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E Smyth

Publications and source records attributed to E Smyth.

At least 19 recordsLinked to original sources
PubMed2026

Antibody-drug conjugates in selected solid tumours: a position statement update based on findings from the third workshop held by the ETOP IBCSG Partners Foundation.

The European Thoracic Oncology Platform (ETOP) International Breast Cancer Study Group (IBCSG) Partners Foundation initiated a series of workshops for experts to review current evidence and offer recommendations to guide future antibody-drug conjugate (ADC) research. Here, we summarise key findings from the third workshop, which included experts in various solid tumours, basic/translational research scientists and pharmaceutical industry representatives. Recent positive phase III trial data have further incorporated ADCs into the standard of care [e.g. lung: sacituzumab tirumotecan; breast: trastuzumab deruxtecan (T-DXd), sacituzumab govitecan, datopotamab deruxtecan; muscle-invasive bladder cancer: enfortumab vedotin; ovarian cancer: mirvetuximab soravastine; cervical cancer: tisotumab vedotin]. Thus, research priorities must be tailored according to tumour type, potentially focussing initially on settings where ADCs could replace chemotherapy. Many phase III ADC trials have been initiated based on positive phase I data and although these trials are larger than those conducted historically, prespecified criteria (e.g. patient numbers and magnitude of efficacy) should be met to justify proceeding directly to phase III. Importantly, although several ADCs have been successfully developed without mandatory biomarker selection, biomarker-driven ADC development enables rational patient selection, as illustrated by multiple ADCs (e.g. T-DXd, mirvetuximab soravtansine and telisotuzumab vedotin). The identification, development and validation of predictive biomarkers are therefore essential, particularly given several critical nuances, including the algorithms used to assess biomarker status and the type of specimen analysed, all of which may be influenced by temporal and spatial heterogeneity. Additional ADC research priorities include the optimisation of ADC constructs to enhance efficacy/tolerability and the identification of reliable ADC targets, including work to elucidate attributes of already-identified targets. Finally, considering the vast amount of ADC-related data being generated, artificial intelligence could be leveraged to analyse combined datasets and generate composite biomarkers, including tumour histology, optimal target expression thresholds, molecular alterations and activated pathways affecting payload activity and target function, to accelerate research.

Humans↗
PubMed2005

Clinician-led surgical site infection surveillance of orthopaedic procedures: a UK multi-centre pilot study.

The UK Department of Health established the Healthcare-associated Infection (HAI) Surveillance Steering Group in 2000 to develop a strategy for implementing a national programme for HAI surveillance in National Health Service trusts. A subgroup of this committee examined the surveillance of surgical site infections following orthopaedic surgery. This group oversaw a pilot scheme that was set up in 12 hospitals around the UK to explore the feasibility of implementing a system of surveillance that engaged clinical staff in its operation, provided a process for continuous data collection and could be maintained as part of routine hospital operation over time. A minimum data set was established by the subgroup, and Centers for Disease Control and Prevention (CDC) definitions of infection were used. By March 2003, the surveillance had been undertaken continuously in 11 sites for one to two years, depending on the date of implementation. Only one hospital had ceased data collection. The information was collected mainly by clinical staff, with support and co-ordination usually provided by infection control teams. Data on more than 5400 procedures were available for analysis for four core procedures: arthroplasty of the hip and knee; hemi-arthroplasty of the hip; and internal fixation of trochanteric fractures of the femur. The data set permitted the calculation of risk-adjusted rates, allowing comparisons between hospitals and within a hospital over time. The methodology enhanced clinical ownership of the surveillance process, re-inforced infection control as the responsibility of all staff, and provided timely feedback and local data analysis. The use of CDC definitions permitted international comparisons of the data.

Adult↗
PubMed2005

A case of septic arthritis due to infection with Gemella morbillorum.

Gemella morbillorum is a facultatively anaerobic Gram-positive coccus which forms part of the normal flora of the oro-pharynx and the upper respiratory tract. It rarely causes human infection but has been described previously in cases of empyema and lung abscess, septic shock, endocarditis, meningitis, and osteomyelitis. We describe a case of septic arthritis due to G. morbillorum occurring in an otherwise healthy 42-year old man and review previous reports of infection in the literature.

Adult↗
PubMed2005

A case of multiple cerebral abscesses due to infection with Cladophialophora bantiana.

Cladophialophora bantiana is a highly neurotropic fungus which has been reported to cause a variety of infections in the immunocompromised and transplant populations. We describe a case of multiple cerebral abscesses caused by this dematiaceous fungus in a patient with probable Duncan's syndrome. The patient also had extensive extra-cerebral disease, which is unusual for infection with this organism. We discuss previously described cases of infection with Cladophialophora bantiana, and review the current and evolving treatment options.

Adult↗
PubMed2004

An after-hours clinical liaison blood culture service--is it worth it?

The impact of clinical liaison on therapy for positive after-hours blood cultures was evaluated. Of 223 positive blood cultures, no change in management occurred in 164 (73%) cases: 115 positive cultures were regarded as contaminants, and 49 patients were receiving appropriate therapy already. The results of microscopy or culture altered the antimicrobial management of 59 (27%) patients: therapy was altered on the basis of microscopy for 33 patients, and was altered for 26 patients when culture results were available. In total, 94 doses of inappropriate antibiotics were avoided. The main benefit of after-hours blood cultures was that laboratory results were available a day earlier, facilitating timely initiation of appropriate therapy and infection control procedures.

Anti-Bacterial Agents↗
PubMed2003

A twelve-year review of central nervous system bacterial abscesses; presentation and aetiology.

OBJECTIVES: To review and document the changing patterns in diagnosis, causes and treatment of bacterial infections of the central nervous system (CNS) in a national neurosurgical unit only in patients from whom a specimen was obtained for culture. METHODS: The case notes, radiological results and laboratory records of all 163 patients in our institution who underwent a neurosurgical procedure between 1988 and 2000 for a CNS abscess in a national center were reviewed retrospectively. Those patients from whom there were no operative specimens (i.e. neurosurgical intervention was not performed) and who were treated empirically were excluded, as were patients with mycobacterial infection. RESULTS: The mean age of the 163 patients was 35.2 years. Headache, pyrexia and an altered mental state were the commonest presentations. The frontal lobe was the commonest anatomical site (62 patients, 38%) and the majority of abscesses occurred following community infections such as sinusitis and mastoiditis; no primary source could be identified in 32 (20%) patients. Bacteria were isolated from 73% of patients and polymicrobial infections occurred in 29 (17.7%) patients. Anaerobes accounted for only 13.6% of isolates and methicillin-resistant Staphylococcus aureus (MRSA) was isolated on five occasions, all in the last five years of this review. Sixteen (9.8%) patients died prior to discharge or transfer back to the original referring hospital and 18 (11%) patients developed epilepsy. CONCLUSION: There was a relatively high incidence of polymicrobial infection but the number of specimens with anaerobes was small, which may be because of the use of empiric metronidazole before surgical intervention. Most infections were community-acquired and responded well to a combination of surgical drainage and antibiotic therapy. The emergence of MRSA in this group of patients is, however, worrying.

Adolescent↗
PubMed2002

Environmental regulation of biofilm formation in intensive care unit isolates of Staphylococcus epidermidis.

Staphylococcus epidermidis is a common cause of prosthetic device-related infection in the intensive care unit (ICU). The environmentally regulated ica operon encodes a polysaccharide adhesin which is a key virulence determinant in the development of S. epidermidis biofilms. To evaluate the capacity of ICU S. epidermidis isolates to form biofilm, we measured biofilm production by 18 isolates associated with device-related infection and 20 contaminating isolates that were not associated with clinically diagnosed infection. Biofilm assays were performed in brain-heart infusion (BHI) medium and in BHI supplemented with salt, ethanol or subinhibitory tetracycline, all of which have the potential to promote biofilm formation. Polymerase chain reaction (PCR) was used to screen for the presence of the ica genes. A significant proportion of S. epidermidis strains associated with device-related infections (89%) were found to contain the ica locus compared with 50% of contaminating isolates (P = 0.01). However only four of 26 (15.3%) of all ica-positive isolates were biofilm-positive when grown in BHI medium, indicating that no significant association existed between the presence of the ica locus and biofilm-forming capacity, under standard growth conditions. In contrast the number of ica-positive isolates that were biofilm-positive under stress-inducing growth conditions or in the presence of subinhibitory tetracycline increased significantly to 73% (P = 0.02). These findings suggest that the presence of the ica locus alone is not sufficient for biofilm formation and that regulation of biofilm formation under altered growth conditions, which may exist in the in vivo environment, also plays a possible role in the pathogenesis of biomaterial-related S. epidermidis infections.

Biofilms↗
PubMed2001

Solution structure of native proteins with irregular folds from Raman optical activity.

Raman optical activity (ROA) spectra have been measured for the proteins hen phosvitin, yeast invertase, bovine alpha-casein, soybean Bowman-Birk protease inhibitor, and rabbit Cd(7)-metallothionein, all of which have irregular folds in the native state. The results show that ROA is able to distinguish between two types of disorder. Specifically, invertase, alpha-casein, the Bowman-Birk inhibitor, and metallothionein appear to possess a "static" type of disorder similar to that in disordered states of poly(L-lysine) and poly(L-glutamic acid); whereas phosvitin appears to possess a more "dynamic" type of disorder similar to that in reduced (unfolded) lysozyme and ribonuclease A and also in molten globule protein states. In the delimiting cases, static disorder corresponds to that found in loops and turns within native proteins with well-defined tertiary folds that contain sequences of residues with fixed but nonrepetitive phi,psi angles; and dynamic disorder corresponds to that envisaged for the model random coil in which there is a distribution of Ramachandran phi,psi angles for each amino acid residue, giving rise to an ensemble of interconverting conformers. In both cases there is a propensity for the phi,psi angles to correspond to the alpha, beta and poly(L-proline) II (PPII) regions of the Ramachandran surface, as in native proteins with well-defined tertiary folds. Our results suggest that, with the exception of invertase and metallothionein, an important conformational element present in the polypeptide and protein states supporting the static type of disorder is that of the PPII helix. Long sequences of relatively unconstrained PPII helix, as in alpha-casein, may impart a plastic (rheomorphic) character to the structure.

Animals↗
PubMed2000

Interpretative reporting and selective antimicrobial susceptibility release in non-critical microbiology results.

The action taken in response to 169 positive sputum, urine and wound culture reports was examined. All reports included interpretative comments. Antimicrobial susceptibilities were released in 29 (17%). Therapy was significantly more likely to be started or altered in response to reports where susceptibilities were released (13 of 29, 45%) versus those without susceptibility release (31 of 140, 22%). Susceptibility release did not influence the appropriateness of antibiotic therapy. The clinical microbiology team was contacted for therapeutic advice in response to 32 (19%) reports. Of the remaining 137 reports, therapy was started or altered in response to 30 (22%) reports, but was considered appropriate in only seven (22%) of these.

Anti-Bacterial Agents↗
PubMed2000

The pathology of familial breast cancer: histological features of cancers in families not attributable to mutations in BRCA1 or BRCA2.

Breast cancers arising in carriers of mutations in the breast cancer susceptibility genes, BRCA1 and BRCA2, differ histologically from each other and from breast cancers unselected for a family history. However, a substantial proportion of families with multiple cases of breast cancer is not attributable to these two genes (non-BRCA1/2 families). We have now characterized the pathology of 82 breast cancers from non-BRCA1/2 families. Breast cancers in non-BRCA1/2 families were of lower grade (P = 0.0018), showed fewer mitoses (P < 0.0001), less nuclear pleomorphism (P = 0.0014), less lymphocytic infiltrate (P < 0.0001), a lesser extent of the tumor with a continuous pushing margin (P = 0.004), a lesser extent of the tumor composed of solid sheets of cells (P = 0.0047), less necrosis (P = 0.002), and wereparison with BRCA2 tumors, non-BRCA1/2 tumors were lower grade (P = 0.017) and exhibited less pleomorphism (P = 0.01) and more tubule formation (P = 0.05). In comparison with control breast cancers unselected for a family history of the disease, non-BRCA1/2 tumors were of significantly lower grade (P = 0.001), showed less pleomorphism (P = 0.0002), and had a lower mitotic count (P = 0.003). The results indicate that non-BRCA1/2 breast cancers differ histologically from both BRCA1 and BRCA2 breast cancers and are overall of lower grade. They also suggest that non-BRCA1/2 breast cancers differ from nonfamilial breast cancers, but these differences may be attributable to various types of bias.

BRCA2 Protein↗
PubMed2000

A novel presentation of cryptococcal infection in a renal allograft recipient.

The population of immunosuppressed patients is growing rapidly because of the HIV epidemic and the rapid expansion in transplant medicine. These patients may present to a variety of clinical specialties with seemingly innocuous infections. We present here the first Irish case of primary cryptococcal cellulitis. The patient was a 62-year old renal transplant recipient and was immunosuppressed with Cyclosporine, Azathioprine and Prednisolone. He presented with an apparent bacterial cellulitis on the dorsum of the hand that had failed to respond to a 3-week course of oral antibiotics. There was no clinical evidence of systemic infection. There was tissue necrosis present and the area was debrided surgically. Histological examination of debrided tissue revealed necrotic granulomata and budding yeast-like organisms. Cryptococcus neoformans was cultured from this specimen. The patient was treated with oral fluconazole 400 mg daily for 6 weeks with complete healing of the infected area and no evidence of recurrence after 12 months of follow up. This case emphasises the need for a high index of suspicion for atypical infection in the immunocompromised patient.

Antifungal Agents↗
PubMed1999

Molecular pathology of breast cancer and its impact on clinical practice.

Molecular studies in breast cancer are in their infancy but infants mature very quickly nowadays. The impact of new technologies on medical practice is already becoming evident and will transform the entire scene within a generation. The most rapidly moving part of the field at present is familial breast cancer. Molecular data are available for only a minority of affected families today and this is reflected in a great deal of imprecision in selection of family members for special surveillance and in decisions about management. Nevertheless, it is important to be systematic in setting up and auditing services for breast cancer families so that these can evolve effectively in parallel with developments in molecular technology. Our limited experience of these services so far does at least suggest they are doing more good than harm!

Breast Neoplasms↗
PubMed1999

The information superhijack.

Infection control teams are not alone in their need to manipulate data. How best can such manipulation be achieved and what tools are available to turn information into knowledge. The workshop included discussion and demonstration of some methods currently being used by infection control teams. While the workshop did not aim to produce all the answers, participants were able to question, discuss and learn new ways that they might take their own practice in the future.

Cross Infection↗