Effects of photobiomodulation and caffeine treatment on acute kidney injury in a hypoxic ischemic neonatal rat model.

Hypoxic ischemic encephalopathy (HIE) occurs in 2-5/1000 births, with acute kidney injury (AKI) occurring in 40%. AKI increases morbidity and mortality. Caffeine, an adenosine receptor antagonist, and photobiomodulation (PBM), working on cytochrome c oxidase, are potential treatments for AKI. To examine effects of caffeine and PBM on AKI in rats, Day 7 pups underwent a HIE intervention (Modified Rice-Vannucci model) replicating pathology observed in humans. Caffeine was administered for 3 days and/or PBM for 5 days following HIE. Weights and urine for biomarkers (NGAL, albumin, KIM-1, osteopontin) were collected prior to HIE, daily post intervention and at sacrifice. Both treatments reduced kidney injury seen on electron microscopy, but not when combined. HIE elevated urinary NGAL and albumin on Days 1-3 post-HIE, before returning to control levels. This elevation was significantly reduced by PBM or caffeine. KIM-1 was significantly elevated for 7 days post-HIE and was reduced by both treatments. Osteopontin was not altered by HIE or the treatments. Treatments, individually but not in combination, improved HIE-induced reductions in the enzymatic activity of mitochondrial complexes II-III. PBM and caffeine also improved weight gain. PBM and caffeine reduces AKI diagnosed by urinary biomarkers and confirmed by EM findings.

CT-based texture analysis potentially provides prognostic information complementary to interim fdg-pet for patients with hodgkin's and aggressive non-hodgkin's lymphomas.

OBJECTIVES: The purpose of this study was to investigate the ability of computed tomography texture analysis (CTTA) to provide additional prognostic information in patients with Hodgkin's lymphoma (HL) and high-grade non-Hodgkin's lymphoma (NHL). METHODS: This retrospective, pilot-study approved by the IRB comprised 45 lymphoma patients undergoing routine 18F-FDG-PET-CT. Progression-free survival (PFS) was determined from clinical follow-up (mean-duration: 40 months; range: 10-62 months). Non-contrast-enhanced low-dose CT images were submitted to CTTA comprising image filtration to highlight features of different sizes followed by histogram-analysis using kurtosis. Prognostic value of CTTA was compared to PET FDG-uptake value, tumour-stage, tumour-bulk, lymphoma-type, treatment-regime, and interim FDG-PET (iPET) status using Kaplan-Meier analysis. Cox regression analysis determined the independence of significantly prognostic imaging and clinical features. RESULTS: A total of 27 patients had aggressive NHL and 18 had HL. Mean PFS was 48.5 months. There was no significant difference in pre-treatment CTTA between the lymphoma sub-types. Kaplan-Meier analysis found pre-treatment CTTA (medium feature scale, p=0.010) and iPET status (p<0.001) to be significant predictors of PFS. Cox analysis revealed that an interaction between pre-treatment CTTA and iPET status was the only independent predictor of PFS (HR: 25.5, 95% CI: 5.4-120, p<0.001). Specifically, pre-treatment CTTA risk stratified patients with negative iPET. CONCLUSION: CTTA can potentially provide prognostic information complementary to iPET for patients with HL and aggressive NHL. KEY POINTS: • CT texture-analysis (CTTA) provides prognostic information complementary to interim FDG-PET in Lymphoma. • Pre-treatment CTTA and interim PET status were significant predictors of progression-free survival. • Patients with negative interim PET could be further stratified by pre-treatment CTTA. • Provide precision surveillance where additional imaging reserved for patients at greatest recurrence-risk. • Assists in risk-adapted treatment strategy based on interim PET and CTTA.

Accuracy and cost-effectiveness of dynamic contrast-enhanced CT in the characterisation of solitary pulmonary nodules-the SPUtNIk study.

INTRODUCTION: Solitary pulmonary nodules (SPNs) are common on CT. The most cost-effective investigation algorithm is still to be determined. Dynamic contrast-enhanced CT (DCE-CT) is an established diagnostic test not widely available in the UK currently. METHODS AND ANALYSIS: The SPUtNIk study will assess the diagnostic accuracy, clinical utility and cost-effectiveness of DCE-CT, alongside the current CT and 18-flurodeoxyglucose-positron emission tomography) (18FDG-PET)-CT nodule characterisation strategies in the National Health Service (NHS). Image acquisition and data analysis for 18FDG-PET-CT and DCE-CT will follow a standardised protocol with central review of 10% to ensure quality assurance. Decision analytic modelling will assess the likely costs and health outcomes resulting from incorporation of DCE-CT into management strategies for patients with SPNs. ETHICS AND DISSEMINATION: Approval has been granted by the South West Research Ethics Committee. Ethics reference number 12/SW/0206. The results of the trial will be presented at national and international meetings and published in an Health Technology Assessment (HTA) Monograph and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN30784948; Pre-results.

Current status and guidelines for the assessment of tumour vascular support with dynamic contrast-enhanced computed tomography.

Dynamic contrast-enhanced computed tomography (DCE-CT) assesses the vascular support of tumours through analysis of temporal changes in attenuation in blood vessels and tissues during a rapid series of images acquired with intravenous administration of iodinated contrast material. Commercial software for DCE-CT analysis allows pixel-by-pixel calculation of a range of validated physiological parameters and depiction as parametric maps. Clinical studies support the use of DCE-CT parameters as surrogates for physiological and molecular processes underlying tumour angiogenesis. DCE-CT has been used to provide biomarkers of drug action in early phase trials for the treatment of a range of cancers. DCE-CT can be appended to current imaging assessments of tumour response with the benefits of wide availability and low cost. This paper sets out guidelines for the use of DCE-CT in assessing tumour vascular support that were developed using a Delphi process. Recommendations encompass CT system requirements and quality assurance, radiation dosimetry, patient preparation, administration of contrast material, CT acquisition parameters, terminology and units, data processing and reporting. DCE-CT has reached technical maturity for use in therapeutic trials in oncology. The development of these consensus guidelines may promote broader application of DCE-CT for the evaluation of tumour vascularity. Key Points • DCE-CT can robustly assess tumour vascular support • DCE-CT has reached technical maturity for use in therapeutic trials in oncology • This paper presents consensus guidelines for using DCE-CT in assessing tumour vascularity.

Increased metabolic activity in abdominal aortic aneurysm detected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT).

OBJECTIVES: Abdominal aortic aneurysms (AAAs) are associated with an inflammatory cell infiltrate and enzymatic degradation of the vessel wall. The aim of this study was to detect increased metabolic activity in the wall of the AAA with 18F-fluorodeoxyglucose ((18)F-FDG), mediated by glucose transporter protein (GLUTs), using a dedicated hybrid PET/64-detector CT. DESIGN, METHOD AND MATERIALS: 14 patients (All male, mean age 73.6 years, range 61-82) with AAA under surveillance underwent PET/CT scanning with 175 MBq of intravenous (18)F-FDG. The maximum aneurysm diameter and calcification score were determined on the attenuation correction CT. A volume of interest was placed on the aneurysm sac and the maximum Standardised Uptake Value (SUV(max)) measured. RESULTS: The mean aneurysm diameter was 5.4 cm (SD+/-0.8). Two aneurysms had the CT characteristics of inflammatory aneurysms. Twelve aneurysms showed increased FDG uptake (SUV(max)>2.5). There was no significant difference in FDG uptake between heavily calcified aneurysms and non-heavily calcified aneurysms (t-test). There was a significant increase in the FDG uptake in the two inflammatory aneurysms compared to the other twelve aneurysms (t-test; P=0.04). CONCLUSION: The findings in this study offer in vivo evidence that the AAA wall shows increased glucose metabolism, mediated by the GLUTs: this increased metabolic activity as detected by PET/CT may be present in most AAAs.

Comparison of shuttle walk with measured peak oxygen consumption in patients with operable lung cancer.

BACKGROUND: The relationship between the shuttle walk test and peak oxygen consumption in patients with lung cancer has not previously been reported. A study was undertaken to examine this relationship in patients referred for lung cancer surgery to test the hypothesis that the shuttle walk test would be useful in this clinical setting. METHODS: 125 consecutive patients with potentially operable lung cancer were prospectively recruited. Each performed same day shuttle walking and treadmill walking tests. RESULTS: Shuttle walk distances ranged from 104 m to 1020 m and peak oxygen consumption ranged from 9 to 35 ml/kg/min. The shuttle walk distance significantly correlated with peak oxygen consumption (r = 0.67, p<0.001). All 55 patients who achieved more than 400 m on the shuttle test had a peak oxygen consumption of at least 15 ml/kg/min. Seventy of 125 patients failed to achieve 400 m on the shuttle walk test; in 22 of these the peak oxygen consumption was less than 15 ml/kg/min. Nine of 17 patients who achieved less than 250 m had a peak oxygen consumption of more than 15 ml/kg/min. CONCLUSION: The shuttle walk is a useful exercise test to assess potentially operable lung cancer patients with borderline lung function. However, it tends to underestimate exercise capacity at the lower range compared with peak oxygen consumption. Our data suggest that patients achieving 400 m on the shuttle walk test do not require formal measurement of oxygen consumption. In patients failing to achieve this distance we recommend assessment of peak oxygen consumption, particularly in those unable to walk 250 m, because a considerable proportion would still qualify for surgery as they had an acceptable peak oxygen consumption.

Relationship between pulmonary function and lung cancer surgical outcome.

The British Thoracic Society and American College of Chest Physician guidelines outline criteria for investigating patients for lung cancer surgery. However, the guidelines are based on relatively old studies. Therefore, the relationship between pulmonary function test results and surgical outcome were studied prospectively in a large cohort of lung cancer patients. From January 2001 to December 2003, 110 patients underwent surgery for lung cancer. All underwent full lung function testing in order to predict post-operative lung function. The hospital mortality rate was 3% and major complication rate 22%. There was poor overall outcome in 13%. Mean pre-operative lung function values were: forced expiratory volume in one second (FEV1) 2.0 L (79.4% of the predicted value), and carbon monoxide diffusing capacity of the lung (D(L,CO)) 73.6% pred. The mean post-operative lung function values were: FEV1 1.4 L (55.6% pred), and D(L,CO) 51.3% pred. All lung function values were better predictors of poor surgical outcome when expressed as a percentage of the predicted value. Using a threshold of pre-operative FEV1 of 47% pred resulted in the most useful positive and negative predictive probabilities, 0.90 and 0.67, respectively. Lung function values expressed as a percentage of the predicted value are more useful predictors of post-operative outcome than absolute values. The threshold of predicted forced expiratory volume in one second for surgical intervention could be lower (45-50% pred) than is currently accepted without increased mortality.

The value of performing head CT in screening for cerebral metastases in patients with potentially resectable non-small cell lung cancer: experience from a UK cardiothoracic centre.

AIM: To evaluate the whether screening for cerebral metastases in neurologically intact patients with potentially resectable non-small cell lung cancer patients is both worthwhile and cost-effective. METHODS: We prospectively performed computed tomography (CT) of the head in 105 consecutive patients with potentially resectable lung cancer over an 18-month period. None of these patients had neurological symptoms or signs. RESULTS: Five patients (4.8%) with cerebral metastases were identified using CT. At our institution the financial saving of avoiding five thoracotomies was pound sterling 45,000, whilst the cost of performing 105 head CTs was pound sterling 16,000. This represented a substantial saving for the healthcare provider and preserved the quality of life in five patients. CONCLUSIONS: We conclude that screening for cerebral metastases in neurologically intact patients with potentially resectable non small cell lung cancer patients is both worthwhile and cost effective.

Neonatal alloimmune thrombocytopenia may be less severe in a subsequent pregnancy.

Neonatal alloimmune thrombocytopenia (NAIT) is more common than previously appreciated. Clinical presentation is varied, but it is generally a severe disorder and it is said to be more severe in subsequent pregnancies. The authors present a case of fatal disseminated intravascular coagulation that was diagnosed as NAIT only after presentation of a subsequent surviving sibling with intracranial hemorrhage and thrombocytopenia. Despite the perinatal complications, this second sibling had good neurodevelopmental outcome. This is the first reported case of less severe disease occurring in a subsequent pregnancy.

Cardiac tumours in intrauterine life.

Since 1980, 11 examples of cardiac tumour have been detected in the fetus out of a total of 794 congenital cardiac malformations. Patients were referred because of fetal hydrops in two, a family history of tuberous sclerosis in two, and because of the detection of a tumour mass during a scan at the local hospital in seven. The gestational age range at presentation was from 20-34 weeks. Of eight fetuses where death occurred, the histological type was rhabdomyoma in seven and teratoma in one. In seven cases, the lesion appeared single and in four there were multiple tumours. In two of the cases of rhabdomyoma, other family members had evidence of tuberous sclerosis. Termination of pregnancy took place in four cases; of seven continuing pregnancies, spontaneous intrauterine death occurred in four, and three children are still alive. Two of the three survivors has the clinical picture of tuberous sclerosis. The last case is as yet only 1 month old. In summary, even where the lesion is single, the most likely diagnosis in fetal cardiac tumour is rhabdomyoma, with associated tuberous sclerosis. However, the characteristic features of this latter condition may not become evident until some months after birth.