Association of residential greenness with the risk of metabolic syndrome in Chinese older adults: a longitudinal cohort study.

AIMS: We aimed to investigate the association between residential greenness and MetS in older Chinese adults. METHODS: Longitudinal data on sociodemographic characteristics and lifestyle were collected from the Shenzhen Healthy Ageing Research (SHARE) cohort. Greenness exposure was assessed through satellite-derived Normalized Difference Vegetation Index (NDVI) values in the 250-m, 500-m, and 1250-m radius around the residential address for each participant. MetS was defined by standard guidelines for the Chinese population. RESULTS: A total of 49,893 older Chinese adults with a mean age of 70.96 (SD = 5.26) years were included in the study. In the fully adjusted models, participants who lived in the highest quartile of NDVI250-m, NDVI500-m, and NDVI1250-m had a 15% (odds ratio, OR = 0.85, 95% confidence interval, CI: 0.80-0.90), 12% (OR = 0.88, 95% CI: 0.83-0.93), and 11% (OR = 0.89, 95% CI: 0.85-0.95) lower incidence of MetS, respectively, than those living in the lowest quartile (all p-trend < 0.01). Interactions and subgroup analyses showed that age, sex, smoking status, and drinking status were significant effect modifiers (p-interaction for all NDVI < 0.05). CONCLUSIONS: Residential greenness is associated with a lower risk of MetS in Chinese older adults, especially for young older adults, females, non-smokers, and non-drinkers.

The CT Swirl Sign Is Associated with Hematoma Expansion in Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Hematoma expansion is an independent determinant of poor clinical outcome in intracerebral hemorrhage. Although the "spot sign" predicts hematoma expansion, the identification requires CT angiography, which limits its general accessibility in some hospital settings. Noncontrast CT, without the need for CT angiography, may identify sites of active extravasation, termed the "swirl sign." We aimed to determine the association of the swirl sign with hematoma expansion. MATERIALS AND METHODS: Patients with spontaneous intracerebral hemorrhage between 2007 and 2014 who underwent an initial and subsequent noncontrast CT at a single center were retrospectively identified. The swirl sign, on noncontrast CT, was defined as iso- or hypodensity within a hyperdense region that extended across 2 contiguous 5-mm axial CT sections. RESULTS: A total of 212 patients met the inclusion criteria. The swirl sign was identified in 91 patients with excellent interobserver agreement (κ = 0.87). The swirl sign was associated with larger initial hematoma (P < .001) and earlier initial CT (P < .001) and hematoma expansion (P = .028). Multivariable regression modeling demonstrated that if one assumed similar initial hematoma volume, onset-to-first scan, and time between CT scans, the median absolute hematoma growth was 5.77 mL (95% CI, 2.37-9.18 mL; P = .001) and relative growth was 35.6% (95% CI, 18.5%-52.6%; P < .001) higher in patients with the swirl sign compared with those without. CONCLUSIONS: The NCCT swirl sign was reliably identified and is associated with hematoma expansion. We propose that the swirl sign be included in risk stratification of intracerebral hemorrhage and considered for inclusion in clinical trials.

Association between CYP2C19 Polymorphisms and Outcomes in Cerebral Endovascular Therapy.

BACKGROUND AND PURPOSE: Differing responses to clopidogrel following endovascular treatment of cerebrovascular diseases may increase the risk of vascular complications. CYP2C19 gene polymorphisms influence clopidogrel activity. We aimed to study the clinical impact of CYP2C19 gene polymorphisms in patients undergoing endovascular treatment. MATERIALS AND METHODS: This was a prospective, longitudinal, observational study. Information on demographics and cerebrovascular status was collected as baseline. Clopidogrel response was tested by the VerifyNow P2Y12 assay. CYP2C19 genotyping was undertaken by polymerase chain reaction-restriction fragment length polymorphism. Three-month follow-up data included vascular complications, mortality, and modified Rankin Scale score. Associations were investigated among CYP2C19 genotypes, clopidogrel responsiveness, and clinical outcomes. RESULTS: One hundred and eight participants were included. Median age was 56 years (interquartile range, 48.8-65.0 years), and 35 (32.4%) were male. Forty-four participants were classified into group 1 (homozygous CYP2C19*1/*1); 31, into group 2 (25 with CYP2C19*1/*2, two with CYP2C19*1/*3, three with CYP2C19*3/*3, one with CYP2C19*2/*3); 28, into group 3 (24 with CYP2C19*1/*17, four with CYP2C19*17/*17); and 5, into group 4 (CYP2C19*2/*17). A significantly higher proportion of participants in group 3 experienced ischemic events (9 of 28, 32.1%) compared with group 1 (5 of 44, 11.4%; P = .04; odds ratio, 3.7; 95% confidence interval, 1.1-12.6). There was no significant difference in clopidogrel response among the 4 genotype groups. CONCLUSIONS: Individuals with CYP2C19*17 may have increased risk of ischemic events following endovascular treatment, independent of clopidogrel responsiveness. Larger studies are required to confirm the influence of CYP2C19*17 on clinical outcomes and to understand the mechanisms for increased ischemic events.

Advances in endovascular treatment of acute ischaemic stroke.

Over the past decade, there have been rapid advancements in ischaemic stroke reperfusion treatments. However, clear clinical benefit is yet to be shown in large clinical trials. In this review, the major studies in different types of endovascular treatments including intra-arterial thrombolysis, aspiration devices, mechanical clot retrievers and the new stent retrievers are discussed. First-generation mechanical thrombectomy devices such as the MERCI Retriever (Stryker, Kalamazoo, MI, USA) and Penumbra aspiration device (Penumbra Inc., Alameda, CA, USA) demonstrated safety and higher rates of recanalisation in the MERCI and Penumbra Pivotal Stroke Trial; however, there was no significant improvement in clinical outcome. Second-generation endovascular stent retrieval devices Solitaire (ev3 Neurovascular, Irvine, CA, USA) and Trevo (Stryker) have shown promising results. In preliminary trials, SOLITAIRE with the Intention for Thrombectomy (SWIFT) and Thrombectomy Revascularization of Large Vessel Occlusions (TREVO), both showed rates of recanalisation close to 90% and significantly improved clinical outcomes compared with the MERCI study, but the recent landmark studies for endovascular treatment (Interventional Management of Stroke (IMS III), Mechanical Retrieval and Recanalisation of Stroke Clots Using Embolectomy (MR-RESCUE) and SYNTHESIS) did not show any clinical benefit from endovascular treatment compared with standard intravenous therapy. However, moving forward, the recent Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands (MR-CLEAN) study results have shown marked improvements in recanalisation, reperfusion and functional outcome in patients receiving endovascular treatment (97% using stent retrievers) within 6 h in addition to standard medical care. Overall, although evidence regarding the efficacy of endovascular treatment in acute stroke has been equivocal, recent publications of large multicentre randomised controlled trials indicate benefit of intra-arterial stent retriever reperfusion in patients selected by appropriate imaging and treated early by experienced operators, and it will likely remain an important adjunct to established medical treatment with intravenous tPA.

Picture-to-puncture time in acute stroke endovascular intervention: are we getting faster?

BACKGROUND: In acute stroke management, time efficiency in the continuum of patient management is critical. We aimed to determine if implementation of system improvements at our institution translated to reduced picture-to-puncture (P2P) times over a 6-year period. METHODS: We conducted a single-center retrospective analysis using a prospective acute stroke database of patients treated with intra-arterial therapy from October 2007 to October 2013. Patient demographics, stroke severity, neuroimaging and treatment time points were collected. Annual P2P times, defined as the interval between pretreatment neuroimaging (picture) and commencement of intra-arterial therapy (puncture), were assessed and compared. RESULTS: From 2007 to 2013 a total of 189 patients were identified, of which 181 met the study criteria. At initial presentation, median baseline NIH Stroke Severity score was 17.00 (IQR 11.00-22.00). Annual median P2P times decreased from 171 to 123.5 min, showing a median decrease of 11.5 min per annum (95% CI -23.9 to 0.9) and trending towards statistical significance (p=0.069). Plotted data revealed longer P2P times in instances where stroke onset or CT acquisition times were out-of-hours. Using median regression modeling, the annual decrease in P2P median time reached statistical significance when independently adjusting for CT acquisition time (13.5 min P2P median time reduction, 95% CI -27.0 to -0.1, p=0.048) and for stroke onset time (14.5 min annual P2P median time reduction, 95% CI -26.1 to -2.8, p=0.015). CONCLUSIONS: As a consequence of systems improvement at our institution, we were able to demonstrate improved annual median P2P times from 2007 to 2013.

The impact of arterial collateralization on outcome after intra-arterial therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: Although intra-arterial therapy for acute ischemic stroke is associated with superior recanalization rates, improved clinical outcomes are inconsistently observed following successful recanalization. There is emerging concern that unfavorable arterial collateralization, though unproven, predetermines poor outcome. We hypothesized that poor leptomeningeal collateralization, assessed by preprocedural CTA, is associated with poor outcome in patients with acute ischemic stroke undergoing intra-arterial therapy. MATERIALS AND METHODS: We retrospectively analyzed patients with acute ischemic stroke with intracranial ICA and/or MCA occlusions who received intra-arterial therapy. The collaterals were graded on CTA. Univariate and multivariate analyses were used to investigate the association between the dichotomized leptomeningeal collateral score and functional outcomes at 3-months mRS ≤2, mortality, and intracranial hemorrhages. RESULTS: Eighty-seven patients were included. The median age was 66 years (interquartile range, 54-76 years) and the median NIHSS score at admission was 18 (interquartile range, 14-20). The leptomeningeal collateral score 3 was found to have significant association with the good functional outcome at 3 months: OR = 3.13; 95% CI, 1.25-7.825; P = .016. This association remained significant when adjusted for the use of IV tissue plasminogen activator: alone, OR = 2.998; 95% CI, 1.154-7.786; P = .024; and for IV tissue plasminogen activator and other confounders (age, baseline NIHSS score, and Thrombolysis in Cerebral Infarction grades), OR = 2.985; 95% CI, 1.027-8.673; P = .045. CONCLUSIONS: We found that poor arterial collateralization, defined as a collateral score of <3, was associated with poor outcome, after adjustment for recanalization success. We recommend that future studies include collateral scores as one of the predictors of functional outcome.

Advances in medical revascularisation treatments in acute ischemic stroke.

Urgent reperfusion of the ischaemic brain is the aim of stroke treatment and there has been ongoing research to find a drug that can promote vessel recanalisation more completely and with less side effects. In this review article, the major studies which have validated the use and safety of tPA are discussed. The safety and efficacy of other thrombolytic and anticoagulative agents such as tenecteplase, desmoteplase, ancrod, tirofiban, abciximab, eptifibatide, and argatroban are also reviewed. Tenecteplase and desmoteplase are both plasminogen activators with higher fibrin affinity and longer half-life compared to alteplase. They have shown greater reperfusion rates and improved functional outcomes in preliminary studies. Argatroban is a direct thrombin inhibitor used as an adjunct to intravenous tPA and showed higher rates of complete recanalisation in the ARTTS study with further studies which are now ongoing. Adjuvant thrombolysis techniques using transcranial ultrasound are also being investigated and have shown higher rates of complete recanalisation, for example, in the CLOTBUST study. Overall, development in medical therapies for stroke is important due to the ease of administration compared to endovascular treatments, and the new treatments such as tenecteplase, desmoteplase, and adjuvant sonothrombolysis are showing promising results and await further large-scale clinical trials.

Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress.

Loss of function of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor gene is associated with many human cancers. In the cytoplasm, PTEN antagonizes the phosphatidylinositol 3-kinase (PI3K) signaling pathway. PTEN also accumulates in the nucleus, where its function remains poorly understood. We demonstrate that SUMOylation (SUMO, small ubiquitin-like modifier) of PTEN controls its nuclear localization. In cells exposed to genotoxic stress, SUMO-PTEN was rapidly excluded from the nucleus dependent on the protein kinase ataxia telangiectasia mutated (ATM). Cells lacking nuclear PTEN were hypersensitive to DNA damage, whereas PTEN-deficient cells were susceptible to killing by a combination of genotoxic stress and a small-molecule PI3K inhibitor both in vitro and in vivo. Our findings may have implications for individualized therapy for patients with PTEN-deficient tumors.

The use of a bone-anchored device as a hard-wired conduit for transmitting EMG signals from implanted muscle electrodes.

The use of a bone-anchored device to transmit electrical signals from internalized muscle electrodes was studied in a sheep model. The bone-anchored device was used as a conduit for the passage of a wire connecting an internal epimysial electrode to an external signal-recording device. The bone-anchored device was inserted into an intact tibia and the electrode attached to the adjacent M. peroneus tertius. "Physiological" signals with low signal-to-noise ratios were successfully obtained over a 12-week period by walking the sheep on a treadmill. Reliable transmission of multiple muscle signals across the skin barrier is essential for providing intuitive, biomimetic upper limb prostheses. This technology has the potential to provide a better functional and reliable solution for upper limb amputee rehabilitation: attachment and control.

Clopidogrel hyper-response and bleeding risk in neurointerventional procedures.

BACKGROUND AND PURPOSE: Antiplatelet therapy is associated with decreased ischemic events after neurointerventional procedures. Antiplatelet resistance negates the protective effects of antiplatelet medication, leading to a higher incidence of ischemic events. A possible link between antiplatelet hyper-response and increased hemorrhagic complications has been inadequately investigated. We aimed to examine the correlation between antiplatelet hyper-response and the risk of hemorrhagic complications. MATERIALS AND METHODS: Patients who were treated with antiplatelet medications and underwent neurointerventional procedures were prospectively recruited. We collected the following data: demographics, vascular risk factors, antiplatelet and anticoagulation treatment, antiplatelet responsiveness, coagulation profile, and hemorrhagic complications. P2Y12 receptor-mediated platelet inhibition was tested by using the VerifyNow assay device. The primary end points were postprocedural major and minor hemorrhagic complications. Receiver operator characteristic analysis was used to evaluate the percentage of platelet inhibition as a diagnostic tool for bleeding events. The association between hemorrhage and percentage of platelet inhibition was investigated by using logistic regression modeling. RESULTS: Forty-seven patients were enrolled. The mean age was 56±12 years, and 28% were men. Ten patients (21.3%) developed hemorrhagic complications. Clopidogrel response was higher in patients with a major bleeding complication compared with those with minor or no bleeding (median, 94% versus 24% platelet inhibition; P=.0084). Of the 7 patients (14.9%) defined as hyper-responders with ≥72% platelet inhibition, 42.8% had a major bleeding complication. CONCLUSIONS: Hyper-response to clopidogrel is associated with increased risk of hemorrhagic complications. Larger studies are urgently needed to validate a clinically useful threshold to define clopidogrel hyper-response and to examine the clinical effects of antiplatelet dosage adjustment.

Is general anaesthesia preferable to conscious sedation in the treatment of acute ischaemic stroke with intra-arterial mechanical thrombectomy? A review of the literature.

INTRODUCTION: Intra-arterial mechanical thrombectomy (IAMT) is an endovascular technique that allows for the acute retrieval of intravascular thrombi and is increasingly being used for the treatment of acute ischaemic stroke (AIS). There are currently two anaesthetic options during IAMT: general anaesthesia (GA) and conscious sedation (CS). The decision to use GA versus CS is the source of controversy, as it requires careful balance between patient pain, movement and airway protection whilst minimising time delay and haemodynamic fluctuations. This review examines and summarises the evidence for the use of GA versus CS in the treatment of AIS by IAMT. METHODS: Studies were identified using systematic bibliographic searches. The five applicable studies were analysed with reference to overall outcomes and the key parameters that govern the decision to use GA or CS. The key parameters included the impact of GA and CS on pain, complication rates, time delays, airway protection and haemodynamic stability. RESULTS: Several retrospective analyses have shown that the use of GA is associated with adverse outcomes. CONCLUSION: Intra-arterial mechanical thrombectomy under general anaesthesia is associated with poor outcomes in observational studies. It is reasonable to offer conscious sedation as the preferred option where adverse patient factors such as agitation are lacking.

A single centre study of coil embolization of intracranial aneurysms comparing bare platinum and PGLA-coated coils.

There is no robust consensus on the efficacy of polyglycolic/polylactic acid (PGLA)-coated coils used in the endovascular embolization of intracranial aneurysms. We present a comparative study of bare platinum coils and PGLA-coated Gugliemi Detachable Coils (GDC) in the treatment of intracranial aneurysms at a single centre, using target aneurysm recurrence and angiographic recanalization as the primary endpoints. We included all patients treated between 1998 and 2009 who had undergone at least one angiographic post-procedural follow-up. Patient demographics, clinical presentation, operative notes, and all relevant imaging were collected. Of the 441 aneurysms with follow-up, 290 were treated with at least one PGLA coil and 151 aneurysms were treated exclusively with bare platinum coils. At follow-up, 26.5% of platinum controls demonstrated angiographic recanalization, compared to 31.4% of PGLA-treated aneurysms (p=0.002). PGLA-treated aneurysms were more likely to have an angiographic remnant at follow-up (odds ratio [OR]=1.96, 95% confidence interval [CI]=1.26-3.04, p=0.003). The post-operative Raymond score was the only predictor of retreatment (OR=1.6, 95% CI=1.08-2.24, p=0.020), and was the second strongest predictor of a complete angiographic result at follow-up (OR=1.67, 95% CI=1.22-2.27, p=0.001). We concluded that PGLA-coated coils demonstrated poorer post-operative and long-term angiographic occlusion in the treatment of intracranial aneurysms, compared to bare platinum coils.

Flow dynamics of a novel counterpulsation device characterized by CFD and PIV modeling.

BACKGROUND: Historically, single port valveless pneumatic blood pumps have had a high incidence of thrombus formation due to areas of blood stagnation and hemolysis due to areas of high shear stress. METHODS: To ensure minimal hemolysis and favorable blood washing characteristics, particle image velocimetry (PIV) and computational fluid dynamics (CFD) were used to evaluate the design of a new single port, valveless counterpulsation device (Symphony). The Symphony design was tested in 6-h acute (n=8), 5-day (n=8) and 30-day (n=2) chronic experiments in a calf model (Jersey, 76 kg). Venous blood samples were collected during acute (hourly) and chronic (weekly) time courses to analyze for temporal changes in biochemical markers and quantify plasma free hemoglobin. At the end of the study, animals were euthanized and the Symphony and end-organs (brain, liver, kidney, lungs, heart, and spleen) were examined for thrombus formations. RESULTS: Both the PIV and the CFD showed the development of a strong moving vortex during filling phase and that blood exited the Symphony uniformly from all areas during ejection phase. The laminar shear stresses estimated by CFD remained well below the hemolysis threshold of 400 Pa inside the Symphony throughout filling and ejection phases. No areas of persistent blood stagnation or flow separation were observed. The maximum plasma free hemoglobin (<10mg/dl), average platelet count (pre-implant = 473 ± 56 K/µl and post-implant = 331 ± 62 K/µl), and average hematocrit (pre-implant = 31 ± 2% and post-implant = 29 ± 2%) were normal at all measured time-points for each test animal in acute and chronic experiments. There were no changes in measures of hepatic function (ALP, ALT) or renal function (creatinine) from pre-Symphony implantation values. The necropsy examination showed no signs of thrombus formation in the Symphony or end organs. CONCLUSIONS: These data suggest that the designed Symphony has good washing characteristics without persistent areas of blood stagnation sites during the entire pump cycle, and has a low risk of hemolysis and thrombus formations.

Glasgow coma scale does not predict outcome post-intra-arterial treatment for basilar artery thrombosis.

BACKGROUND AND PURPOSE: Evidence to guide patient selection for IA therapy in acute basilar artery thrombosis is lacking. The GCS is frequently used as a selection criterion, based on the view that higher GCS correlates with better neurologic outcome. This view has not been systematically studied. We hypothesize that low GCS does not correlate with poor outcome and that it should not preclude IA therapy. MATERIALS AND METHODS: We included 40 consecutive patients with basilar artery thrombosis treated with IA therapy. Clinical characteristics, GCS, time to intervention, and postprocedural TIMI scores were collected. Recanalization was defined as TIMI grade 2 or 3; clinical outcome was measured by 90-day mRS. RESULTS: Median patient age was 63.5 years. Most presented with gaze palsies (67.5%) or hemiparesis (45%). Median GCS was 9, the median time to intervention was 7.2 hours, and recanalization rate was 82.5%. Good neurologic outcome (mRS ≤ 1) occurred in 30%. There was no correlation between GCS and 90-day mRS (Spearman ρ - 0.174, P = .283). Equal numbers of patients with good neurologic outcome of mRS ≤ 1 (n = 12) had a GCS of ≤6 or >6. In those with GCS ≤ 6 for >3 hours, 33.3% had good neurologic outcome-a similar rate to that of the overall cohort. Statistical significance was demonstrated between time to IA therapy within 6 hours and mRS ≤ 2. CONCLUSIONS: Low GCS score did not correlate with poor neurologic outcome in patients with acute basilar artery thrombosis managed with IA therapy. It is not appropriate to exclude patients from IA therapy on the basis of low GCS.

Does intra-arterial thrombolysis have a role as first-line intervention in acute ischaemic stroke?

Minimization of the clinical impact of acute ischaemic stroke depends largely on prompt restoration of blood flow to underperfused regions of the brain. Intravenous thrombolysis (IVT) is currently the first-line intervention for acute ischaemic stroke, with proven efficacy in randomized controlled trials. There are several major limitations associated with IVT, in particular, the relatively poor outcomes in large artery occlusions. A major emerging modality in acute stroke management is intra-arterial thrombolysis (IAT), whereby clot-retrieval or thrombolytics are applied under angiographic guidance to the site of the clot. Strong arguments exist for the use of IAT as first-line ischaemic stroke management in preference of IVT, especially with large intracranial artery occlusion. Despite these arguments, the lack of data from randomized controlled studies in IAT means that it is appropriate to continue the current practice of IVT as first-line treatment for the majority of acute ischaemic strokes at this stage. Advanced neuroimaging techniques, in particular a 'multimodal' computed tomography (CT) approach combining non-contrast CT, CT angiography and perfusion CT, may serve as a valuable triage tool for patient selection. Ongoing research is required in endovascular approaches to stroke; in particular, randomized controlled trials with a focus on clinical outcomes and tackling the inherent delays between symptom onset and treatment.

Bone subtraction CT angiography for the detection of intracranial aneurysms.

INTRODUCTION: The aim of the study was to retrospectively analyse the accuracy of CT angiography (CTA) of the Circle of Willis and a prototype bone subtraction CT angiogram (BSCTA) compared with digital subtraction angiography (DSA) in the detection of intracranial aneurysms. METHODS: A total of 36 patients with suspected subarachnoid haemorrhage who had CTA scans that had matching DSA studies between November 2005 and December 2006 were retrospectively reviewed by two experienced neurointerventionalist. Three-dimensional volume-rendered (3D VR) CTA and BSCTA were reviewed, followed by review of the source data in multi-planar reformats (MPRs). The results were then assessed for sensitivity and specificity compared with the gold standard DSA. Time taken to review the studies, visibility of the ophthalmic, posterior communicating arteries, superior cerebella artery, posterior cerebral artery on the 3D VR BSCTA and CTA were analysed. BSCTA was assessed for residual bone and artificial stenosis. Further, the aneurysms were analysed for suitability of endovascular treatment versus surgical treatment based on CTA and BSCTA with MPR and 3D VR. RESULTS: CTA 3D VR sensitivity and specificity was 94 and 80%, respectively. CTA MPR sensitivity and specificity was 100% and 90%, respectively. When both CTA 3D VR and MPR images were combined the sensitivity and specificity was 100 and 90%, respectively. BSCTA 3D VR sensitivity and specificity was 91 and 90%, respectively, and the MPR sensitivity and specificity was 97 and 90%, respectively. When both BSCTA 3D VR and MPR images were combined the sensitivity was 97% with a specificity of 90% Overall, an 84% correlation was found between both CTA and BSCTA when compared with DSA for assessing for suitability of endovascular treatment versus surgical treatment. A statistically significant difference was shown between the time taken to review the CTA and BSCTA (P < 0.001 confidence interval 3.1-3.9 min). CONCLUSION: In this study there was no significant difference between the diagnostic ability of BSCTA compared with CTA. Importantly, both CTA and BSCTA had high sensitivities and specificities compared to DSA.

Targeting mTOR-dependent tumours with specific inhibitors: a model for personalized medicine based on molecular diagnoses.

Cancer cells are characterized by aberrant growth arising from deregulated signalling pathways. The mammalian target of rapamycin (mTOR) pathway integrates multiple growth signals coming from both intracellular and extracellular cues. In this short review, we summarize what is known about the efficacy of targeting the mTOR pathway to treat cancer patients, and we explain the rationale behind promising new inhibitors that could show more potent tumour growth inhibition than did the first generation of these drugs.

Iliocaval arteriovenous fistula presenting with multiple organ failure.

Iliac arteriovenous fistulas are an uncommon condition, which may be spontaneous or traumatic in nature. Such fistulas classically present with a triad of high-output cardiac failure, pulsatile abdominal mass with a bruit and unilateral leg ischaemia or venous congestion. We describe a case of an iliocaval fistula secondary to rupture of a common iliac artery aneurysm, with an unusual presentation of multiple organ failure, masquerading as sepsis. We describe the CT findings of iliocaval fistula, which was the means of diagnosis in this study.

Unusual presentation of perirenal lung metastases.

Lung cancer is not commonly known to metastasize to the perirenal space, with only five such cases previously published. We present an unusual case of perirenal lung metastases manifesting as diffuse perinephric stranding which to our knowledge has not been described before.