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Deep-seated brain tumours represent a unique neurosurgical challenge as they are often surrounded by eloquent structures. We describe a minimally invasive technique using tubular retractors and intraoperative neurophysiology monitoring for open biopsy of a deep-seated lesion surrounded by the corticospinal tract. We used preoperative functional mapping with diffusion tensor imaging tractography and navigated transcranial magnetic stimulation to identify a safe surgical corridor. We also used 5-Aminolevulinic Acid induced fluorescence to identify the lesion intraoperatively and optimize tissue samples obtained for histopathological diagnosis. We found the use of these tools improved the safety of surgery and reduced the risk of surgical morbidity.

Background Diffuse gliomas have an increased biological aggressiveness across the World Health Organization (WHO) grading system. The implications of glioma grading on the primary motor cortex (M1)-corticospinal tract (CST) excitability is unknown. Objective To assess the excitability of the motor pathway with navigated transcranial magnetic stimulation (nTMS). Methods Retrospective cohort study of patients admitted for surgery with diffuse gliomas within motor eloquent areas. Demographic, clinical, and nTMS-related variables were collected. The Cortical Excitability Score (CES 0 to 2 according to the number of abnormal interhemispheric resting motor threshold (RMT) ratios) was calculated for patients where bilateral upper and lower limb mapping was performed. Results A total of 45 patients were included: 9 patients had a low-grade glioma and 36 patients had a high-grade glioma. The unadjusted analysis revealed an increase in the latency of the motor evoked potential of the lower limb with an increase of the WHO grade (P = .038). The adjusted analysis confirmed this finding (P = .013) and showed a relation between the increase in the WHO and a decreased RMT (P = .037) of the motor evoked responses in the lower limb. When CES was calculated, an increase in the score was related with an increase in the WHO grade (unadjusted analysis-P = .0001; adjusted analysis-P = .001) and in isocitrate dehydrogenase (IDH) wild-type tumors (unadjusted analysis-P = .020). Conclusion An increase in the WHO grading system and IDH wild-type tumors are associated with an abnormal excitability of the motor eloquent areas in patients with diffuse gliomas.

Background Lesions within the primary motor cortex (M1) and the corticospinal tract (CST) represent a significant surgical challenge with a delicate functional trade-off that should be integrated in the overall patient-centered treatment plan.Methods Patients with lesions within the M1 and CST with preoperative cortical and subcortical mapping (navigated transcranial magnetic stimulation [nTMS] and tractography), intraoperative mapping, and intraoperative provisional histologic information (smear with and without 5-aminolevulinic acid [5-ALA]) were included. This independently acquired information was integrated in a decision-making process model to determine the intraoperative extent of resection.Results A total of 10 patients (6 patients with metastatic precentral tumor; 1 patient with grade III and 2 patients with grade IV gliomas; 1 patient with precentral cavernoma) were included in the study. Most of the patients (60%) had a preoperative motor deficit. The nTMS documented M1 invasion in all cases, and in eight patients, the lesions were embedded within the CST. Overall, 70% of patients underwent gross total resection; 20% of patients underwent near-total resection of the lesions. In only one patient was no surgical resection possible after both preoperative and intraoperative mapping. Overall, 70% of patients remained stable postoperatively, and previous motor weakness improved in 20%.Conclusion The independently acquired anatomical (anatomical MRI) and functional (nTMS and tractography) tests in patients with CST lesions provide a useful guide for resection. The inclusion of histologic information (smear with or without 5-ALA) further allows the surgical team to balance the potential functional risks within the global treatment plan. Therefore, the patient is kept at the center of the informed decision-making process.

Background Patient-reported experience measures (PREMs) are a unique measure of experience of patients which can help address the quality of care of the patients. Objective Our aim of the study is to collect quality of care outcomes with our newly navigated transcranial magnetic stimulation patient-reported experience measure (nTMS-PREMs) questionnaire among neurosurgical patients undergoing nTMS. Methods A single-centre prospective nTMS-PREMs 19-item questionnaire study was performed between February 2018 and December 2018 on patient referred for nTMS at our hospital. The Data was analysed using Likert scale, linear and logistic regression using statistical software (STATA 13.0®). Results Fifty patient questionnaires were collected (30 males, 20 females, mean age of 47.6 ± 2.1 years) among which 74% of patients underwent both motor and language mapping with a mean duration of 103.3 ± 5.1 min. An overall positive response was noted from the results of the questionnaire, tiredness and anxiety being the common effects noted. Patients with the left-sided disease appreciated more the conditions provided in our laboratory (Q4, p = 0.040) and increasing age was related to less confidence and trust (Q6, p = 0.038) in the staff performing the exam. Younger patients tolerated nTMS better than older patients (> 65 years). PubMed literature search resulted in no relevant articles on the use of PREMs in nTMS patients. Conclusion nTMS is a well-tolerated non-invasive tool and nTMS-PREMS provides a promising role in identifying the unmet needs of the patients and improving the quality of their care.

BACKGROUND This study assesses different technologies for detecting epidermal growth factor receptor (EGFR) mutations from circulating tumor DNA in patients with EGFR T790M-positive advanced non-small cell lung cancer (NSCLC) from the AURA3 study (NCT02151981), and it evaluates clinical responses to osimertinib and platinum-pemetrexed according to the plasma T790M status. METHODS Tumor tissue biopsy samples were tested for T790M during screening with the cobas EGFR Mutation Test (cobas tissue). Plasma samples were collected at screening and at the baseline and were retrospectively analyzed for EGFR mutations with the cobas EGFR Mutation Test v2 (cobas plasma), droplet digital polymerase chain reaction (ddPCR; Biodesix), and next-generation sequencing (NGS; Guardant360, Guardant Health). RESULTS With cobas tissue test results as a reference, the plasma T790M positive percent agreement (PPA) was 51% (110 of 215 samples) by cobas plasma, 58% (110 of 189) by ddPCR, and 66% (136 of 207) by NGS. Plasma T790M detection was associated with a larger median baseline tumor size (56 mm for T790M-positive vs 39 mm for T790M-negative; P

AIMS 5-ALA (Gliolan©) is a valuable surgical tool used predominantly in high grade tumours, which utilises tissue fluorescence to improve the visualisation of the brain-tumour interface. This ensures safe maximal resection, while preserving healthy brain. While Gliolan© use in low grade tumours has previously been reported with variable results, reports of its use and success in the context of SEGA are extremely rare. This report highlights the use of Gliolan© in a patient presenting with a Subependymal Giant Cell Astrocytoma (in a background of tuberous sclerosis), facilitating maximal safe resection and preserving eloquent tissue. METHOD Tumour resection was performed with pre-operative DTI-fiber tracking and mapping. A transsulcal minimal invasive parafascicular approach (tsMIPS) was carried out with assistance of NICO BrainPath© tubular retractor system (60x13.5), neuronaviagtion, Gliolan©, intra-operative neuro monitoring (IONM), and ultrasound guidance RESULTS The tumour was found to have both bright and pale fluorescence in the cystic and solid components respectively. Resection was limited to the soft cystic component only, as the solid tumour component showed anatomical attachment to the subgenual area and the fornix. No fluorescence was perceived at the end of resection. The patient made a good recovery with no post-operative deficits. Histopathology confirmed subependymal giant cell astrocytoma (SEGA, WHO grade I). No adjuvant treatment was required CONCLUSION This reports suggests 5-ALA may be beneficial in the safe resection of SEGAs. Further studies and technological advances in the area of photodynamics, imaging, and intra-operative mapping may be helpful to fully evaluate the efficacy of 5-ALA in SEGAs and other low-grade tumours.

Background Lesions within the corticospinal tract (CST) represent significant surgical challenge with a delicate functional trade-off that should be integrated in the overall patient-centred treatment plan. Methods Patients with lesions within the CST with preoperative cortical and subcortical mapping (nTMS and tractography), intraoperative mapping and intraoperative provisional histological information (smear +- 5-ALA) were included. This independently acquired information was integrated in a decision-making process model to determine the intraoperative extent of resection. Results 10 patients (6 patients with metastatic precentral tumour; 1 patient with Grade III and 2 patients with grade IV gliomas; 1 patient with precentral vascular malformation) were included in the study. Majority of the patient had pre-operative motor deficit (60%). 50% patients underwent gross total resection and 40% patients underwent near total resection of the lesions. In only one patient, no surgical resection was possible after both pre-operative and intraoperative mapping. 70% of patients remained stable postoperatively and 20% improved from previous motor weakness. Conclusion The independently acquired anatomical (anatomical MRI) and functional (nTMS and tractography) in patients with CST lesions provide a more accurate guide for resection. The inclusion of the histological information (smear +- 5-ALA) further allows the surgical team to balance the potential functional risks within the global treatment plan. Therefore, the patient is kept at the centre of the informed decision making process.

Introduction Osimertinib is an oral, central nervous system–active, EGFR tyrosine kinase inhibitor (TKI) for the treatment of EGFR T790M–positive advanced NSCLC. Here we have evaluated EGFR mutation frequencies in two phase II studies of osimertinib (AURA extension and AURA2). Methods After progression while receiving their latest line of therapy, patients with EGFR mutation–positive advanced NSCLC provided tumor samples for mandatory central T790M testing for the study selection criteria. Tumor tissue mutation analysis for patient selection was performed with the Roche cobas EGFR Mutation Test (European Conformity–in vitro diagnostic, labeled investigational use only) (Roche Molecular Systems, Pleasanton, CA). Patients should not have been prescreened for T790M mutation status. The cobas test results were compared with those of the MiSeq next-generation sequencing system (Illumina, San Diego, CA), which was used as a reference method. Results Samples from 324 and 373 patients screened for AURA extension and AURA2, respectively, produced valid cobas test results. The T790M detection rates were similar between AURA extension and AURA2 (64% and 63%, respectively). The pooled T790M rate was 63%, with no difference by ethnicity (63% for Asian and non-Asian patients alike) or immediately prior treatment with an EGFR TKI (afatinib, 69%; erlotinib, 69%; and gefitinib, 63%). A higher proportion of patients had T790M detected against a background of exon 19 deletions versus L858R mutation (73% versus 58% [ p = 0.0002]). In both trials the cobas test demonstrated high sensitivity (positive percent agreement) and specificity (negative percent agreement) for T790M detection when compared with the next-generation sequencing reference method: positive percent agreement of 91% versus 89% and negative percent agreement of 97% versus 98%. Conclusions In both trials, the rate of detection of T790M mutation in patients with advanced NSCLC was approximately 63% and was unaffected by immediately prior treatment with an EGFR TKI or ethnicity.

Introduction Surgical site infections (SSIs) are of profound significance in neurosurgical departments, resulting in high morbidity and mortality. There are limited public data regarding the incidence of SSIs in neurosurgery. The aim of this study was to determine the rate of SSIs (particularly those requiring reoperation) over a seven-year period and identify factors leading to an increased risk. Methods An age matched retrospective analysis was undertaken of a series of 16,513 patients at a single centre. All patients who required reoperation for suspected SSIs within a 7-year period were identified. Exclusion criteria comprised absence of infective material intraoperatively and patients presenting with primary infections. Clinical notes were reviewed to confirm presence or absence of suspected risk factors. Results Of the 16,513 patients in the study, 1.20% required at least one further operation to treat a SSI. Wound leak (odds ratio [OR]: 27.41), dexamethasone use (OR: 3.55), instrumentation (OR: 2.74) and operative duration >180 minutes (OR: 1.85) were statistically significant risk factors for reoperation. Conclusions This is the first UK study of such a duration that has documented a SSI reoperation rate in a cohort of this size. Various risk factors are associated with the development of SSIs, making it essential to have robust auditing and monitoring of high risk patients to ensure excellent standards of healthcare. Departmental and public registers to record all SSIs may be beneficial, particularly for those treated solely by general practitioners, allowing units to address potential risk factors prior to surgical intervention.

OBJECTIVES: Surgery for lesions in eloquent brain areas is challenging due to the underlying risk of causing permanent neurological deficits. To date, Direct Cortical Stimulation (DCS) and intra-operative neuro-monitoring (IOM) represent the gold standard in minimising such risk. Recently, Transcranial Magnetic Stimulation (TMS) has emerged as a mapping tool that assists in optimising surgical planning. The aim of this study is to validate our TMS findings against DCS. METHODS: Retrospective single-centre analysis of 35 adult patients with TMS, DCS and IOM for space occupying lesion (SOL) at King’s College Hospital from February 2017 to February 2018. Patients with arteriovenous malformation were excluded from analysis. We collected data on patient demographics, tumour entity/location, extent of resection (EoR), change of surgical strategy, neurological outcome, and correlated TMS with DCS/IOM. RESULTS: 24/35 patients (68.6%) had pre-operative motor mapping and 11/35 (31.4%) were mapped for language. Histopathology demonstrated a glioma in 85.7% of patients (high grade n=24; low grade n=6) and metastasis (n=2), cavernoma (n=1) and other cases (n=2). TMS resulted in a change of surgical strategy in 34.3% (craniotomy size n=7; surgical pathway n=3; EoR n=1; surgical indication n=1). Sensitivity of TMS for language was 70.6% with a positive predictive value of 60.0% (n=9). TMS motor mapping correlated with DCS/IOM in all cases with snapshot hotspot conformity of 100% (n=5). A total of 12 patients had a new transient neurological deficit which resolved/significantly improved except for one case (expressive dysphasia). CONCLUSIONS: TMS is a non-invasive, safe and effective adjunct in surgery planning in eloquent brain areas. It is reliable in predicting M1/motor mapping and shows promising results for language mapping. Larger randomised controlled trials are needed to validate these findings.

Sylvian fissure meningiomas (SFMs) represent a rare subgroup of nondural-based tumors arising from the meningothelial cells within the arachnoid of the Sylvian fissure. SFMs are more frequent in young males, usually manifest with seizures and display the same radiological features of meningiomas in other locations. Although the absence of dural attachment makes these tumors suitable for a complete resection, their anatomical relationships with the middle cerebral artery branches have impaired its achievement in half of them. To the best of our knowledge, only five atypical WHO grade II SFMs have been previously described. We provide a literature review of SFMs WHO grades I–II and discuss common characteristics and surgical challenges we found in a similar case.

Background Surgery for lesions in eloquent brain areas remains challenging owing to the risk of permanent neurological deficits. To date, direct electrical stimulation (DES) and intraoperative neuromonitoring represent the reference standard. Recently, navigated transcranial magnetic stimulation (nTMS) has emerged as a mapping tool to optimize surgical planning. Our aim was to correlate nTMS with the intraoperative findings and assess its effects on surgical decision-making. Methods We retrospectively reviewed our series of patients who had undergone craniotomy for removal of a brain tumor at our institution with preoperative nTMS, intraoperative neuromonitoring, and DES from February 2017 to February 2018. Demographic data, tumor entity and location, extent of resection, change in surgical approach, and neurological outcome were collected. Results Of 35 patients, 24 (68.6%) had undergone preoperative motor mapping and 11 (31.4%) had undergone mapping for language. Histopathological examination demonstrated glioma in 88.6% (high grade, n = 24; low grade, n = 6), metastasis (n = 2), epidermoid cyst (n = 1), and cavernoma (n = 1). nTMS resulted in change in the surgical strategy in 31.5% (craniotomy size, n = 7; access pathway, n = 3; surgical indication, n = 1). The specificity of nTMS for language was 66.7%, with a negative predictive value of 74.1%. nTMS motor mapping correlated with DES in all cases, with a mean abductor pollicis brevis hotspot distance of 3.50 ± 0.66 mm (n = 9). Conclusions nTMS is a safe, noninvasive adjunctive tool for preoperative mapping of brain tumors in eloquent areas. Furthermore, nTMS can influence the surgical decisions in up to one third of patients in our experience.

Introduction Navigated Transcranial Magnetic Stimulation (nTMS) is a non-invasive adjunct used in surgical planning for lesions in eloquent brain. However, its patient tolerability and effect on their overall healthcare experience is still unknown. To our knowledge, there is no other literature available evaluating patient experience with nTMS. Methods A single-institution prospective cohort study carried out between February 2018 and December 2018 at King’s College Hospital. All patients were supplied with a PREMs-TMS questionnaire to evaluate the different domains of the nTMS experience. Results Feedback was obtained from 50 patients. 26% of patients underwent motor mapping (MM), whilst 74% underwent both motor and language mapping (MLM). The former group reported a better overall experience (p=0.020). The mean exam duration was 103.3±5.1 min (MM 85.8±6.1 min; MLM 106.9±5.9 min). The whole experience of nTMS received positive feedback (94%), particularly with confidence in the staff (95%). Unsurprisingly, the exam domain received a poorer rating (70% as good) with significant anxiety and pain reported in 26% and 24% of patients respectively. None of the studied variables influenced the way patients rated the overall experience of nTMS (p>0.05). Conclusions nTMS is a non-invasive investigative tool, which allows patients to better understand their condition and symptoms related to their lesion. Serial assessment and feedback using a PREM tool, can only improve and enhance this experience. Departmental collaboration may be useful in comparing patient experience with nTMS in different centres.

Background Navigated transcranial magnetic stimulation (nTMS) is a nonsurgical mapping technique used in mapping of motor and language eloquent areas within and/or surrounding brain tumors. Previous reports support this as a safe technique with minor side effects associated with minor headaches and discomfort around the stimulation area. Currently there are no published reports concerning the accuracy and safety of this procedure in patients with a titanium cranioplasty in situ. Case Presentation A 59-year-old lady was diagnosed with a recurrent glioma in the context of increasing seizure frequency, left-sided numbness, and weakness. She was diagnosed with a World Health Organization grade 2 oligodendroglioma 10 years before her presentation, which was initially treated with radiotherapy and then surgical resection of this lesion 5 years later. The procedure was complicated with a wound infection, treated with a craniectomy and wound washout, followed by a titanium cranioplasty. Before proceeding with surgery for recurrence, nTMS was performed for motor mapping. No complications were identified. She underwent a craniotomy for tumor resection with aminolevulinic acid HCl (Gliolan), and the tumor was completely removed. Intraoperatively, the direct cortical stimulation correlated with the preoperative nTMS. The pathologic diagnosis on recurrence was an anaplastic oligodendroglioma grade III, and the patient is currently undergoing adjuvant chemotherapy. Conclusion This report confirms that nTMS is a safe and accurate procedure in patients who have a titanium cranioplasty in situ.

Background: Intradural disc herniations (IDH) are rare, particularly in the cervical spine, where they account for less than 5% of all discs. Adhesions between the ossified/calcified posterior longitudinal ligament (OPLL), dura, and ossified/calcified disc herniations increase the complexity of resecting these cervical lesions. Case Description: A 42-year-old male presented with a rapidly progressive cervical myelopathy over a 2-month period. This was attributed to an ossified/calcified intradural cervical disc herniation in conjunction with OPLL. The anterior cervical discectomy and fusion (ACDF) resulted in a dural defect but there was no cerebrospinal fluid (CSF) fistula as the arachnoid membrane remained intact. Had there been a CSF leak, it would have warranted both wound-peritoneal (WP) and lumbo-peritoneal shunts (LP). The surgeons should have anticipated that a CSF leak would likely occur prior to performing the ACDF, and should have prophylactically prepared and draped the abdomen for a potential WP, followed by a LP shunt. Three months postoperatively, the patient's proprioceptive deficit improved, and he almost completely recovered motor function. Conclusion: Performing an ACDF for resection of an intradural calcified/ossified disc with OPLL often results in both a dural defect and CSF fistula. As the arachnoid membrane rarely remains intact, the spine surgeon should be prepared to immediately perform both a WP shunt, and subsequently, an LP. In this case, following an ACDF, resection of an intradural ossified disc with OPLL resulted in an isolated dural defect without a CSF fistula and did not require no dural repair or shunting procedures.

External ventricular drain (EVD) insertion is a common neurosurgical procedure with a significant risk of ventriculostomy-associated infections (VAIs), other morbidities and mortality. Several risk factors have been identified but their effect is unclear. Our primary objective was to assess whether recurrent EVD sampling increased the risk of VAIs. The secondary objective was to explore the effect of sampling frequency, duration of EVD stay, presence of cerebrospinal fluid leak and concurrent infections. Ours was a retrospective, single-centre, age-matched, case control study of 83 patients and 249 controls who underwent EVD insertion between 1 January 2010 – 31 December 2016. Patients with primary CNS infections, age under 1 year and death within 5 days of EVD insertion were excluded. Blinded abstractors collected all patient data through the electronic patient record system and regression analysis was used to compare the two groups. Sampling the EVD more than once did not increase the risk of infection (OR 0.47, 95% CI 0.27–0.83, p = 0.01). Risk factors significantly associated with VAI included CSF leak (OR 2.06, 95% CI 1.16–3.67, p = 0.01), concurrent infection (OR 1.85, 95% CI 1.09–3.16, p = 0.02), and an EVD duration of >10 days (OR 2.28, 95% CI 1.24–4.18, p = 0.01). Our findings do not support the notion that increased sampling of EVDs is associated with a higher risk of VAI. CSF leaks, concurrent infection and long-term EVDs are also statistically significant risk factors for infection.

Introduction Tumor biopsies for detecting EGFR mutations in advanced NSCLC are invasive, costly, and not always feasible for patients with late-stage disease. The clinical utility of the cobas EGFR Mutation Test v2 (Roche Molecular Systems, Inc., Pleasanton, CA) with plasma samples from patients with NSCLC at disease progression after previous EGFR tyrosine kinase inhibitor therapy was investigated to determine eligibility for osimertinib treatment. Methods Matched tumor tissue and plasma samples from patients screened for the AURA extension and AURA2 phase II studies were tested for EGFR mutations by using tissue- and plasma-based cobas EGFR mutation tests. Plasma test performance was assessed by using the cobas tissue test and a next-generation sequencing method (MiSeq [Illumina Inc., San Diego, CA]) as references. The objective response rate, measured by blinded independent central review, was assessed in patients receiving osimertinib with a plasma T790M mutation–positive status. Results During screening, 551 patients provided matched tumor tissue and plasma samples. Pooled analysis of the positive and negative percent agreements between the cobas plasma and tissue tests for detection of T790M mutation were 61% and 79%, respectively. Comparing cobas plasma test with next-generation sequencing demonstrated positive and negative percent agreements of 90% or higher. The objective response rate was 64% (95% confidence interval: 57–70) in T790M mutation–positive patients by both cobas tissue and plasma tests (evaluable for response). Conclusions The cobas plasma test detected the T790M mutation in 61% of tumor tissue T790M mutation–positive patients. To mitigate the risk of false-negative plasma results, patients with a negative plasma result should undergo a tissue test where feasible.

ObjectivesMacrophages are central to the inflammatory processes driving rheumatoid arthritis (RA) synovitis. The molecular pathways that are induced in synovial macrophages and thereby promote RA disease pathology remain poorly understood.MethodsWe used microarray to characterise the transcriptome of synovial fluid (SF) macrophages compared with matched peripheral blood monocytes from patients with RA (n=8).ResultsUsing in silico pathway mapping, we found that pathways downstream of the cholesterol activated liver X receptors (LXRs) and those associated with Toll-like receptor (TLR) signalling were upregulated in SF macrophages. Macrophage differentiation and tumour necrosis factor α promoted the expression of LXRα. Furthermore, in functional studies we demonstrated that activation of LXRs significantly augmented TLR-driven cytokine and chemokine secretion.ConclusionsThe LXR pathway is the most upregulated pathway in RA synovial macrophages and activation of LXRs by ligands present within SF augments TLR-driven cytokine secretion. Since the natural agonists of LXRs arise from cholesterol metabolism, this provides a novel mechanism that can promote RA synovitis.

Magnesium is the second most abundant intracellular cation and plays an essential role in neuronal, skeletal and cardiac tissue. Hypomagnesaemia can cause hypocalcaemia by inhibiting parathyroid hormone release and inducing resistance at its receptor sites. Untreated hypomagnesaemia can lead to tetany, recurrent seizures, status epilepticus and life-threatening arrhythmias. Primary hypomagnesaemia with secondary hypocalcaemia (HSH) is a rare metabolic disorder of intestinal magnesium absorption. The condition typically presents in the neonatal period with neuromuscular excitability and seizures refractory to antiepileptic therapy. Early diagnosis and prompt magnesium replacement are essential to prevent death or long-term neurodevelopmental sequelae. Fewer than a hundred cases are reported in the literature. Recent advances have added significantly to our understanding of the genetic basis of HSH. We report the presentation and long-term follow-up of an affected female who was found to have a mutation in the transient receptor potential melastatin 6 (TRPM6) gene, encoding a transient receptor potential cation channel.

Objective To determine whether elevation of a biological marker of inflammation would be a better predictor of bronchopulmonary dysplasia (BPD) development than lung function measurement results. Design Prospective study. Setting Tertiary neonatal intensive care unit. Patients 78 prematurely born infants (median gestational age 29 (range 24–32) weeks) were studied; 39 developed BPD. Interventions BPD was diagnosed as oxygen dependence at 28 days. Main outcome measures Levels of a biological marker of inflammation (carbon monoxide) were assessed by measurement of end-tidal carbon monoxide (ETCO) and lung function by measurement of functional residual capacity (FRC) and compliance (Crs) and resistance (Rrs) of the respiratory system on days 3 and 14 after birth. Possible predictive factors were modelled for BPD and for BPD severity. Results Gestational age, birth weight, ETCO, FRC and Crs results on days 3 and 14 differed significantly between infants who did and did not develop BPD. In multifactorial logistic regression, only birth weight and ETCO results (on day 14) remained significant predictors of BPD with an area under the curve of 0.97. The final multifactorial model for the severity of BPD included those two factors, plus septic episodes. Conclusion These results emphasise the importance of ongoing inflammation in the development of BPD; ETCO levels, rather than lung function test results, were the more accurate predictor of BPD development.

TPS3120Background: Immune checkpoint inhibitor (ICI) containing regimens have significantly improved survival outcomes in first- and second-line non-small cell lung cancer (NSCLC). However, the maj...

Previously, proteomic methods were applied to characterise differentially expressed proteins in microdissected pancreatic ductal adenocarcinoma cells.To report that CapG and a related protein, gelsolin, which have established roles in cell motility, are overexpressed in metastatic pancreatic cancer; and to describe their pattern of expression in pancreatic cancer tissue and their effect on cell motility in pancreatic cancer cell lines.CapG was identified by mass spectrometry and immunoblotting. CapG and gelsolin expression was assessed by immunohistochemical analysis on a pancreatic cancer tissue microarray and correlated with clinical and pathological parameters. CapG and gelsolin levels were reduced using RNA interface in Suit-2, Panc-1 and MiaPaCa-2 cells. Cell motility was assessed using modified Boyden chamber or wound-healing assays.Multiple isoforms of CapG were detected in pancreatic cancer tissue and cell lines. Immunohistochemical analysis of benign (n = 44 patients) and malignant (n = 69) pancreatic ductal cells showed significantly higher CapG staining intensity in nuclear (p0.001) and cytoplasmic (p0.001) compartments of malignant cells. Similarly, gelsolin immunostaining of benign (n = 24 patients) and malignant (n = 68 patients) pancreatic ductal cells showed higher expression in both compartments (both p0.001). High nuclear CapG was associated with increased tumour size (p = 0.001). High nuclear gelsolin was associated with reduced survival (p = 0.01). Reduction of CapG or gelsolin expression in cell lines by RNAi was accompanied by significantly impaired motility.Up regulation of these actin-capping proteins in pancreatic cancer and their ability to modulate cell motility in vitro suggest their potentially important role in pancreatic cancer cell motility and consequently dissemination.

AIM: To establish stable tetracycline-inducible pancreatic cancer cell lines. METHODS: Suit-2, MiaPaca-2, and Panc-1 cells were transfected with a second generation reverse tetracycline-controlled transactivator protein (rtTA2S-M2), under the control of either a cytomegalovirus (CMV) or a chicken β-actin promoter, and the resulting clones were characterised. RESULTS: Use of the chicken (β-actin) promoter proved superior for both the production and maintenance of doxycycline-inducible cell lines. The system proved versatile, enabling transient inducible expression of a variety of genes, including GST-P, CYP2E1, S100A6, and the actin capping protein, CapG. To determine the physiological utility of this system in pancreatic cancer cells, stable inducible CapG expressors were established. Overexpressed CapG was localised to the cytoplasm and the nuclear membrane, but was not observed in the nucleus. High CapG levels were associated with enhanced motility, but not with changes to the cell cycle, or cellular proliferation. In CapG-overexpressing cells, the levels and phosphorylation status of other actin-moduating proteins (Cofilin and Ezrin/Radixin) were not altered. However, preliminary analyses suggest that the levels of other cellular proteins, such as ornithine aminotransferase and enolase, are altered upon CapG induction. CONCLUSION: We have generated pancreatic-cancer derived cell lines in which gene expression is fully controllable.

carotid artery stump pressures of 75yrs (p 75yrs versus 11% in those 75yrs versus 3.4% in those 75yrs was not associated with an increased morbidity or mortality. Intra-operatively reduced carotid stump pressures and MCA velocities were not associated with increased use of shunting or patching. This study supports CE as a safe procedure in the elderly, especially in centres with low complication rates.

A 47 year old Zimbabwean woman presented with gradual onset shortness of breath of two months’ duration. She was breathless at rest, with a non-productive cough, and had had a fever for one week. She had no history of haemoptysis or night sweats but had lost 5 kg in weight over two months. No cardiac symptoms were elicited. She had no previous medical problems, history of smoking, or recent foreign travel. On examination, she had a regular pulse of 122 beats per minute and a respiratory rate of 22 breaths per minute. Her temperature was 39°C and she had an oxygen saturation of 91% on air. There was no palpable lymphadenopathy. Her chest was resonant to percussion, with vesicular breath sounds and no added sounds. Examination of all other systems was normal. A chest radiograph was taken. (1) Describe the chest radiograph findings. (2) What is the differential diagnosis and most likely diagnosis? (3) …