30 results found
Khatri C, Ward AE, Nepogodiev D, et al., 2021, Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study, BMJ Open, Vol: 11, Pages: 1-10, ISSN: 2044-6055
Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before t
Mirnezami R, Soares A, Chand M, 2019, Enhancing the precision of circular stapled colorectal anastomosis: could powered stapler technology provide the solution?, Techniques in Coloproctology, Vol: 23, Pages: 687-689, ISSN: 1123-6337
The use of circular stapling devices to facilitate low colorectal anastomosis (CRA) was first described in the 1970s. This approach is now standard practice and has consistently demonstrated equivalence in terms of safety and efficacy compared with hand-sewn anastomosis, with the added advantages of shorter anastomotic time and greater reproducibility. Briefly, the key elements of circular stapled CRA comprise: (1) selecting a stapler gun of appropriate size; (2) securing the anvil in the distal end of the mobilised colonic conduit; (3) performing a rendezvous manoeuvre to securely dock the anvil onto the end of the stapler gun, which has been advanced from below; and (4) firing the stapler to complete the anastomosis.While there have been subtle modifications to staple design and configuration, there has been relatively little progress made in circular stapler functionality over the past few decades. Further advances in stapling technology could enhance the precision of CRA with the potential to positively impact on the incidence of anastomotic leakage and on the need for diverting stoma. However, refining the existing design requires the four key steps outlined above to be carefully considered to determine how and/or where the technology can be fine-tuned; sizing and anvil application are obligatory steps, while the rendezvous technique represents an elegant design that lends itself readily to both open and intra-corporeal CRA. The final and arguably most critical step in the technique, namely, discharging the stapler, represents a component in the pathway, where refinement may be both feasible and advantageous, and in this regard, the powered surgical stapler is emerging as a potential solution.Powered surgical stapler devices were first introduced in 2011 and have been applied to a wide variety of clinical applications. More recently, powered circular stapling devices have been developed specifically intended for use in colorectal surgery. We provide a technical
Poynter L, Mirnezami R, Galea D, et al., 2019, Network mapping of molecular biomarkers influencing radiation response in rectal cancer, Clinical Colorectal Cancer, Vol: 18, Pages: e210-e222, ISSN: 1533-0028
IntroductionPre-operative radiotherapy (RT) has an important role in the management of locally advanced rectal cancer (RC). Tumour regression following RT shows marked variability and robust molecular methods are needed with which to predict likely response. The aim of this study was to review the current published literature and employ Gene Ontology (GO) analysis to define key molecular biomarkers governing radiation response in RC.MethodsA systematic review of electronic bibliographic databases (MEDLINE, Embase) was performed for original articles published between 2000 and 2015. Biomarkers were then classified according to biological function and incorporated into a hierarchical GO tree. Both significant and non-significant results were included in the analysis. Significance was binarized based on uni- and multivariate statistics. Significance scores were calculated for each biological domain (or node), and a direct acyclic graph was generated for intuitive mapping of biological pathways and markers involved in rectal cancer radiation response.Results72 individual biomarkers, across 74 studies, were identified through review. On highest order classification, molecular biomarkers falling within the domains of response to stress, cellular metabolism and pathways inhibiting apoptosis were found to be the most influential in predicting radiosensitivity.ConclusionsHomogenising biomarker data from original articles using controlled GO terminology demonstrates that cellular mechanisms of response to radiotherapy in RC - in particular the metabolic response to radiotherapy - may hold promise in developing radiotherapeutic biomarkers with which to predict, and in the future modulate, radiation response.
Wafi A, Mirnezami R, 2018, Translational -omics: Future potential and current challenges in precision medicine, METHODS, Vol: 151, Pages: 3-11, ISSN: 1046-2023
Cookson NE, Mirnezami R, Ziprin P, 2015, Acute Cholangitis following Intraductal Migration of Surgical Clips 10 Years after Laparoscopic Cholecystectomy, CASE REPORTS IN GASTROINTESTINAL MEDICINE, Vol: 2015, ISSN: 2090-6528
Mirnezami R, Moran BJ, Harvey K, et al., 2014, Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal metastases, WORLD JOURNAL OF GASTROENTEROLOGY, Vol: 20, Pages: 14018-14032, ISSN: 1007-9327
Mirnezami R, Mehta AM, Chandrakumaran K, et al., 2014, Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy improves survival in patients with colorectal peritoneal metastases compared with systemic chemotherapy alone, BRITISH JOURNAL OF CANCER, Vol: 111, Pages: 1500-1508, ISSN: 0007-0920
Krell J, Frampton AE, Mirnezami R, et al., 2014, Growth Arrest-Specific Transcript 5 Associated snoRNA Levels Are Related to p53 Expression and DNA Damage in Colorectal Cancer, PLOS One, Vol: 9, ISSN: 1932-6203
Background: The growth arrest-specific transcript 5 gene (GAS5) encodes a long noncoding RNA (lncRNA) and hosts anumber of small nucleolar RNAs (snoRNAs) that have recently been implicated in multiple cellular processes and cancer.Here, we investigate the relationship between DNA damage, p53, and the GAS5 snoRNAs to gain further insight into thepotential role of this locus in cell survival and oncogenesis both in vivo and in vitro.Methods: We used quantitative techniques to analyse the effect of DNA damage on GAS5 snoRNA expression and to assessthe relationship between p53 and the GAS5 snoRNAs in cancer cell lines and in normal, pre-malignant, and malignanthuman colorectal tissue and used biological techniques to suggest potential roles for these snoRNAs in the DNA damageresponse.Results: GAS5-derived snoRNA expression was induced by DNA damage in a p53-dependent manner in colorectal cancercell lines and their levels were not affected by DICER. Furthermore, p53 levels strongly correlated with GAS5-derived snoRNAexpression in colorectal tissue.Conclusions: In aggregate, these data suggest that the GAS5-derived snoRNAs are under control of p53 and that they havean important role in mediating the p53 response to DNA damage, which may not relate to their function in the ribosome.We suggest that these snoRNAs are not processed by DICER to form smaller snoRNA-derived RNAs with microRNA (miRNA)-like functions, but their precise role requires further evaluation. Furthermore, since GAS5 host snoRNAs are often used asendogenous controls in qPCR quantifications we show that their use as housekeeping genes in DNA damage experimentscan lead to inaccurate results.
Mirnezami R, Jimenez B, Li JV, et al., 2014, Rapid Diagnosis and Staging of Colorectal Cancer via High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HR-MAS NMR) Spectroscopy of Intact Tissue Biopsies, Annals of Surgery, Vol: 259, Pages: 1138-1149, ISSN: 0003-4932
Objective: To develop novel metabolite-based models for diagnosis and staging in colorectal cancer (CRC) using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy.Background: Previous studies have demonstrated that cancer cells harbor unique metabolic characteristics relative to healthy counterparts. This study sought to characterize metabolic properties in CRC using HR-MAS NMR spectroscopy.Methods: Between November 2010 and January 2012, 44 consecutive patients with confirmed CRC were recruited to a prospective observational study. Fresh tissue samples were obtained from center of tumor and 5 cm from tumor margin from surgical resection specimens. Samples were run in duplicate where tissue volume permitted to compensate for anticipated sample heterogeneity. Samples were subjected to HR-MAS NMR spectroscopic profiling and acquired spectral data were imported into SIMCA and MATLAB statistical software packages for unsupervised and supervised multivariate analysis.Results: A total of 171 spectra were acquired (center of tumor, n = 88; 5 cm from tumor margin, n = 83). Cancer tissue contained significantly increased levels of lactate (P < 0.005), taurine (P < 0.005), and isoglutamine (P < 0.005) and decreased levels of lipids/triglycerides (P < 0.005) relative to healthy mucosa (R2Y = 0.94; Q2Y = 0.72; area under the curve, 0.98). Colon cancer samples (n = 49) contained higher levels of acetate (P < 0.005) and arginine (P < 0.005) and lower levels of lactate (P < 0.005) relative to rectal cancer samples (n = 39). In addition unique metabolic profiles were observed for tumors of differing T-stage.Conclusions: HR-MAS NMR profiling demonstrates cancer-specific metabolic signatures in CRC and reveals metabolic differences between colonic and rectal cancers. In addition, this approach reveals that tumor metabolism undergoes modification during local tumor advancement, offering potential in future staging and therapeu
Mirnezami R, Spagou K, Vorkas PA, et al., 2014, Chemical mapping of the colorectal cancer microenvironment via MALDI imaging mass spectrometry (MALDI-MSI) reveals novel cancer-associated field effects, Molecular Oncology, Vol: 8, Pages: 39-49, ISSN: 1574-7891
Matrix‐assisted laser desorption ionisation imaging mass spectrometry (MALDI‐MSI) is a rapidly advancing technique for intact tissue analysis that allows simultaneous localisation and quantification of biomolecules in different histological regions of interest. This approach can potentially offer novel insights into tumour microenvironmental (TME) biochemistry. In this study we employed MALDI‐MSI to evaluate fresh frozen sections of colorectal cancer (CRC) tissue and adjacent healthy mucosa obtained from 12 consenting patients undergoing surgery for confirmed CRC. Specifically, we sought to address three objectives: (1) To identify biochemical differences between different morphological regions within the CRC TME; (2) To characterise the biochemical differences between cancerous and healthy colorectal tissue using MALDI‐MSI; (3) To determine whether MALDI‐MSI profiling of tumour‐adjacent tissue can identify novel metabolic ‘field effects’ associated with cancer. Our results demonstrate that CRC tissue harbours characteristic phospholipid signatures compared with healthy tissue and additionally, different tissue regions within the CRC TME reveal distinct biochemical profiles. Furthermore we observed biochemical differences between tumour‐adjacent and tumour‐remote healthy mucosa. We have referred to this ‘field effect’, exhibited by the tumour locale, as cancer‐adjacent metaboplasia (CAM) and this finding builds on the established concept of field cancerisation.
Veselkov KA, Mirnezami R, Strittmatter N, et al., 2014, Chemo-informatic strategy for imaging mass spectrometry-based hyperspectral profiling of lipid signatures in colorectal cancer, Proceedings of the National Academy of Sciences of the United States of America, Vol: 111, Pages: 1216-1221, ISSN: 0027-8424
Mass spectrometry imaging (MSI) provides the opportunity toinvestigate tumor biology from an entirely novel biochemicalperspective and could lead to the identification of a new pool ofcancer biomarkers. Effective clinical translation of histology-drivenMSI in systems oncology requires precise colocalization of morphologicaland biochemical features as well as advanced methodsfor data treatment and interrogation. Currently proposed MSIworkflows are subject to several limitations, including nonoptimizedraw data preprocessing, imprecise image coregistration,and limited pattern recognition capabilities. Here we outline acomprehensive strategy for histology-driven MSI, using desorptionelectrospray ionization that covers (i) optimized data preprocessingfor improved information recovery; (ii) precise imagecoregistration; and (iii) efficient extraction of tissue-specific molecularion signatures for enhanced biochemical distinction of differenttissue types. The proposed workflow has been used to investigateregion-specific lipid signatures in colorectal cancer tissue. Uniquelipid patterns were observed using this approach according totissue type, and a tissue recognition system using multivariatemolecular ion patterns allowed highly accurate (>98%) identificationof pixels according to morphology (cancer, healthy mucosa,smooth muscle, and microvasculature). This strategy offers uniqueinsights into tumor microenvironmental biochemistry and shouldfacilitate compilation of a large-scale tissue morphology-specificMSI spectral database with which to pursue next-generation, fullyautomated histological approaches.
Mirnezami R, Veselkov K, Goldin RD, et al., 2013, Novel mass spectrometry based imaging for accurate characterisation of tumour microenvironmental metabolism in colorectal cancer, International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland (ASGBI), Publisher: WILEY-BLACKWELL, Pages: 3-3, ISSN: 0007-1323
Balog J, Sasi-Szabo L, Kinross J, et al., 2013, Intraoperative tissue identification using rapid evaporative ionization mass spectrometry, Science Translational Medicine, Vol: 5, Pages: 1-11, ISSN: 1946-6234
Rapid evaporative ionization mass spectrometry (REIMS) is an emerging technique that allows near–real-time characterization of human tissue in vivo by analysis of the aerosol (“smoke”) released during electrosurgical dissection. The coupling of REIMS technology with electrosurgery for tissue diagnostics is known as the intelligent knife (iKnife). This study aimed to validate the technique by applying it to the analysis of fresh human tissue samples ex vivo and to demonstrate the translation to real-time use in vivo in a surgical environment. A variety of tissue samples from 302 patients were analyzed in the laboratory, resulting in 1624 cancerous and 1309 noncancerous database entries. The technology was then transferred to the operating theater, where the device was coupled to existing electrosurgical equipment to collect data during a total of 81 resections. Mass spectrometric data were analyzed using multivariate statistical methods, including principal components analysis (PCA) and linear discriminant analysis (LDA), and a spectral identification algorithm using a similar approach was implemented. The REIMS approach differentiated accurately between distinct histological and histopathological tissue types, with malignant tissues yielding chemical characteristics specific to their histopathological subtypes. Tissue identification via intraoperative REIMS matched the postoperative histological diagnosis in 100% (all 81) of the cases studied. The mass spectra reflected lipidomic profiles that varied between distinct histological tumor types and also between primary and metastatic tumors. Thus, in addition to real-time diagnostic information, the spectra provided additional information on divergent tumor biochemistry that may have mechanistic importance in cancer.
Mirnezami R, Veselkov K, Strittmatter N, et al., 2013, Novel data processing and image co-registration algorithm for region-specific lipid profiling in colorectal cancer tissue using DESI imaging mass spectrometry, 49th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
Mirnezami R, Chang GJ, Das P, et al., 2013, Intraoperative radiotherapy in colorectal cancer: Systematic review and meta-analysis of techniques, long-term outcomes, and complications, SURGICAL ONCOLOGY-OXFORD, Vol: 22, Pages: 22-35, ISSN: 0960-7404
Jimenez B, Mirnezami R, Kinross J, et al., 2013, H-1 HR-MAS NMR Spectroscopy of Tumor-Induced Local Metabolic "Field-Effects" Enables Colorectal Cancer Staging and Prognostication, JOURNAL OF PROTEOME RESEARCH, Vol: 12, Pages: 959-968, ISSN: 1535-3893
Mirnezami A, Mirnezami R, Chandrakumaran K, et al., 2012, Reply to: Anastomotic Leak and Local Recurrence in Colorectal Cancer Reply, ANNALS OF SURGERY, Vol: 256, Pages: E34-E34, ISSN: 0003-4932
Mirnezami R, Kinross JM, Vorkas PA, et al., 2012, Implementation of Molecular Phenotyping Approaches in the Personalized Surgical Patient Journey, ANNALS OF SURGERY, Vol: 255, Pages: 881-889, ISSN: 0003-4932
Mirnezami R, Nicholson J, Darzi A, 2012, Preparing for Precision Medicine, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 366, Pages: 489-491, ISSN: 0028-4793
Mirnezami R, Kang C, Pai M, et al., 2011, Meta-analysis of survival outcomes following radiofrequency ablation (RFA) versus surgical resection (SR) for hepatocellular carcinoma (HCC), International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland, Publisher: WILEY-BLACKWELL, Pages: 9-9, ISSN: 0007-1323
Mirnezami A, Mirnezami R, Chandrakumaran K, et al., 2011, Increased Local Recurrence and Reduced Survival From Colorectal Cancer Following Anastomotic Leak Systematic Review and Meta-Analysis, ANNALS OF SURGERY, Vol: 253, Pages: 890-899, ISSN: 0003-4932
Mirnezami R, Mirnezami AH, Chandrakumaran K, et al., 2011, Short- and long-term outcomes after laparoscopic and open hepatic resection: systematic review and meta-analysis, HPB, Vol: 13, Pages: 295-308, ISSN: 1365-182X
Mirnezami AH, Mirnezami R, Venkatasubramaniam AK, et al., 2010, Robotic colorectal surgery: hype or new hope? A systematic review of robotics in colorectal surgery, COLORECTAL DISEASE, Vol: 12, Pages: 1084-1093, ISSN: 1462-8910
Mirnezami A, Mirnezami R, Sasapu K, et al., 2010, IMPACT OF ANASTAMOTIC LEAKAGE ON LONGTERM DISEASE RECURRENCE AND SURVIVAL FOLLOWING CURATIVE SURGERY FOR COLORECTAL CANCER, Annual Meeting of the American-Society-of-Colon-and-Rectal-Surgeons, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 645-645, ISSN: 0012-3706
Hamouda A, Forshaw M, Rohatgi A, et al., 2010, Presentation and Survival of Operable Esophageal Cancer in Patients 55 Years of Age and Below, WORLD JOURNAL OF SURGERY, Vol: 34, Pages: 744-749, ISSN: 0364-2313
Mirnezami R, Mirnezami A, Chandrakumaran K, et al., 2010, Oncological and survival outcomes following anastomotic leakage after colorectal cancer surgery: a meta-analysis, Electronic Poster of Distinction in Association-of-Surgeons-of-Great-Britain-and-Ireland-International-Surgical-Congress, Publisher: WILEY-BLACKWELL, Pages: 25-25, ISSN: 0007-1323
Mirnezami R, Rohatgi A, Sutcliffe RP, et al., 2010, Multivariate analysis of clinicopathological factors influencing survival following esophagectomy for cancer, INTERNATIONAL JOURNAL OF SURGERY, Vol: 8, Pages: 58-63, ISSN: 1743-9191
Mirnezami R, Chandrakumaran K, Mirnezami AH, et al., 2010, Short-term outcomes after laparoscopic versus open liver resection: results of a meta-analysis, Electronic Poster of Distinction in Association-of-Surgeons-of-Great-Britain-and-Ireland-International-Surgical-Congress, Publisher: WILEY-BLACKWELL, Pages: 137-138, ISSN: 0007-1323
Mirnezami R, Rohatgi A, Sutcliffe RP, et al., 2009, Transhiatal oesophagectomy: treatment of choice for high-grade dysplasia, EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, Vol: 36, Pages: 364-367, ISSN: 1010-7940
Mirnezami R, Sahai A, Symes A, et al., 2007, Day-case and short-stay surgery: the future for thyroidectomy?, INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Vol: 61, Pages: 1216-1222, ISSN: 1368-5031
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