile biomarkers of pulmonary tuberculosis in the breath.

Pulmonary tuberculosis may alter volatile organic compounds (VOCs) in breath because Mycobacteria and oxidative stress resulting from Mycobacterial infection both generate distinctive VOCs. The objective of this study was to determine if breath VOCs contain biomarkers of active pulmonary tuberculosis. Head space VOCs from cultured Mycobacterium tuberculosis were captured on sorbent traps and assayed by gas chromatography/mass spectroscopy (GC/MS). One hundred and thirty different VOCs were consistently detected. The most abundant were naphthalene, 1-methyl-, 3-heptanone, methylcyclododecane, heptane, 2,2,4,6,6-pentamethyl-, benzene, 1-methyl-4-(1-methylethyl)-, and cyclohexane, 1,4-dimethyl-. Breath VOCs were assayed by GC/MS in 42 patients hospitalized for suspicion of pulmonary tuberculosis and in 59 healthy controls. Sputum cultures were positive for Mycobacteria in 23/42 and negative in19/42 patients. Breath markers of oxidative stress were increased in all hospitalized patients (p<0.04). Pattern recognition analysis and fuzzy logic analysis of breath VOCs independently distinguished healthy controls from hospitalized patients with 100% sensitivity and 100% specificity. Fuzzy logic analysis identified patients with positive sputum cultures with 100% sensitivity and 100% specificity (95.7% sensitivity and 78.9% specificity on leave-one-out cross-validation); breath VOC markers were similar to those observed in vitro, including naphthalene, 1-methyl- and cyclohexane, 1,4-dimethyl-. Pattern recognition analysis identified patients with positive sputum cultures with 82.6% sensitivity (19/23) and 100% specificity (18/18), employing 12 principal components from 134 breath VOCs. We conclude that volatile biomarkers in breath were sensitive and specific for pulmonary tuberculosis: the breath test distinguished between "sick versus well" i.e. between normal controls and patients hospitalized for suspicion of pulmonary tuberculosis, and between infected versus non-infected patients i.e. between those whose sputum cultures were positive or negative for Mycobacteria.