Computer-aided diagnosis for World Health Organization-defined chest radiograph primary-endpoint pneumonia in children.

BACKGROUND: The chest radiograph is the most common imaging modality to assess childhood pneumonia. It has been used in epidemiological and vaccine efficacy/effectiveness studies on childhood pneumonia. OBJECTIVE: To develop computer-aided diagnosis (CAD4Kids) for chest radiography in children and to evaluate its accuracy in identifying World Health Organization (WHO)-defined chest radiograph primary-endpoint pneumonia compared to a consensus interpretation. MATERIALS AND METHODS: Chest radiographs were independently evaluated by three radiologists based on WHO criteria. Automatic lung field segmentation was followed by manual inspection and correction, training, feature extraction and classification. Radiographs were filtered with Gaussian derivatives on multiple scales, extracting texture features to classify each pixel in the lung region. To obtain an image score, the 95th percentile score of the pixels was used. Training and testing were done in 10-fold cross validation. RESULTS: The radiologist majority consensus reading of 858 interpretable chest radiographs included 333 (39%) categorised as primary-endpoint pneumonia, 208 (24%) as other infiltrate only and 317 (37%) as no primary-endpoint pneumonia or other infiltrate. Compared to the reference radiologist consensus reading, CAD4Kids had an area under the receiver operator characteristic (ROC) curve of 0.850 (95% confidence interval [CI] 0.823-0.876), with a sensitivity of 76% and specificity of 80% for identifying primary-endpoint pneumonia on chest radiograph. Furthermore, the ROC curve was 0.810 (95% CI 0.772-0.846) for CAD4Kids identifying primary-endpoint pneumonia compared to other infiltrate only. CONCLUSION: Further development of the CAD4Kids software and validation in multicentre studies are important for future research on computer-aided diagnosis and artificial intelligence in paediatric radiology.

Vanishing white matter disease imaged over 3 years.

Childhood ataxia and central nervous system hypomyelination (CACH), also known as 'vanishing white matter disease' (VWM), is a leukoencephalopathy with autosomal recessive inheritance. It is characterised by normal psychomotor development initially, with an onset of neurological deterioration that follows a chronic and progressive course. Stress conditions such as febrile infections, minor head trauma or even acute fright provoke major episodes of neurological deterioration. We present a case of a 2-year-old child who presented with spasticity and cerebellar ataxia. After magnetic resonance imaging (MRI) of the brain, CACH/VWM was diagnosed on the basis of the typical clinical and MRI findings. As there is no known cure for CACH/VWM, our patient was followed up over 3 years with MRIs of the brain to assess the progressive involvement of the cerebral white matter. In those patients with suggestive or inconclusive MRI findings for CACH/VWM, particularly in the presymptomatic stage and adult onset variants, involvement of the inner rim of the corpus callosum should prompt the inclusion of CACH/VWM in the differential diagnosis. Biochemical markers such as the asialotransferrin:transferrin ratio in the cerebrospinal fluid can also potentially be used as a screening tool in this subset of patients prior to gene mutation analysis.

Embryonal rhabdomyosarcoma of the biliary tree in a paediatric patient - A rare cause of obstructive jaundice.

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in the paediatric age group, ranking fourth in frequency after central nervous system tumours, neuroblastomas and nephroblastomas. Embryonal RMS of the biliary tree is considered a rare entity, with the most common clinical presentation being that of obstructive jaundice. We present the case of a 4-year-old boy who presented with hepatomegaly and obstructive jaundice. Biochemically, there was evidence of elevated ductal enzymes with conjugated hyperbilirubinaemia. The magnetic resonance imaging (MRI) features were consistent with a biliary RMS with the differential diagnosis of a choledochal cyst initially included based on the computed tomography images. The diagnosis of embryonal biliary RMS was later confirmed on histology. This case illustrates the importance of considering malignant aetiologies in paediatric cases of obstructive jaundice, as this entity is infrequently described in the literature and may mimic the appearance of a choledochal cyst. The demonstration of enhancement of intraductal material within the biliary tree on MRI and the presence of arterial waveforms within the intraductal mass on ultrasound assists in the differentiation between biliary RMS and a choledochal cyst.

Extra-skeletal Ewing Sarcoma of the chest wall in a child.

Chest wall or pleural-based tumours represent a heterogeneous group of lesions that are infrequent in children and infants; however, a large proportion of these lesions are malignant in nature. Categorising them on the basis of primary versus secondary, site of origin (osseous and cartilage, or soft tissue) and tissue composition may assist in narrowing the differential diagnosis. We present a case of a 7-year-old boy with a progressive history of dyspnoea. The initial chest radiograph (CXR) demonstrated complete opacification of the left hemithorax with no air bronchograms. This was associated with the cut-off of the left main bronchus and mediastinal shift to the right. The post-contrast computed tomography (CT) of the chest showed multiple left-sided enhancing pleural-based masses with collapse of the left lung. These lesions were locally invasive as demonstrated by the intra and extra-thoracic extension. There were no associated erosions of the adjacent ribs or intra-tumoural calcifications. Based on the imaging findings, the diagnosis of extra-skeletal Ewing sarcoma (ES-EWS) of the chest wall was made with a differential diagnosis of rhabdomyosarcoma. A core biopsy was performed of the pleural-based mass, and histology with immunohistochemistry confirmed the diagnosis of a malignant small round blue cell tumour; subtype Ewing sarcoma family tumour (ESFT). The child was subsequently commenced on chemotherapy. The diagnosis of ES-EWS should be considered when a child or adolescent presents with an ill-defined, eccentric, chest wall mass in the absence of a lesion with a primary osseous origin. Imaging plays a key role in tumour staging, therapeutic planning and follow-up of patients.

Pancreatic kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon: A rare entity.

Primary pancreatic tumours are a rare and unusual entity in children. In this article, we present the case of an 8-month-old girl who presented with obstructive jaundice. The differential diagnosis based on imaging studies was that of a pancreatic vascular neoplasm; however, with the laboratory evidence of Kasabach-Merritt phenomenon (KMP), this prompted the diagnosis of pancreatic kaposiform hemangioendothelioma. A core biopsy of the pancreatic mass was taken at laparotomy and confirmed this diagnosis. The pancreas is an exceedingly rare site of occurrence for this tumour, with only nine cases being published to date. The clinical, biochemical, imaging and pathological findings are discussed to highlight a rare and potentially life-threatening vascular tumour.

Effects of Non-Invasive Ventilation Combined with Oxygen Supplementation on Exercise Performance in COPD Patients with Static Lung Hyperinflation and Exercise-Induced Oxygen Desaturation: A Single Blind, Randomized Cross-Over Trial.

The effects of non-invasive ventilation (NIV) in addition to supplemental oxygen on exercise performance in patients with chronic obstructive pulmonary disease (COPD) with hyperinflation and exercise-induced desaturation (EID) remain unclear. We hypothesized that these patients would benefit from NIV and that this effect would be an add-on to oxygen therapy. Thirteen COPD patients with a residual volume >150% of predicted, normal resting arterial oxygen pressure (PaO2) and carbon-dioxide pressure (PaCO2) and EID during a six-minute walk test were included. Patients performed four constant work-rate treadmill tests, each consisting of two exercise bouts with a recovery period in between, wearing an oronasal mask connected to a ventilator and oxygen supply. The ventilator was set to the following settings in fixed order with clockwise rotation: Sham (continuous positive airway pressure (CPAP) 2 cm H2O, FiO2 21%), oxygen (CPAP 2 cm H2O, FiO2 35%), NIV and oxygen (inspiratory positive airway pressure (IPAP) 14 cm H2O/expiratory positive airway pressure (EPAP) 6 cm H2O, inspired oxygen fraction (FiO2) 35%), intermittent (walking: Sham setting, recovery: NIV and oxygen setting). During the first exercise, bout patients walked further with the oxygen setting compared to the sham setting (225 ± 107 vs 120 ± 50 meters, p < 0.05), but even further with the oxygen/NIV setting (283 ± 128 meters; p < 0.05). Recovery time between two exercise bouts was shortest with NIV and oxygen. COPD patients with severe static hyperinflation and EID benefit significantly from NIV in addition to oxygen during exercise and recovery.

Low-density lipoprotein 4: a novel predictor of coronary artery disease severity.

BACKGROUND: Hyperlipidemia is a well established risk factor for coronary artery disease (CAD). Severe CAD has been observed in patients with normal levels of total and low-density lipoprotein (LDL) cholesterol. Small dense LDL particle subtypes (LDL3 and LDL4) have been observed to be more oxidizable and atherogenic. We aimed to identify the role of cholesterol particle subtypes in predicting CAD severity. METHODS: Blood samples were obtained immediately before cardiac catheterization in 179 consecutive patients with suspected CAD. Detailed lipid profiling was performed using a VAP cholesterol test. CAD severity was categorized angiographically as no/minor CAD (<20% luminal diameter stenosis [LDS]), moderate CAD (20% to 74% LDS) and severe CAD (>75% LDS of any major coronary vessel). RESULTS: Patients with severe CAD had significantly higher LDL4 and triglycerides, and lower total HDL, HDL2, HDL3, LDL2 and LDL3 compared to patients with no/minor CAD (p < .05 for all). Multivariate analysis showed high LDL4 as an independent predictive of severe CAD. ROC analysis showed an area under the curve of 0.62 (p < .0001) with a cut-point of >16.9 mg/dL to predict severe CAD with a sensitivity of 53% and specificity of 79%. CONCLUSION: Elevated LDL4 levels are associated with severe CAD. Further large-scale investigations are required to evaluate the utility of LDL4 in predicting CAD severity.

Statin therapy and inflammation in patients with diabetes treated with high dose aspirin.

BACKGROUND: Statin and aspirin form the therapeutic cornerstone in patients with coronary artery disease (CAD) and diabetes. Little is known about relationship of statins with blood thrombogenicity and inflammation in these patients. METHODS: Two hundred nine consecutive patients with diabetes and suspected CAD undergoing elective cardiac catheterization were divided in groups based on statin treatment in the Multi-Analyte, Thrombogenic, and Genetic Markers Atherosclerosis study. Urinary 11-dehydrothromboxane B2 (11-dh-TxB2), lipid profile and oxLDL/ß2GPI were measured by AspirinWorks™ ELISA assay, vertical density gradient ultracentrifugation and immunoassay respectively. Thrombelastography, and ADP- and collagen-induced light transmittance aggregometry assessed thrombogenicity. CAD was classified as none/minor [<20% diameter stenosis (DS)], moderate (20-75% DS), or severe (>75% DS). RESULTS: Severe, moderate, and no CAD was observed in 66, 19, and 15% of patients respectively. Patients on statins had significantly lower 11-dh-TxB2, collagen-induced aggregation, total cholesterol, total LDL, LDL3, oxidized-LDL, Apo B100, and ApoB100/A1 ratio (p<0.01 for all). Statin therapy demonstrated a lower proportion of patients with high urinary 11-dh-TxB2 (>1500pg 11-dh-TxB2/mg creatinine) (25 vs. 57%, p=0.01). CONCLUSION: Statins along with aspirin, confers additional anti-inflammatory and antithrombotic effect in diabetics with CAD. Urinary 11-dh-TxB2 may be a useful biomarker for personalizing statin therapy.

Thrombin-Induced Platelet-Fibrin Clot Strength Identified by Thrombelastography: A Novel Prothrombotic Marker of Coronary Artery Stent Restenosis.

BACKGROUND AND OBJECTIVE: In-stent restenosis (ISR) is a limitation of percutaneous coronary intervention and has been linked to specific clinical and angiographic variables. We aimed to simultaneously assess thrombosis biomarkers and lipid levels in patients with and without ISR. METHODS: Consecutive patients (n = 170) with a history of coronary stenting undergoing elective angiography were studied. Blood samples for thrombelastography, light transmittance aggregometry, and lipid levels were obtained prior to cardiac catheterization. RESULTS: Sixty-nine patients (41%) had ISR (>50% luminal diameter stenosis). Among patients with ISR, 40 (58%) had ISR in more than one stent bed. Patients with ISR were more often female (37.7% vs. 21.8%, P = 0.04), had higher thrombin-induced platelet-fibrin clot strength (TIP-FCS) (69.9 mm vs. 65.6 mm, P < 0.001), and a higher ApoB/A1 ratio (0.65 vs. 0.59, P = 0.03). In patients on dual antiplatelet therapy (n = 86), there were no differences in ADP-, arachidonic acid-, and collagen-induced platelet aggregation between groups. The frequency of patients with ISR increased with TIP-FCS quartiles and by ROC analysis, TIP-FCS = 67.0 mm was the cutpoint for identification of ISR (AUC = 0.80 (95%CI 0.73-0.87, P < 0.0001). By multivariate analysis, TIP-FCS ≥67.0 mm strongly associated with ISR (OR = 7.3, P = 0.004). CONCLUSION: Patients with ISR identified at the time of cardiac catheterization have a prothrombotic phenotype indicated by high TIP-FCS, a novel marker. Studies to confirm the prognostic utility of high TIP-FCS for the development of ISR are ongoing.

Association of weight gain with coronary artery disease, inflammation and thrombogenicity.

Obese individuals, despite having increased cardiovascular (CV) risk factors experience adverse CV outcomes less frequently than non-obese. Little is known about association of long-term weight gain to development of coronary artery disease (CAD), inflammation and thrombogenicity. 418 consecutive patients with suspected CAD undergoing elective cardiac catheterization were included in a sub-analysis of the multi analyte, thrombogenic, and genetic markers of atherosclerosis study. Maximum weight gain (MWG) was defined as percentage increase in weight since age 17 years to year of heaviest weight and categorized as: minor (<30 %), moderate (30-47 %), severe (>47-69 %), and extreme (>69 %). Lipid profiling was determined by vertical density gradient ultracentrifugation, thrombin-induced platelet fibrin clot strength (TIP-FCS) by thrombelastography, and urinary 11-dehydrothromboxane B2 (11-dhTxB2) by ELISA. CAD severity was defined as minimal (<20 %), moderate (20-75 %), and severe (>75 %) luminal diameter obstruction of any major coronary vessel. The mean MWG was 53 ± 33 %. Extreme MWG group had a higher incidence of diabetes mellitus (48 %), hypertension (81 %), depression (25 %), and were most often female (60 %) (p < 0.05 for all). In women, CAD severity was inversely associated to MWG (p = 0.05), whereas in men no such association was observed (p = 0.18). TIP-FCS increased in a stepwise fashion with MWG (p = 0.001). 11-dTxB2 levels were higher in the extreme MWG group, regardless of lipid lowering therapy (p < 0.05). Our data suggest that maximal weight gain since age 17 years is associated with heightened thrombogenicity, inflammation and a poorer lipid profile but not an increased risk for severe CAD development.

Platelet reactivity and thrombogenicity in postmenopausal women.

OBJECTIVE: Age-adjusted incidence of cardiovascular disease, including myocardial infarction, is significantly lower in premenopausal women than in men, which is thought to be caused by the cardioprotective effects of estrogen. However, there is a consistent increase in the incidence of coronary artery disease in postmenopausal women in comparison with premenopausal women. The protective benefit of hormone therapy has not been observed in postmenopausal women. It is unknown whether measures of platelet reactivity and clot strength contribute to the disproportionate incidence of cardiovascular disease between premenopausal and postmenopausal women. METHODS: Fifty healthy volunteers, including 25 premenopausal women and 25 postmenopausal women, aged between 40 and 65 years were enrolled. Total estradiol and follicle-stimulating hormone levels were measured for confirmation of menopausal state and comparison testing. Platelet reactivity was assessed using light transmission aggregometry and P-selectin, and glycoprotein IIb/IIIa receptor expression was assessed using flow cytometry. Thrombelastography was used to measure clot strength, clotting time, and fibrinogen activity. Serum cholesterol, C-reactive protein, complete blood count, and comprehensive metabolic panel were also measured. RESULTS: Platelet reactivity did not differ among menopausal states or hormone levels. Clotting time was increased in postmenopausal women (6.6 ± 2.0 vs. 7.8 ± 1.2 min, P = 0.013) and significantly correlated with estradiol levels (r = 0.68, P < 0.001). A significantly higher low-density lipoprotein cholesterol level was observed in postmenopausal women (P = 0.05). Mean C-reactive protein levels were numerically higher in the postmenopausal group. CONCLUSIONS: The thrombotic risk profile between premenopausal and postmenopausal women is similar. However, improved management of cholesterol may be of clinical benefit. Large-scale studies are required to validate these findings.