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<h3></h3> We present a 50-year-old lady with 6-months’ history of episodes of feeling weak with legs giving way triggered by sudden change of position or head-turning and no loss of consciousness. She had left tinnitus for years and one year worsening migraines with fortification spectra, visual blurring, and vertigo. ENT made a diagnosis of vestibular migraines. Her neurological examination was normal and attempted provocation of attacks with sudden changes in position and Dix-Hallpike was unsuccessful. Brain MRI revealed a large lesion obstructing foramina of Luschka-Magendie giving rise to obstructive hydrocephalus. Neuro-ophthalmology review showed bilateral papilledema and no evidence of Parinaud’s syndrome (no convergence retraction nystagmus or tectal pupils). Tumour biomarkers (bHCG-AFP-AlkPh-LDH) and body CT scan were normal. She underwent urgent CSF diversion. MDTs confirmed radiological diagnosis of epidermoid cyst awaiting debulking. Episodic headaches/vertigo with head-turning are described in Bruns syndrome manifesting as abrupt headaches, vertigo, vomiting provoked by changes in head position due to intermittent obstructive hydrocephalous (mass lesion and ball-valve mechanism). We propose patient’s acute episodes of lower limb weakness were similar phenomenon highlighting importance of imaging in stereotypical attacks after triggers.

GATA-3 plays a critical role in allergic diseases by regulating the release of cytokines from Th2 lymphocytes. However, the molecular mechanisms involved in the regulation of GATA-3 in human T lymphocytes are not yet understood. Using small interfering RNA to knock down GATA-3, we have demonstrated its critical role in regulating IL-4, IL-5, and IL-13 release from a human T cell line. Specific stimulation of T lymphocytes by costimulation of CD3 and CD28 to mimic activation by APCs induces translocation of GATA-3 from the cytoplasm to the nucleus, with binding to the promoter region of Th2 cytokine genes, as determined by chromatin immunoprecipitation. GATA-3 nuclear translocation is dependent on its phosphorylation on serine residues by p38 MAPK, which facilitates interaction with the nuclear transporter protein importin-alpha. This provides a means whereby allergen exposure leads to the expression of Th2 cytokines, and this novel mechanism may provide new approaches to treating allergic diseases.

Measurement of fractional exhaled nitric oxide in exhaled air is an exciting innovative technique that gives new insights in to the pathophysiology of lung disease and asthma in particular, with many potential clinical applications. Careful standardisation of measurement techniques will facilitate the use of this new measurement in paediatric respiratory medicine: this Task Force was set up for this purpose. Methodologies, for use in all age groups, are already available and there are abundant questions relating to interpretation and application of fractional exhaled nitric oxide waiting to be addressed. Noninvasiveness and instantaneous results potentially make it a suitable monitoring instrument for use in children. Exhaled nitric oxide measurement has definitely found its way into clinical research in paediatric respiratory medicine. Evidence for clinically-useful applications is accumulating, and the merits of this new technique must now be demonstrated in larger studies, using standardised methodology in an appropriate setting.

Background In the GLOBAL LEADERS trial, the intention-to-treat (ITT) effect of ticagrelor monotherapy after 1 month of dual antiplatelet therapy (DAPT) was not superior to that of 12-month DAPT followed by aspirin alone in the prevention of 2-year all-cause mortality or new Q-wave myocardial infarction (MI) after coronary stenting. Intention-to-treat analyses can be affected by incomplete protocol adherence. We present a pre-specified per-protocol analysis. Purpose To determine whether 1 month of ticagrelor plus aspirin followed by 23 months of ticagrelor monotherapy is superior to 12 months of DAPT followed by aspirin alone in the per-protocol population of the GLOBAL LEADERS (NCT01813435). Methods The GLOBAL LEADERS compared two antiplatelet strategies after drug-eluting stenting for stable coronary artery disease or acute coronary syndromes. Per-protocol population consisted of randomized patients fulfilling enrollment criteria and receiving protocol-mandated treatment. Adherence to the allocated antiplatelet therapy was evaluated at discharge, 30 days, and 3, 6, 12, 18, and 24 months, with non-adherence reasons categorized following a hierarchical approach. A protocol-deviation was defined in the case of high perceived bleeding/thrombotic risk, a medical decision without evident clinical reason, patients unwilling to take study drugs, prescription error, logistical issues, unclear reasons. Baseline characteristics, including (but not limited to) age, sex, diabetes, prior PCI, were used to construct time-varying inverse probabilities for not deviation from the protocol to reconstruct a study population with no protocol-deviations. Protocol deviators were artificially censored at the time at which they deviated. The primary endpoint was the composite of 2-year all-cause mortality or non-fatal new Q-wave MI. We used a weighted pooled logistic regression to estimate the per-protocol rate ratio (RR) of experimental vs. control treatment for the primary endpoint. Results Of the 15,968 randomized patients, 805 out of 7,980 (10.1%) in experimental group and 537 out of 7,988 (6.7%) in control group were classified as protocol deviators and artificially censored by month 12, not contributing events in the second year. The events for the adherence-adjusted analysis were 279 in experimental group and 325 in control group (25 and 24 less than in ITT analysis, respectively). The estimated adherence-adjusted RR was 0.87 (95% CI: 0.74–1.02; p=0.09), comparable to the ITT RR (0.87; 95% CI: 0.75–1.01; p=0.07). Conclusion At per-protocol analysis, ticagrelor monotherapy after 1 month of DAPT was not superior to conventional treatment, in line with the previously reported ITT effect. Similar per-protocol and ITT effects can be accounted for similar per-protocol and ITT populations, as a substantial proportion of patients were non-adherent due to clinically grounded reasons (anticipated in the protocol) and, accordingly, not considered as protocol deviators. Funding Acknowledgement Type of funding source: Other. Main funding source(s): GLOBAL LEADERS was sponsored by the European Clinical Research Institute, which received funding from Biosensors International, AstraZeneca, and the Medicines Company.

Objectives. This study was undertaken to compare coronary angioscopy with angiography for the detection of intimal dissection and intracoronary thrombus. Background. It has been demonstrated previously that coronary angioscopy provides more intravascular detail than cineangiography. Both imaging methods have to be compared directly to assess the additional diagnostic value of angioscopy. Methods. The angiograms and videotapes of 52 patients who had undergone angioscopy were reviewed independently by two observers unaware of other findings. Classic angiographic definitions were used for dissection and thrombus. Angioscopic dissection was defined as visible cracks or fissures on the lumen surface or mobile protruding structures that are contiguous with the vessel wall. Angioscopic thrombus was defined as a red, white or mixed red and white intraluminal mass. Results. Angiography and angioscopy were in agreement in 40.4% of cases in the absence of thrombus and in 11.5% in the presence of thrombus. No fewer than 25 (48.1%) angioscopically observed thrombi remained undetected at angiography. With angioscopy as the standard, although the specificity of angiography for thrombus was 100%, sensitivity was very low at 19%. Angioscopic dissection was present in 40 patients (76.9%) versus angiographic dissection in 15 patients (28.8%). With regard to dissection, there was no correlation between the two imaging methods (rΦ= 0.15, p = 0.29). Conclusions. Coronary angiography underestimates the presence of intracoronary thrombus. Angioscopy and angiography are complementary techniques for detecting and grading intima1dissections.

The composition and morphology of an atherosclerotic lesion are currently considered more important determinants of acute coronary ischemic syndromes that the degree of stenosis. When a lesion is unstable, it can rupture and cause an acute thrombotic reaction. An unstable plaque can be characterized by a lipid core that is covered by a thin fibrous cap, which has been locally weakened by inflammatory cells. Intravascular Ultrasound Palpography is an intravascular ultrasound based technique that is capable to measure the local strain in coronaries and atherosclerotic plaque. This strain is induced by varying intraluminal pressure. This lecture will show principles of the technology and how this technology is used in clinical trials. Results from a trial with traditional lipid lowering treatment (IBIS1) and from a trial on the efficacy of a new medication (IBIS2) will be presented. Furthermore the potential of Intravascular Ultrasound Modulography will be discussed. This work is financially supported by the Dutch Technology Foundation, The Dutch Heart Foundation and a research grants from Volcano Corporation and Glaxo Smith Kline

The significant interaction between major infection and 5-year mortality after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) for complex coronary artery disease (CAD) was observed previously. However, the very long-term outcomes beyond 5 years remains unclear.This is a subgroup analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the randomized SYNTAX trial comparing PCI versus CABG in patients with three-vessel disease (3VD) or left-main CAD (LMCAD). Out of 1517 patients enrolled in the SYNTAX trial with available survival status from 5 to 10 years, 140 patients had experienced major infections and survived at 5 years (major infection group). From 5 to 10 years, the mortality of major infection group was 19.8% whereas the mortality of no major infection group was 15.1% (p = 0.157). After the adjustment of other clinical factors, the risk of mortality from 5 to 10 years did not significantly differ between major infection and no major infection groups (HR: 1.10; 95% CI: 0.62-1.96; p = 0.740). When stratified by the presence or absence of periprocedural major infections, defined as a major infection within 60 days after index procedure, there was also no significant difference in 10-year mortality between two groups (30.8% vs. 24.5%; p = 0.057).Despite the initial association between major infections and 5 years mortality, postprocedural major infection was not evident in the 10 years follow-up, suggesting that the impact of major infection on mortality subsided over time beyond 5 years.SYNTAXES ClinicalTrials.gov reference: NCT03417050 SYNTAX ClinicalTrials.gov reference: NCT00114972.

Chronic obstructive pulmonary disease (COPD) patients have an increased number of T cells within their lungs.It is unknown whether these T cells, remain there forever or if there is a continuous turnover from the blood.In the adult, there is a significant T lymphocytopoiesis from the thymus producing cells known as recent thymic emigrants (RTEs).T cell receptor excision circles (TREC) are a marker of RTEs.We investigated the number of TREC in blood from patients with untreated stable, mild to moderate COPD (n=6) compared with age-matched smokers with normal lung function (n=6) and nonsmokers (n=8).The results showed variable expression of TREC in each subject group and no significant difference between TREC expressions in any group of subjects.Changes in T-cell numbers in the lung of stable COPD patients may reflect prolonged survival or proliferation of these cells within the lung rather than continuous recruitment from the blood.