Aintree and Walton Research

Authors: Williams SM, Eleftheriadou A, Alam U, Cuthbertson DJ, Wilding JPH.

Source: Diabetes Ther. 2019 Oct 4.

doi: 10.1007/s13300-019-00705-z. [Epub ahead of print]

PMID: 31583646 [PubMed – as supplied by publisher]

Author(s): Bracewell R.M.; Larner A.J.

Source: European Neurology; Oct 2019 ; p. 1-4

Publication Date: Oct 2019

Publication Type(s): Review

PubMedID: 31574512

Abstract:William Barnett Warrington (1869-1919) was a physician and physiologist working in Liverpool, United Kingdom, at the end of the 19th and beginning of the 20th centuries. His training included periods at the National Hospital for the Paralysed and Epileptic, Queen Square, London, and in the Liverpool laboratory of Charles Scott Sherrington. He investigated structural alterations in nerve cells following various nerve lesions and helped to develop laboratory facilities to support clinical practice through the Pathological Diagnosis Society of Liverpool. His clinical interests were broad, but his main focus seems to have been in disorders of the peripheral nervous system. He published many papers, encompassing descriptions of Charcot-Marie-Tooth disease, brachial plexus paralyses (possibly including neuralgic amyotrophy), and, in the context of the First World War, traumatic peripheral nerve injuries. He may have described cases of Guillain-Barre syndrome prior to the eponymous description but despite being familiar with the technique of lumbar puncture, he did not report cerebrospinal fluid findings in these patients.

Copyright © 2019 S. Karger AG, Basel.

Database: EMBASE

Author(s): Macerollo A.; Limousin P.; Korlipara P.; Foltynie T.; Kilner J.; Edwards M.J.

Source: Frontiers in Neurology; Sep 2019; vol. 10

Publication Date: Sep 2019

Publication Type(s): Article

Abstract:Background and Aims: Pathological high amplitude of beta oscillations is thought as the underlying mechanism of motor symptoms in Parkinson’s disease (PD), in particular with regard to bradykinesia. In addition, abnormality in a neurophysiological phenomenon labeled sensory attenuation has been found in patients with PD. The current study explored the hypothesis that the abnormal sensory attenuation has a causal link with the typical abnormality in beta oscillations in PD. Method(s): The study tested sixteen right-handed patients with a diagnosis of PD and 22 healthy participants, which were matched by age and gender. Somatosensory evoked potentials were elicited through electrical stimulation of the median nerve at the wrist. Electrical activity was recorded at the scalp using a 128 channels EEG. Somatosensory evoked potentials were recorded in 2 conditions: at rest and at the onset of a voluntary movement, which was a self-paced abduction movement of the right thumb. Result(s): Healthy participants showed a reduction of the N20-P25 amplitude at the onset of the right thumb abduction compared to the rest condition (P < 0.05). When patients were OFF medication, they showed mild reduction of the N20-P25 component at movement onset (P < 0.05). On the contrary, they did show greater attenuation of the N20-P25 component at the onset of movement compared to the rest condition when ON medication (P < 0.05). There was no significant evidence of a link between the degree of sensory attenuation and the change in beta oscillations in our cohort of patients. Conclusion(s): These results confirmed a significant link between dopaminergic modulation and sensory attenuation. However, the sensory attenuation and beta oscillations were found as two independent phenomena.

© Copyright © 2019 Macerollo, Limousin, Korlipara, Foltynie, Edwards and Kilner.

Database: EMBASE

Author(s): Benson R.M.; Kirwan J.; Moots R.J.

Source: Clinical and Experimental Rheumatology; Oct 2019

Publication Date: Oct 2019

Publication Type(s): Letter

PubMedID: 31577218

Database: EMBASE

Author(s): Rangarajan K.; Simmons G.; Hamady Z.; Manas D.; Malik H.

Source: European Journal of Surgical Oncology; Nov 2019; vol. 45 (no. 11); p. 2204

Publication Date: Nov 2019

Publication Type(s): Conference Abstract

Abstract:Background: The role of adjuvant therapy for biliary tract cancer is not clearly defined with conflicting results demonstrated across nonrandomized and randomized studies. We report a systematic review and meta-analysis to delineate the effect of AT on overall survival. Method(s): Eligible studies were identified from MEDLINE, EMBASE, Cochrane and PubMed. Studies comparing adjuvant chemotherapy or chemoradiotherapy after curative-intent surgery with curative surgery only for biliary tract cancer were included. Data pertaining to tumours of the gallbladder and bile ducts were included. The primary outcome assessed was overall survival. Random-effects meta-analysis was performed, as well as pooling of unadjusted Kaplan-Meier Curve data. Result(s): 35 studies involving 42,917 patients were analysed. There was a significant improvement in overall survival with any adjuvant therapy after surgery compared with surgery only (HR 0.74; 95% CI, 0.67 to 0.83; P < 0.001). There was a significant benefit for adjuvant therapy in those with margin positive surgery (RR, 0.83; 95% CI, 0.77 to 0.91; P < 0.001) and node-positive disease (RR 0.82; 95% CI 0.76 to 0.89; P < 0.001) Conclusion(s): Our review advocates the use of adjuvant therapy in bile duct cancer after curative intent resection. Further prospective studies are needed to determine the optimal regime and timing of an adjuvant approach.

Copyright © 2019

Database: EMBASE

Author(s): Quinn L.; Palmer D.; Goldring C.; Jones R.; Fenwick S.; Malik H.

Source: European Journal of Surgical Oncology; Nov 2019; vol. 45 (no. 11); p. 2216

Publication Date: Nov 2019

Publication Type(s): Conference Abstract

Abstract:Background: Heterogeneity of actionable mutations remains poorly defined in peri-hilar cholangiocarcinoma with absence of effective targeted therapies. Whole exome sequencing accurately defines protein-coding regions of cancer cell genomes and can identify novel targetable mutations. We completed the first whole exome sequencing study of a Western resected peri-hilar cholangiocarcinoma cohort, to unravel mutational heterogeneity between patients and identify actionable targets. Method(s): Matched tumour and normal bile duct formalin-fixed-paraffin-embedded tissue sections from 40 peri-hilar cholangiocarcinoma resections underwent microdissection increasing tumour cellularity. DNA extraction completed according to Qiagen FFPE DNEasy protocol. DNA quantity and purity were confirmed with Qubit and Nanodrop (Thermofisher). Whole exome sequencing of DNA samples was completed on Illumina HiSeq 2000. Raw sequencing data from matched normal bile duct filtered out non-somatic mutations. Variant calling was cross-referenced to human genome and the Catalogue of Somatic Mutations in Cancer (Sanger Institute) using VarScan and STRELKA software. Result(s): 25 tumour samples yielded high quality DNA for sequencing with 80.65% mapped reads. Median number of total mutations was 1307 (interquartile range 1206 – 1653) with a median number of 334 moderate impact non-synonymous mutations (interquartile range 213 – 454). The median number of high impact mutations including frameshifts and premature stop codons was 53 (interquartile range 46 – 97). Conclusion(s): Peri-hilar cholangiocarcarcinoma demonstrates significant inter-tumoral heterogeneity of mutations in the first Western cohort whole exome sequencing study. Greater numbers of actionable mutations have been identified comparative to published Eastern studies. Significant mutations have completed downstream pathway analysis with considerable implications for targeted therapy development.

Copyright © 2019

Database: EMBASE

Authors: Jenkinson MD, Weber DC, Haylock BJ, Sherratt FC, Young B, Weller M, Bulbeck H, Culeddu G, Hughes DA, Brain A, Das K, Preusser M, Francis P, Gamble C.

Source: J Neurosurg. 2018 Oct;129(4):1104-1105.

doi: 10.3171/2018.6.JNS181418. Epub 2018 Aug 17. No abstract available.

PMID: 30117772 [PubMed – indexed for MEDLINE] Free Article

Authors: Williams SM, Eleftheriadou A, Alam U, Cuthbertson DJ, Wilding JPH.

Source: Diabetes Ther. 2019 Sep 24.

doi: 10.1007/s13300-019-00693-0. [Epub ahead of print] Review.

PMID: 31552598 [PubMed – as supplied by publisher]

Author(s): Haworth J.

Source: Archives of Physical Medicine and Rehabilitation; Oct 2019; vol. 100 (no. 10)

Publication Date: Oct 2019

Publication Type(s): Conference Abstract

Abstract:Objective: To develop a high quality, evidenced-based Complex Rehabilitation Module through collaboration with multi-skilled clinicians. Design(s): Clinician led focus groups described format and content. University collaboration ensured formal accreditation and academic promotion. Setting(s): Specialist Complex Rehabilitation Setting, Liverpool, England. Education sessions hosted within hospital base ensuring clinical practice was at the heart of all learning. Participants (or Animals, Specimens, Cadavers): Cross-section of multidisciplinary professionals from varied health settings. These settings represented the full pathway of care from intensive care through to community support within home environments. Intervention(s): 12 session, educational programme designed to support delivery of holistic rehabilitation. These sessions address the multi-faceted presentations and specialist requirements of patients in complex rehabilitation. Teaching methods included case studies, scenarios, practical sessions, workshops and presentations designed to enable 360 participation. Students are required to critically reflect on literature and their own service/organisation by producing an academic portfolio addressing the modules learning outcomes. Main Outcome Measure(s): Learner Evaluation Forms were designed to collect specific information relevant to the uniqueness of this module and to assess progress towards learning objectives. Data was collated and synthesised informing future development needs. Result(s): 54 multi-disciplinary students completed the module over 3 cohorts 100% reported the module met the defined learning objectives 87.5% would definitely recommend the course 62.5% felt their practice as a clinician changed a lot as a result of attendance. Feedback statements were positive and issues highlighted allowed future modifications. Conclusion(s): This is a unique module that all disciplines and grades can benefit from. It improves collaboration in MDT working which in turn supports effective clinical outcomes and a positive patient experience. Author(s) Disclosures: No author conflict of interest to declare. Key Words: Masters Module, Complex Rehabilitation, Collaboration, Clinical, Academic

Copyright © 2019

Database: EMBASE

Author(s): O’Connor E.; Campbell C.; Southgate L.; Trembath R.; Yip H.Y.; Houlden H.; Hostettler I.C.; Silver N.; Giffin N.J.; Cader M.Z.; Ahmed F.; Davies B.; Matharu M.

Source: Cephalalgia; Sep 2019; vol. 39 (no. 1); p. 1

Publication Date: Sep 2019

Publication Type(s): Conference Abstract

Abstract:Objective: The genetic variation predisposing patients to CH remains elusive. The majority of genetic studies have been association studies in candidate genes with a putative role in CH. We sought to evaluate reported genetic associations with CH, through examination of SNPs in the genes HCRTR2 (rs2653349 and rs3122156), CLOCK (rs12649507) and ADH4 (rs1126671). Also to examine previous GWAS findings in an independent cohort including analysis of candidates rs12668955 within ADCYAP1R1, rs1006417 upstream of the LRFN5 gene and rs147564881 in MME. Method(s): A multicentre study involving six headache centres in the UK between 2016 and 2019. Patients diagnosed with episodic or chronic CH by a neurologist in concordance with the ICHD3b criteria were recruited to the study. DNA was extracted from peripheral blood or saliva and genotyped using the Illumina Infinium Global Screening Array. SNPs of interest were identified and screened for association. Result(s): Overall, approximately 880 cases and 5,000 controls were screened for previously associated variants in candidate genes. Genotype analysis did not identify a statistically significant association between any previously implicated candidate variant and cluster headache Conclusion(s): This is the largest cohort to date examining genetic associations with CH. Our findings do not support previous reports identifying associations between CH and variants in plausible candidates. Whilst this may represent population-specific effects, these findings highlight the importance of independent replication studies, using sufficiently powered datasets and a hypothesis-free approach. It outlines the requirement for multi-centre, collaborative efforts for patient recruitment in future studies.

Database: EMBASE