Radiation dose management in fluoroscopy procedures: less is more?

The aims of this study are (1) to determine the scattered radiation dose levels in routine fluoroscopy procedures and (2) to compare them with the equivalent chest x-rays and also (3) to monitor common techniques and radiation safety measures taken by the medical officers. The study covered a sample of 105 fluoroscopic procedures performed by 18 medical officers. Each officer wore a personal pocket dosimeter inside the lead gown during each procedure. A digital dosimeter was placed near the detector of the fluoroscopy unit while a survey meter was positioned at the control panel area to record the dose levels. There were 14 types of examination included in this study. The total number of images captured was found to be the highest in barium swallow examination with 115 images, almost five times higher compared to the common practices. The longest screening time was observed in barium enema examination which is 9.15 seconds. The median of the scattered dose level was the highest in barium meal examination (165.50 μSv) which is equivalent to 8.28 times of average dose impart by chest x-ray examinations. The number of images and the length of screening time depend on the competency levels of the medical officers. They capture as many images as possible to avoid missing any abnormalities, therefore it will always be better if the fluoroscopist is consulted during each case. They should also consistently practice essential protection by minimizing exposure time, maximizing distance from the source tube and utilizing the radiation shielding

HIF-mediated suppression of DEPTOR confers resistance to mTOR kinase inhibition in renal cancer

Mechanistic target of rapamycin (mTOR) is a fundamental regulator of cell growth, proliferation, and metabolism. mTOR is activated in renal cancer and accelerates tumor progression. Here, we report that the mTOR inhibitor, DEP domain-containing mTOR-interacting protein (DEPTOR), is strikingly suppressed in clear cell renal cell carcinoma (ccRCC) tumors and cell lines. We demonstrate that DEPTOR is repressed by both hypoxia-inducible factors, HIF-1 and HIF-2, which occurs through activation of the HIF-target gene and transcriptional repressor, BHLHe40/DEC1/Stra13. Restoration of DEPTOR- and CRISPR/Cas9-mediated knockout experiments demonstrate that DEPTOR is growth inhibitory in ccRCC. Furthermore, loss of DEPTOR confers resistance to second-generation mTOR kinase inhibitors through deregulated mTORC1 feedback to IRS-2/PI3K/Akt. This work reveals a hitherto unknown mechanism of resistance to mTOR kinase targeted therapy that is mediated by HIF-dependent reprograming of mTOR/DEPTOR networks and suggests that restoration of DEPTOR in ccRCC will confer sensitivity to mTOR kinase therapeutics

Current and Future Insights for Optimizing Antithrombotic Therapy to Reduce the Burden of Cardiovascular Ischemic Events in Patients with Acute Coronary Syndrome

The pharmacological treatment strategies for acute coronary syndrome (ACS) in recent years are constantly evolving to develop more potent antithrombotic agents, as reflected by the introduction of more novel P2Y12 receptor inhibitors and anticoagulants to reduce the ischemic risk among ACS patients. Despite the substantial improvements in the current antithrombotic regimen, a noticeable number of ACS patients continue to experience ischemic events. Providing effective ischemic risk reduction while balancing bleeding risk remains a clinical challenge. This updated review discusses the currently approved and widely used antithrombotic agents and explores newer antithrombotic treatment strategies under development for the initial phase of ACS

Randomized Placebo-Controlled Double-Blind Clinical Trial of Cannabis-Based Medicinal Product (Sativex) in Painful Diabetic Neuropathy: Depression is a major confounding factor

Objective: To assess the efficacy of Sativex, a cannabis-based medicinal extract, as adjuvant treatment in painful diabetic peripheral neuropathy (DPN). Research design and methods: In this randomized controlled trial, 30 subjects with painful DPN received daily Sativex or placebo. The primary outcome measure was change in mean daily pain scores, and secondary outcome measures included quality-of-life assessments. Results: There was significant improvement in pain scores in both groups, but mean change between groups was not significant. There were no significant differences in secondary outcome measures. Patients with depression had significantly greater baseline pain scores that improved regardless of intervention. Conclusions: This first-ever trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful DPN. Depression was a major confounder and may have important implications for future trials on painful DPN

A preliminary study of brain macrovascular reactivity in impaired glucose tolerance and type-2 diabetes: Quantitative internal carotid artery blood flow using magnetic resonance phase contrast angiography.

OBJECTIVE: The aims of this study were (1) to examine cerebrovascular autoregulation in subjects with impaired glucose tolerance and type 2 diabetes and (2) to clarify whether cardiovascular autonomic nerve function is associated with abnormal cerebrovascular autoregulation. RESEARCH DESIGN AND METHODS: Totally, 46 subjects were recruited (12 = impaired glucose tolerance, 17 = type 2 diabetes and 17 = healthy volunteers). Arterial blood flow was assessed within the internal carotid artery at baseline and 20 min after intravenous pharmacological stress (1 g acetazolamide), using quantitative magnetic resonance phase-contrast angiography. Internal carotid artery vascular reactivity and pulsatility index was determined. All subjects underwent baroreceptor reflex sensitivity assessment. RESULTS: Subjects with impaired glucose tolerance and type 2 diabetes had significantly lower internal carotid artery vascular reactivity [40.2%(19.8) and 41.5%(18.7)], respectively, compared with healthy volunteers [57.0%(14.2); analysis of variance, p = 0.02]. There was no significant difference in internal carotid artery vascular reactivity between type 2 diabetes and impaired glucose tolerance groups (p = 0.84). There was a significant positive correlation between baroreceptor reflex sensitivity (low frequency:high frequency) with cardiac rhythm variability (ρ = 0.47, p = 0.04) and PI (ρ = 0.46, p = 0.04). CONCLUSION: We have demonstrated significant cerebrovascular haemodynamic abnormalities in subjects with type 2 diabetes and impaired glucose tolerance. This was associated with greater sympathovagal imbalance. This may provide an important mechanistic explanation for increased risk of cerebrovascular disease in diabetes. It also highlights that these abnormalities may already be present in prediabetes

Deep learning classification of treatment response in diabetic painful neuropathy: a combined machine learning and magnetic resonance neuroimaging methodological study

Functional magnetic resonance imaging (fMRI) has been shown successfully to assess and stratify patients with painful diabetic peripheral neuropathy (pDPN). This supports the idea of using neuroimaging as a mechanism-based technique to individualise therapy for patients with painful DPN. The aim of this study was to use deep learning to predict treatment response in patients with pDPN using resting state functional imaging (rs-fMRI). We divided 43 painful pDPN patients into responders and non-responders to lidocaine treatment (responders n = 29 and non-responders n = 14). We used rs-fMRI to extract functional connectivity features, using group independent component analysis (gICA), and performed automated treatment response deep learning classification with three-dimensional convolutional neural networks (3D-CNN). Using gICA we achieved an area under the receiver operating characteristic curve (AUC) of 96.60% and F1-Score of 95% in a ten-fold cross validation (CV) experiment using our described 3D-CNN algorithm. To our knowledge, this is the first study utilising deep learning methods to classify treatment response in pDPN

Imbalanced learning: Improving classification of diabetic neuropathy from magnetic resonance imaging

One of the fundamental challenges when dealing with medical imaging datasets is class imbalance. Class imbalance happens where an instance in the class of interest is relatively low, when compared to the rest of the data. This study aims to apply oversampling strategies in an attempt to balance the classes and improve classification performance. We evaluated four different classifiers from k-nearest neighbors (k-NN), support vector machine (SVM), multilayer perceptron (MLP) and decision trees (DT) with 73 oversampling strategies. In this work, we used imbalanced learning oversampling techniques to improve classification in datasets that are distinctively sparser and clustered. This work reports the best oversampling and classifier combinations and concludes that the usage of oversampling methods always outperforms no oversampling strategies hence improving the classification results

High lethality and minimal variation after acute self-poisoning with carbamate insecticides in Sri Lanka – implications for global suicide prevention

Highly hazardous organophosphorus (OP) insecticides are responsible for most pesticide poisoning deaths. As they are removed from agricultural practice, they are often replaced by carbamate insecticides of perceived lower toxicity. However, relatively little is known about poisoning with these insecticides. METHODS: We prospectively studied 1288 patients self-poisoned with carbamate insecticides admitted to six Sri Lankan hospitals. Clinical outcomes were recorded for each patient and plasma carbamate concentration measured in a sample to confirm the carbamate ingested. FINDINGS: Patients had ingested 3% carbofuran powder (719), carbosulfan EC25 liquid (25% w/v, 389), or fenobucarb EC50 liquid (50% w/v, 127) formulations, carbamate insecticides of WHO Toxicity Classes Ib, II, and II, respectively. Intubation and ventilation was required for 183 (14.2%) patients while 71 (5.5%) died. Compared with carbofuran, poisoning with carbosulfan or fenobucarb was associated with significantly higher risk of death [carbofuran 2.2%; carbosulfan 11.1%, OR 5.5 (95% CI 3.0-9.8); fenobucarb 6.3%, OR 3.0 (1.2-7.1)] and intubation [carbofuran 6.1%; carbosulfan 27.0%, OR 5.7 (3.9-8.3); fenobucarb 18.9%, OR 3.6 (2.1-6.1)]. The clinical presentation and cause of death did not differ markedly between carbamates. Median time to death was similar: carbofuran 42.3 h (IQR 5.5-67.3), carbosulfan 21.3 h (11.5-71.3), and fenobucarb 25.3 h (17.3-72.1) (p = 0.99); no patients showed delayed onset of toxicity akin to the intermediate syndrome seen after OP insecticide poisoning. For survivors, median duration of intubation was 67.8 h (IQR 27.5-118.8) with no difference in duration between carbamates. Reduced GCS at presentation was associated with worse outcome although some patients with carbosulfan died after presentation with normal GCS. CONCLUSIONS: We did not find carbamate insecticide self-poisoning to vary markedly according to the carbamate ingested although the case fatality varied according to the concentration and formulation of the insecticide. Carbamate poisoning did not appear to be much less toxic than poisoning with some liquid OP insecticide formulations, e.g., chlorpyrifos EC40, that we have previously noted in these same hospitals (Lancet 2005, 366:1452-1459; QJM 2006, 99:513-522). Replacement of WHO Class II Toxicity OP insecticides in agriculture with high-strength liquid carbamate formulations may not substantially reduce case fatality after pesticide poisoning and, therefore, global suicide rates.NHMRC Grant 07166

High lethality and minimal variation after acute self-poisoning with carbamate insecticides in Sri Lanka - implications for global suicide prevention

Highly hazardous organophosphorus (OP) insecticides are responsible for most pesticide poisoning deaths. As they are removed from agricultural practice, they are often replaced by carbamate insecticides of perceived lower toxicity. However, relatively little is known about poisoning with these insecticides. METHODS: We prospectively studied 1288 patients self-poisoned with carbamate insecticides admitted to six Sri Lankan hospitals. Clinical outcomes were recorded for each patient and plasma carbamate concentration measured in a sample to confirm the carbamate ingested. FINDINGS: Patients had ingested 3% carbofuran powder (719), carbosulfan EC25 liquid (25% w/v, 389), or fenobucarb EC50 liquid (50% w/v, 127) formulations, carbamate insecticides of WHO Toxicity Classes Ib, II, and II, respectively. Intubation and ventilation was required for 183 (14.2%) patients while 71 (5.5%) died. Compared with carbofuran, poisoning with carbosulfan or fenobucarb was associated with significantly higher risk of death [carbofuran 2.2%; carbosulfan 11.1%, OR 5.5 (95% CI 3.0-9.8); fenobucarb 6.3%, OR 3.0 (1.2-7.1)] and intubation [carbofuran 6.1%; carbosulfan 27.0%, OR 5.7 (3.9-8.3); fenobucarb 18.9%, OR 3.6 (2.1-6.1)]. The clinical presentation and cause of death did not differ markedly between carbamates. Median time to death was similar: carbofuran 42.3 h (IQR 5.5-67.3), carbosulfan 21.3 h (11.5-71.3), and fenobucarb 25.3 h (17.3-72.1) (p = 0.99); no patients showed delayed onset of toxicity akin to the intermediate syndrome seen after OP insecticide poisoning. For survivors, median duration of intubation was 67.8 h (IQR 27.5-118.8) with no difference in duration between carbamates. Reduced GCS at presentation was associated with worse outcome although some patients with carbosulfan died after presentation with normal GCS. CONCLUSIONS: We did not find carbamate insecticide self-poisoning to vary markedly according to the carbamate ingested although the case fatality varied according to the concentration and formulation of the insecticide. Carbamate poisoning did not appear to be much less toxic than poisoning with some liquid OP insecticide formulations, e.g., chlorpyrifos EC40, that we have previously noted in these same hospitals (Lancet 2005, 366:1452-1459; QJM 2006, 99:513-522). Replacement of WHO Class II Toxicity OP insecticides in agriculture with high-strength liquid carbamate formulations may not substantially reduce case fatality after pesticide poisoning and, therefore, global suicide rates.NHMRC Grant 07166