47 results on '"G. Meachery"'
Search Results
2. Assessing coronavirus disease 2019 (COVID-19) transmission to healthcare personnel: The global ACT-HCP case-control study
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G. Meachery, Sara Tomassetti, Robert J. Lentz, Sarabon Tahura, Fabien Maldonado, Brandon P. Cohen, Rosa Cordovilla, Henri G. Colt, Piero Candoli, Heidi Chen, Bryan D. Harris, Thomas R. Talbot, and Spasoje Popevic
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Microbiology (medical) ,Adult ,Male ,Infectious Disease Transmission, Patient-to-Professional ,Epidemiology ,Infectious Disease Transmission ,Lower risk ,Logistic regression ,Global Health ,Medical and Health Sciences ,01 natural sciences ,Patient-to-Professional ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Intensive care ,Environmental health ,Occupational Exposure ,Health care ,Infection control ,Medicine ,Humans ,030212 general & internal medicine ,0101 mathematics ,Respiratory Protective Devices ,Personal protective equipment ,Personal Protective Equipment ,Aged ,business.industry ,Incidence (epidemiology) ,010102 general mathematics ,COVID-19 ,Odds ratio ,Middle Aged ,Infectious Diseases ,Logistic Models ,Case-Control Studies ,Original Article ,Female ,business - Abstract
Objective:To characterize associations between exposures within and outside the medical workplace with healthcare personnel (HCP) SARS-CoV-2 infection, including the effect of various forms of respiratory protection.Design:Case–control study.Setting:We collected data from international participants via an online survey.Participants:In total, 1,130 HCP (244 cases with laboratory-confirmed COVID-19, and 886 controls healthy throughout the pandemic) from 67 countries not meeting prespecified exclusion (ie, healthy but not working, missing workplace exposure data, COVID symptoms without lab confirmation) were included in this study.Methods:Respondents were queried regarding workplace exposures, respiratory protection, and extra-occupational activities. Odds ratios for HCP infection were calculated using multivariable logistic regression and sensitivity analyses controlling for confounders and known biases.Results:HCP infection was associated with non–aerosol-generating contact with COVID-19 patients (adjusted OR, 1.4; 95% CI, 1.04–1.9; P = .03) and extra-occupational exposures including gatherings of ≥10 people, patronizing restaurants or bars, and public transportation (adjusted OR range, 3.1–16.2). Respirator use during aerosol-generating procedures (AGPs) was associated with lower odds of HCP infection (adjusted OR, 0.4; 95% CI, 0.2–0.8, P = .005), as was exposure to intensive care and dedicated COVID units, negative pressure rooms, and personal protective equipment (PPE) observers (adjusted OR range, 0.4–0.7).Conclusions:COVID-19 transmission to HCP was associated with medical exposures currently considered lower-risk and multiple extra-occupational exposures, and exposures associated with proper use of appropriate PPE were protective. Closer scrutiny of infection control measures surrounding healthcare activities and medical settings considered lower risk, and continued awareness of the risks of public congregation, may reduce the incidence of HCP infection.
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- 2020
3. Recovering the lung transplant service after COVID-19 - experience at the Freeman Hospital, Newcastle
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James Lordan, G. Meachery, Falak Umair, Muhammad Waseem Athar, Andrew J. Fisher, and Arun Nair
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Service (business) ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Lung ,Coronavirus disease 2019 (COVID-19) ,business.industry ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,medicine.medical_treatment ,COVID-19 ,General Medicine ,030204 cardiovascular system & hematology ,Organ transplantation ,Hospitals ,03 medical and health sciences ,surgical procedures, operative ,0302 clinical medicine ,medicine.anatomical_structure ,Emergency medicine ,Medicine ,Lung transplantation ,Humans ,030212 general & internal medicine ,business ,Lung Transplantation - Abstract
COVID-19 caused a significant impact on organ transplantation. In the UK, during the peak months the number of deceased donors and transplants fell by 66% and 68% respectively compared with last year.[1][1] The lung transplant service at the Freeman Hospital, Newcastle covers a wide geographical
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- 2021
4. P077 Clinical factors affecting timing of referral for lung transplantation for people with cystic fibrosis: a national comparison of opinions between adult cystic fibrosis and transplant centres
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K. Bateman, J. Duckers, F P Edenborough, Anna Reed, K. Santhanakrishnan, J. Myers, S. Range, William G Flight, Kavita Dave, L. Baker, T. Daniels, Angela McGowan, H. Rogers, R L Thompson, N.J. Simmonds, Helen L. Barr, Daniel Peckham, Stephen Bourke, R. Thomas, Caroline Elston, V. Gerovasili, G. Meachery, S. Caskey, M.C. Pasteur, D. Derry, Edward F. Nash, F. Frost, M. Carby, U. Hill, A. Brennan, and D. Thomas
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Pulmonary and Respiratory Medicine ,Pediatrics ,medicine.medical_specialty ,Referral ,business.industry ,medicine.medical_treatment ,Pediatrics, Perinatology and Child Health ,medicine ,Lung transplantation ,medicine.disease ,business ,Cystic fibrosis - Published
- 2021
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5. Diagnosis and Predicted Outcomes of Patients with Cystic Fibrosis Related Liver Disease Considered for Lung Transplantation
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Stephen Clark, M. Hudson, E. Khoshbin, J.H. Dark, and G. Meachery
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Pulmonary and Respiratory Medicine ,Transplantation ,medicine.medical_specialty ,Lung ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,medicine.disease ,Cystic fibrosis ,Gastroenterology ,Liver disease ,medicine.anatomical_structure ,Internal medicine ,Biopsy ,medicine ,Portal hypertension ,Anxiety ,Lung transplantation ,Surgery ,Abnormality ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Purpose Anxiety associated with poor post operative outcomes has led to patients with Cystic Fibrosis Related Liver Disease (CFRLD) being denied a chance of lung transplant for fear of developing post-operative progressive hepatic impairment. Methods We studied a total of 238 transplanted patients. Patients were divided into two groups CFRLD and Non-CFRLD based on our new criterion. Groups were compared first to assess validity of the diagnosis and then survival outcomes. A predictor of hepatic injury was devised by modifying the APRI (Aspartate aminotransferase-to-Platelet Ratio Index) scores to diagnose CFRLD and predict severity of liver disease. Results The new diagnostic criteria for differentiating CFRLD from Non CFRLD was effective. This was supported by significant difference in serum Bilirubin from 6.1 to 9.4 micromole / L at 90 days post transplant (p = 0.0001). There was no significant difference in the survival between the two groups at short, medium or long term demonstrated by the Kaplan-Meier plot with survival of 85%, 73%, 47%, 18.6% and 4.7% at one, two, five, ten and 15 year respectively. A modified APRI score of greater than 0.2 had a sensitivity of 43.0% but a specificity of 82.5 % for predicting CFRLD and 46.5% sensitivity but 100% specificity in diagnosing an ultrasound/biopsy proven hepatic abnormality associated with CFRLD. Conclusion Patients with CFRLD and portal hypertension but with preserved hepatocellular function have a similar outcome to patients without CFRLD. Modified APRI sore is a highly specific non-invasive tool for diagnosis of CFRLD.
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- 2021
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6. Observational Study of Methotrexate in the Treatment of Bronchiolitis Obliterans Syndrome
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Logan Thirugnanasothy, Paul A. Corris, James Lordan, Andrew J. Fisher, Sasiharan Sithamparanathan, Gareth Parry, G. Meachery, and Katie Morley
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Nausea ,medicine.medical_treatment ,Bronchiolitis obliterans ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Forced Expiratory Volume ,Internal medicine ,medicine ,Humans ,Lung transplantation ,030212 general & internal medicine ,Bronchiolitis Obliterans ,Lung ,Retrospective Studies ,Immunosuppression Therapy ,Transplantation ,business.industry ,Immunosuppression ,Leukopenia ,Middle Aged ,medicine.disease ,Respiratory Function Tests ,Discontinuation ,Surgery ,Methotrexate ,Treatment Outcome ,medicine.anatomical_structure ,030228 respiratory system ,Tolerability ,Female ,medicine.symptom ,business ,Immunosuppressive Agents ,Lung Transplantation ,medicine.drug - Abstract
Background Methotrexate (MTX) is potential change in immunosuppression after lung transplantation that may help to slow down the decline in lung function in bronchiolitis obliterans syndrome (BOS). Methods We sought to analyze the safety and efficacy of MTX in patients with BOS, by retrospective case review. Results Thirty lung allograft patients were treated with MTX for BOS after one bilateral lower lobe, nine single, 16 bilateral, and four heart-lung transplants. Twenty-one patients had MTX treatment for a minimum of 6 months, and their serial lung function was analyzed for efficacy. In these patients, there was a significant overall increase in mean forced expiratory volume in 1 second (FEV 1 ) of 149 mL ( P 1 of 117 mL ( P 1 of 60 mL ( P = .19) observed in 18 patients who had MTX for this time period. The rate of decline in FEV 1 before MTX was 118.5 mL/month and at 3 months after MTX increased to 49.5 mL/months ( P 1 . Nine patients had been treated with MTX for less than 6 months; two died within 6 months of starting MTX, five tolerated the drug poorly with nausea and tiredness, and one developed leucopenia. One patient requested discontinuation of the medication after failing to halt the rapid progressive decline in lung function after 1 month. Conclusions Methotrexate therapy provides a potential therapeutic strategy in managing the progressive decline in lung function observed in BOS. This is hampered by the observation of poor tolerability and side effects.
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- 2016
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7. Observational study of lung transplant recipients surviving 20 years
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Sasiharan Sithamparanathan, John H. Dark, James Lordan, Gareth Parry, G. Meachery, Paul A. Corris, Kate Gould, Logan Thirugnanasothy, Andrew J. Fisher, Stephen Clark, and Asif Hasan
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Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Cystic Fibrosis ,medicine.medical_treatment ,Bronchiolitis obliterans ,030230 surgery ,Cystic fibrosis ,03 medical and health sciences ,0302 clinical medicine ,Forced Expiratory Volume ,Diabetes mellitus ,Internal medicine ,Prevalence ,Humans ,Medicine ,Lung transplantation ,Renal replacement therapy ,Bronchiolitis Obliterans ,Immunosuppression Therapy ,COPD ,business.industry ,Immunosuppression ,medicine.disease ,Lymphoproliferative Disorders ,Transplant Recipients ,humanities ,Surgery ,Survival Rate ,Transplantation ,030228 respiratory system ,Female ,business ,Lung Transplantation - Abstract
Background Lung transplant recipients have reduced long-term survival compared with other solid organ recipients. There is a lack of published data on the characteristics of very long term survivors. Methods We describe the demographics, clinical history and post-procedure function of all lung transplant recipients who have survived greater than 20 years at our centre. Results At the time of analysis there were 21 (16.4%) of 128 patients who survived over 20 years. The mean age at transplantation was 31.8 ± 9.9 years. Five of 21 had undergone single-lung, eight double-lung and eight heart-lung transplant procedures. At the last evaluation, mean percentage predicted FEV1 in recipients of single and double lung were 51.3% and 57.9% respectively. By 20 years, 19 (90.5%) patients had developed bronchiolitis obliterans syndrome (BOS) with three (14%) BOS 1, six (29%) BOS 2 and 10 (48%) BOS 3 and two (9.5%) free from BOS. The median time to onset of BOS was 9.7 years (range 1.6–17.9). Of eight patients (38%) who required renal replacement, four (19%) had successfully undergone renal transplantation and four (19%) were on haemodialysis. Only one patient (5%) had symptomatic osteoporosis. Nineteen patients (90%) were treated for hypertension. Five patients (24%) had diabetes, all with an underlying diagnosis of cystic fibrosis and four of them developing diabetes post operatively. Conclusions In our experience, 20-year survivors of lung transplantation had a delayed onset of BOS and morbidities due to immunosuppression that can be appropriately managed leading to long-term survival.
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- 2016
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8. Long-term effect of azithromycin in bronchiolitis obliterans syndrome
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James L. Lordan, G. Meachery, C.Tji-Joong Gan, Chris Ward, Andrew J. Fisher, and Paul A. Corris
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Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Bronchiolitis obliterans ,Azithromycin ,030230 surgery ,Placebo group ,Gastroenterology ,THERAPY ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Randomized controlled trial ,law ,Forced Expiratory Volume ,Internal medicine ,Post-hoc analysis ,Humans ,Medicine ,Lung transplantation ,Term effect ,Bronchiolitis Obliterans ,Lung ,business.industry ,Syndrome ,Middle Aged ,RANDOMIZED CONTROLLED-TRIAL ,medicine.disease ,humanities ,Survival Rate ,Treatment Outcome ,medicine.anatomical_structure ,030228 respiratory system ,Disease Progression ,SURVIVAL ,Female ,business ,LUNG ,Lung Transplantation ,medicine.drug - Abstract
IntroductionAzithromycin stabilises and improves lung function forced expiratory volume in one second (FEV1) in lung transplantation patients with bronchiolitis obliterans syndrome (BOS). A post hoc analysis was performed to assess the long-term effect of azithromycin on FEV1, BOS progression and survival .MethodsEligible patients recruited for the initial randomised placebo-controlled trial received open-label azithromycin after 3 months and were followed up until 6 years after inclusion (n=45) to assess FEV1, BOS free progression and overall survival.ResultsFEV1 in the placebo group improved after open-label azithromycin and was comparable with the treatment group by 6 months. FEV1 decreased after 1 and 5 years and was not different between groups. Patients (n=18) with rapid progression of BOS underwent total lymphoid irradiation (TLI). Progression-free survival (log-rank test p=0.40) and overall survival (log-rank test p=0.28) were comparable. Survival of patients with early BOS was similar to late-onset BOS (log-rank test p=0.74).DiscussionLong-term treatment with azithromycin slows down the progression of BOS, although the effect of TLI may affect the observed attenuation of FEV1 decline. BOS progression and long-term survival were not affected by randomisation to the placebo group, given the early cross-over to azithromycin and possibly due to TLI in case of further progression. Performing randomised placebo-controlled trials in lung transplantation patients with BOS with a blinded trial duration is feasible, effective and safe.
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- 2019
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9. Outcomes of lung transplantation in adults with bronchiectasis
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Stephen Clark, John H. Dark, G. Meachery, James L. Lordan, Gareth Parry, F. Kate Gould, Andrew J. Fisher, Syba Susan Sunny, Katy L.M. Hester, Anthony De Soyza, Paul A. Corris, and Jodie Birch
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Pulmonary and Respiratory Medicine ,Adult ,Male ,medicine.medical_specialty ,Time Factors ,Databases, Factual ,medicine.medical_treatment ,Sepsis ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Postoperative Complications ,Pseudomonas infection ,Internal medicine ,Pseudomonas ,Forced Expiratory Volume ,medicine ,Lung transplantation ,Humans ,Pseudomonas Infections ,030212 general & internal medicine ,Lung ,Survival analysis ,Retrospective Studies ,lcsh:RC705-779 ,Transplantation ,Bronchiectasis ,business.industry ,Retrospective cohort study ,lcsh:Diseases of the respiratory system ,A300 ,Middle Aged ,medicine.disease ,Survival Analysis ,medicine.anatomical_structure ,surgical procedures, operative ,030228 respiratory system ,Female ,business ,Research Article ,Lung Transplantation - Abstract
BACKGROUND: Lung transplantation is a well-established treatment for end-stage non-cystic fibrosis bronchiectasis (BR), though information regarding outcomes of transplantation remains limited. Our results of lung transplantation for Br are reported here.\ud \ud METHODS: A retrospective review of case notes and transplantation databases was conducted for patients that had underwent lung transplantation for bronchiectasis at the Freeman Hospital between 1990 and 2013.\ud \ud RESULTS: Fourty two BR patients underwent lung transplantation, the majority (39) having bilateral sequential lung transplantation. Mean age at transplantation was 47.1 years. Pre-transplantation osteoporosis was a significant non-pulmonary morbidity (48%). Polymicrobial infection was common, with Pseudomonas aeruginosa infection frequently but not universally observed (67%). Forced expiratory volume in 1 second (% predicted) improved from a pre-transplantation mean of 0.71 L (22% predicted) to 2.56 L (79 % predicted) at 1-year post-transplantation. Our survival results were 74% at 1 year, 64% at 3 years, 61% at 5 years and 48% at 10 years. Sepsis was a common cause of early post-transplantation deaths.\ud \ud CONCLUSIONS: Lung transplantation for end-stage BR is a useful therapeutic option, with good survival and lung function outcomes. Survival values were similar to other bilateral lung transplants at our centre. Pre-transplantation Pseudomonas infection is common.
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- 2018
10. Susceptibility Testing of Exophiala dermatitidis to Inform Peri-Operative Prophylaxis at Time of Lung Transplantation
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A. Hague, J. Samuel, Kate Gould, S. Peart, Audrey Perry, G. Meachery, Andrew J. Fisher, S. Mattu, and A. Robb
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Pulmonary and Respiratory Medicine ,Voriconazole ,Transplantation ,Posaconazole ,biology ,business.industry ,Itraconazole ,biology.organism_classification ,Microbiology ,chemistry.chemical_compound ,chemistry ,Amphotericin B ,medicine ,Sputum ,Surgery ,Caspofungin ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Exophiala dermatitidis ,Fluconazole ,medicine.drug - Abstract
Purpose Exophiala dermatitidis is a black fungus that frequently colonises the lungs of people with cystic fibrosis (CF). Mucoid and non-mucoid variants can be detected from the same sputum for some patients, but their role in chronic CF lung disease is not fully understood and attempts at early eradication are not routinely performed. Invasive infections with this species are rare; however in 2014 we reported our first case of fatal, invasive infection with a highly mucoid strain of E. dermatitidis in a 34 year old post lung transplant patient with CF. This prompted us to include peri-operative antifungal prophylaxis for all patients colonised with this species. To inform the choice of optimal antifungal, we performed susceptibility testing of 38 isolates from 34 patients including lung transplant patients. The ability of these isolates to produce biofilm was also investigated. Methods The minimum inhibitory concentration (MIC) of 8 antifungal agents was measured using a commercial broth microdilution assay. Biofilm formation was assessed using a standard in vitro assay using staining with crystal violet. Results Using breakpoints for Candida albicans, all isolates were susceptible to voriconazole and amphotericin B with most isolates also susceptible to itraconazole (89% of isolates) and posaconazole (71% of isolates). In contrast, all isolates were non-susceptible to caspofungin and most isolates (92%) non-susceptible to fluconazole. All strains were inhibited by ketoconazole at ≤0.25 mg/ L whereas MICs of 5-fluorocytosine ranged from 1->64 mg/ L. 31 of 38 isolates were biofilm producers including 4 isolates that were classified as strong biofilm producers. We did not find a correlation between mucoid phenotype and biofilm production. Conclusion E. dermatitidis is commonly found to colonise the lungs of patients with CF, typically produces biofilm, and may rarely produce serious infection post transplantation. We demonstrate in vitro susceptibility to voriconazole and amphotericin B. For patients colonised with this species, we now elect to include voriconazole as part of the peri-operative prophylactic regimen.
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- 2019
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11. Single- and Bilateral Lung Transplantation: Indications, Contraindications, Evaluation, and Requirements for Patients to Be Considered Eligible
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Paul A. Corris and G. Meachery
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Interstitial lung disease ,Bilateral lung transplantation ,respiratory system ,medicine.disease ,Clinical Practice ,Transplantation ,Idiopathic pulmonary fibrosis ,Lung disease ,Expert opinion ,medicine ,Lung transplantation ,Intensive care medicine ,business - Abstract
Single- and double-lung transplantation epitomize the final therapeutic options available to selected patients with advanced, end-stage lung disease refractory to all methods of available medical management. The lack of evidence supporting effective lung transplant practices is widely acknowledged, necessitating the need for expert opinion practice guidelines. In this chapter we present the key recommendations for consideration when referring and listing an individual for lung transplantation. We critique seminal papers that have revised our selection process for single- and bilateral lung transplant recipients and outline the indications and contraindications unique to different lung pathologies. We define our current clinical practice based on the best available international expert opinions and review future developments of treatments and novel approaches to deal with the continued lack of suitable donor organs.
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- 2018
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12. A randomised controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation
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GE Johnson, T Small, Andrew J. Fisher, Paul A. Corris, G. Meachery, Victoria Ryan, Chris Ward, and James Lordan
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Bronchiolitis obliterans ,Placebo ,Azithromycin ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Lung transplantation ,030212 general & internal medicine ,Adverse effect ,Intensive care medicine ,Intention-to-treat analysis ,business.industry ,medicine.disease ,Surgery ,3. Good health ,Transplantation ,030228 respiratory system ,business ,medicine.drug ,Lung Transplantation - Abstract
Background We conducted a placebo-controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation. Methods We compared azithromycin (250 mg alternate days, 12 weeks) with placebo. Primary outcome was FEV1 change at 12 weeks. Results 48 patients were randomised; (25 azithromycin, 23 placebo). It was established, post randomisation that two did not have BOS. 46 patients were analysed as intention to treat (ITT) with 33 ‘Completers’. ITT analysis included placebo patients treated with open-label azithromycin after study withdrawal. Outcome The ITT analysis (n=46, 177 observations) estimated mean difference in FEV1 between treatments (azithromycin minus placebo) was 0.035 L, with a 95% CI of −0.112 L to 0.182 L (p=0.6). Five withdrawals, who were identified at the end of the study as having been randomised to placebo (four with rapid loss in FEV1, one withdrawn consent) had received rescue open-label azithromycin, with improvement in subsequent FEV1 at 12 weeks. Study Completers showed an estimated mean difference in FEV1 between treatment groups (azithromycin minus placebo) of 0.278 L, with 95% CI for the mean difference: 0.170 L to 0.386 L (p=
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- 2015
13. Pregnancy after lung and heart-lung transplantation
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Paul A. Corris, G. Meachery, Mitesh V. Thakrar, Katie Morley, Gareth Parry, Andrew J. Fisher, and James Lordan
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Adult ,Pulmonary and Respiratory Medicine ,Spirometry ,Vital capacity ,medicine.medical_specialty ,Pediatrics ,Heart-Lung Transplantation ,medicine.medical_treatment ,Calcineurin Inhibitors ,Renal function ,Kidney Function Tests ,Preeclampsia ,Young Adult ,Pregnancy ,Forced Expiratory Volume ,medicine ,Humans ,Lung transplantation ,Retrospective Studies ,Transplantation ,medicine.diagnostic_test ,business.industry ,Pregnancy Outcome ,Immunosuppression ,medicine.disease ,Surgery ,Pregnancy Complications ,Creatinine ,Female ,Cardiology and Cardiovascular Medicine ,business ,Immunosuppressive Agents - Abstract
Background Advances in lung transplantation have enabled women to successfully undertake pregnancies. This study explored outcomes in this group, including changes in lung function, kidney function, and calcineurin inhibitor (CNI) levels. Methods A retrospective review identified 19 transplant recipients who had ever become pregnant at our center, and manual reviews of their medical records were completed for 14. Results of spirometry, serum creatinine, CNI doses and trough levels, and comorbidities were collected. Results Eight births occurred (42% success rate). Six patients have since died, with pregnancy contributing to 1 death. Five pregnancies were unplanned, with only 1 resulting in birth. Six pregnancies ended with spontaneous termination, and 2 were terminated for medical reasons. Mean age was 31.4 years (range, 22–39 years), and mean time from transplant was 76.2 months (range, 26–139 months). Complications included preeclampsia in 2, diabetes of pregnancy in 1, and abnormal liver enzymes in 1. Within 6 months of delivery, there were 2 cases of pneumonia, 2 cases of obliterative bronchiolitis, 1 case of tuberculosis, and 1 case of mild acute rejection. Forced expiratory volume in 1 second was stable at 3 (–1.5%; p = 0.55) and 12 months (1.4%; p = 0.84) after pregnancy. Mean change in Forced expiratory volume in 1 second during full-term pregnancies was –2.4% ( p = 0.29), and the mean change in forced vital capacity was –0.8% ( p = 0.55). In the first trimester, 83% of patients had a fall in creatinine, and a universal fall in CNI trough levels was seen. Conclusions In carefully selected patients, planned pregnancy after lung transplant can be successful. Complications are common, and close monitoring of immunosuppression and renal function is needed.
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- 2014
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14. An association of particulate air pollution and traffic exposure with mortality after lung transplantation in Europe
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Bart Luijk, Christian Benden, Ellen Winckelmans, Danielle Vienneau, Nikolaus Kneidinger, Walter Klepetko, Andrew J. Fisher, Erik A M Verschuuren, Claus Neurohr, Hannelore Bellon, Geert Verleden, Barbara Hoffmann, Jens Gottlieb, Robin Vos, Esmée M. Bijnens, Gregor Warnecke, Johanna M. Kwakkel-van Erp, Tim S. Nawrot, Martin Iversen, Hans Henrik Schultz, Benoit Nemery, G. Meachery, Elly Vandermeulen, Paul A. Corris, James Lordan, Antonio Roman, Gerard Hoek, Markus Kamler, Wim van der Bij, David Ruttens, Peter Jaksch, Davide Piloni, Gerhard Weinreich, Urte Sommerwerck, Bart M. Vanaudenaerde, Federica Meloni, Stijn E. Verleden, Are Martin Holm, Cristina Berastegui, Monica Morosini, Susana Gómez-Ollés, Kees de Hoogh, Erik Jan D Oudijk, RUTTENS, David, Verleden, Stijn E., BIJNENS, Esmee, WINCKELMANS, Ellen, Gottlieb, Jens, Warnecke, Gregor, Meloni, Federica, Morosini, Monica, Van Der Bij, Wim, Verschuuren, Erik A., Sommerwerck, Urte, Weinreich, Gerhard, Kamler, Markus, Roman, Antonio, Gomez-Olles, Susana, Berastegui, Cristina, Benden, Christian, Holm, AreMartin, Iversen, Martin, Schultz, Hans Henrik, Luijk, Bart, Oudijk, Erik-Jan, Erp, Johanna M. Kwakkel-van, Jaksch, Peter, Klepetko, Walter, Kneidinger, Nikolaus, Neurohr, Claus, Corris, Paul, Fisher, Andrew J., Lordan, James, Meachery, Gerard, Piloni, Davide, Vandermeulen, Elly, Bellon, Hannelore, Hoffmann, Barbara, Vienneau, Danielle, Hoek, Gerard, de Hoogh, Kees, Nemery, Benoit, Verleden, Geert M., Vos, Robin, NAWROT, Tim, Vanaudenaerde, Bart M., and Groningen Institute for Organ Transplantation (GIOT)
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Medizin ,AZITHROMYCIN ,Air pollution ,030204 cardiovascular system & hematology ,PLACEBO-CONTROLLED TRIAL ,NO2 ,medicine.disease_cause ,DOUBLE-BLIND ,03 medical and health sciences ,0302 clinical medicine ,USE REGRESSION-MODELS ,Environmental health ,medicine ,Lung transplantation ,Proportional hazards model ,business.industry ,BRONCHIOLITIS OBLITERANS SYNDROME ,Hazard ratio ,Confounding ,RANDOMIZED CONTROLLED-TRIAL ,Particulates ,PREVENTION ,Surgery ,ALLOGRAFT DYSFUNCTION ,EXACERBATIONS ,030228 respiratory system ,Cohort ,Human medicine ,business ,Cohort study - Abstract
Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies.13 lung transplant centres in 10 European countries created a cohort of 5707 patients. For each patient, we quantified residential particulate matter with aerodynamic diameter ≤10 µm (PM10) by land use regression models, and the traffic exposure by quantifying total road length within buffer zones around the home addresses of patients and distance to a major road or freeway.After correction for macrolide use, we found associations between air pollution variables and CLAD/mortality. Given the important interaction with macrolides, we stratified according to macrolide use. No associations were observed in 2151 patients taking macrolides. However, in 3556 patients not taking macrolides, mortality was associated with PM10 (hazard ratio 1.081, 95% CI 1.000–1.167); similarly, CLAD and mortality were associated with road lengths in buffers of 200–1000 and 100–500 m, respectively (hazard ratio 1.085– 1.130). Sensitivity analyses for various possible confounders confirmed the robustness of these associations.Long-term residential air pollution and traffic exposure were associated with CLAD and survival after lung transplantation, but only in patients not taking macrolides.
- Published
- 2017
15. Lung transplantation for patients with cystic fibrosis and Burkholderia cepacia complex infection: A single-center experience
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Stephen Clark, Anthony De Soyza, John H. Dark, A. Nicholson, K. Tocewicz, James Lordan, Stephan Schueler, Thasee Pillay, Gareth Parry, F. Kate Gould, Katy L.M. Hester, Andrew J. Fisher, Paul A. Corris, and G. Meachery
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Cystic Fibrosis ,Burkholderia cenocepacia ,medicine.medical_treatment ,Bronchiolitis obliterans ,Cystic fibrosis ,Cohort Studies ,Sepsis ,Species Specificity ,Cause of Death ,Internal medicine ,medicine ,Humans ,Lung transplantation ,Survival rate ,Retrospective Studies ,Transplantation ,integumentary system ,biology ,business.industry ,Burkholderia cepacia complex ,Respiratory disease ,Burkholderia Infections ,biology.organism_classification ,medicine.disease ,Anti-Bacterial Agents ,Survival Rate ,Treatment Outcome ,Immunology ,Surgery ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies ,Lung Transplantation - Abstract
Background Pre-operative infection with organisms from the Burkholderia cepacia complex (BCC), particularly B cenocepacia , has been linked with a poorer prognosis after transplantation compared to patients with cystic fibrosis (CF) without this infection. Therefore, many transplant centers do not list these patients for transplantation. Methods We report the early and long-term results of a cohort of lung transplant recipients with CF and pre-operative BCC infection. Patients with pre-transplantation BCC infection were identified by case-note review. BCC species status was assigned by polymerase chain reaction (PCR)-based techniques. Survival rates were compared to recipients with CF without BCC infection. Survival rates in BCC subgroups were also compared, and then further analyzed pre- and post-2001, when a new immunosuppressive and antibiotic regime was introduced for such patients. Results Two hundred sixteen patients with CF underwent lung transplantation and 22 had confirmed pre-operative BCC infection, with 12 of these being B cenocepacia. Nine B cenocepacia –infected recipients died within the first year, and in 8 BCC sepsis was considered to be the cause of death. Despite instituting a tailored peri-operative immunosuppressive and microbiologic care approach for such patients, post-transplantation BCC septic deaths occurred frequently in those with pre-transplantation B cenocepacia infection. In contrast, recipients infected with other BCC species had significantly better outcomes, with post-transplantation survival comparable to other recipients with CF. Conclusions Mortality in patients with B cenocepacia infection was unacceptably high and has led to our center no longer accepting patients with this condition onto the lung transplant waiting list. Long-term survival in the non– B cenocepacia BCC group was excellent, without high rates of acute rejection or bronchiolitis obliterans syndrome (BOS) longer term, and these patients continue to be considered for lung transplantation.
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- 2010
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16. Size Matters in Single Lung Transplantation for Pulmonary Fibrosis!
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Gareth Parry, Andrew J. Fisher, K.L. Freystaetter, J.H. Dark, G. Meachery, O. Senbaklavaci, and James Lordan
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Pulmonary and Respiratory Medicine ,Transplantation ,Pathology ,medicine.medical_specialty ,business.industry ,Pulmonary fibrosis ,Medicine ,Surgery ,Single Lung Transplantation ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease - Published
- 2018
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17. The impact of long-term air pollution and traffic on outcome after lung transplantation in Europe
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Walter Klepetko, Are Martin Holm, Diane Van Kessel, Benoit Nemery, G. Meachery, Christian Benden, Danielle Vienneau, Erik-Jan Oudijk, Elly Vandermeulen, Cristina Berastegui, Esmée M. Bijnens, David Ruttens, Claus Neurohr, Erik A M Verschuuren, Jens Gottlieb, Antonio Roman, Geert Verleden, Robin Vos, Hans-Henrik Schultz, Urte Sommerwerck, Markus Kamler, Tim S. Nawrot, Hannelore Bellon, Johanna Kwakkel-van-Erp, Barbara Hoffmann, Wim van der Bij, Peter Jaksch, Federica Meloni, Stijn E. Verleden, Martin Iversen, Davide Piloni, Gerhard Weinreich, Paul A. Corris, Bart M. Vanaudenaerde, Gerard Hoek, Monica Morosini, Ellen Winckelmans, Susana Gómez-Ollés, Kees de Hoogh, James Lordan, Nikolaus Kneidinger, Gregor Warnecke, Andrew J. Fisher, and Bart Luijk
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Pollution ,medicine.medical_specialty ,Proportional hazards model ,business.industry ,medicine.medical_treatment ,media_common.quotation_subject ,Incidence (epidemiology) ,Air pollution ,Patient characteristics ,medicine.disease_cause ,Surgery ,Internal medicine ,medicine ,Lung transplantation ,In patient ,business ,media_common - Abstract
It has been suggested that air pollution influences survival after lung transplantation (LTx).We investigated the association of long-term exposure to fine particles and traffic with mortality and chronic lung allograft dysfunction (CLAD).In 13 European LTx centers, patient characteristics were retrospectively collected. Patients transplanted 700 km from LTx center were excluded, resulting in 5,707 LTx patients. We estimated long-term particulate matter (PM 10 ) exposure at home addresses with temporally adjusted land-use regression models and total road length within buffers zones around the home and using Cox regression. We associated this with incidence of CLAD and mortality, separately for patients taking macrolides or not. During follow-up (median 4.2 y), 2,767 patients developed CLAD and 2,718 died. In patients not taking AZI (n=3,551) air-pollution was associated with mortality and CLAD independent of covariates.The risk for dying increased by 22.0% for patients living in an area above the WHO air pollution standards (20 µg/m³) compared with residence
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- 2015
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18. Total Lymphoid Irradiation (TLI) for the Management of Bronchiolitis Obliterans Syndrome (BOS) Post Lung Transplant: A Single Centre Experience
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Gareth Parry, Andrew J. Fisher, R. Miller, B. Hartog, James Lordan, Paul A. Corris, J. Frew, and G. Meachery
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Pulmonary and Respiratory Medicine ,Gerontology ,Transplantation ,Pathology ,medicine.medical_specialty ,Lung ,business.industry ,Bronchiolitis obliterans ,Total lymphoid irradiation ,030230 surgery ,medicine.disease ,03 medical and health sciences ,Single centre ,0302 clinical medicine ,medicine.anatomical_structure ,medicine ,030211 gastroenterology & hepatology ,Surgery ,Cardiology and Cardiovascular Medicine ,business - Published
- 2016
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19. 123 Prevalence of transmissible strains of Pseudomonas aeruginosa in a cystic fibrosis tertiary referral centre and lung transplant unit
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James Lordan, SJ Doe, A. Robb, T. Carroll, A. Nicholson, Kate Gould, D. Kenna, S. Peart, G. Meachery, and Stephen Bourke
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Pseudomonas aeruginosa ,Tertiary referral centre ,medicine.disease ,medicine.disease_cause ,Cystic fibrosis ,humanities ,City hospital ,Internal medicine ,Pediatrics, Perinatology and Child Health ,population characteristics ,Medicine ,Pediatrics, Perinatology, and Child Health ,business ,Intensive care medicine ,geographic locations - Abstract
120 Canine detection of Pseudomonas aeruginosa (PA) volatile organic compounds (VOC’s) N.V. Johnston1, J. Rao2, J.S. Elborn3,4, J.E. Moore5. 1Dogs Nose Ltd, Portadown, United Kingdom; 2University of Ulster, School of Biomedical Sciences, Coleraine, United Kingdom; 3Queen’s University Belfast, Centre for Infection and Immunity, Belfast, United Kingdom; 4Belfast City Hospital, Regional Adult Cystic Fibrosis Centre, Belfast, United Kingdom; 5Belfast City Hospital, Department of Bacteriology, Belfast, United Kingdom
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- 2012
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20. Targeted Antibiotic Prophylaxis for Lung Transplantation in Cystic Fibrosis Patients Colonised with Pseudomonas aeruginosa Using Multiple Combination Bactericidal Testing
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A. Nicholson, John D. Perry, James L. Lordan, Helmy Haja Mydin, G. Meachery, Paul A. Corris, Emma C. L. Marrs, F.K. Gould, Christine Fagan, S. Peart, and Andrew J. Fisher
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medicine.medical_specialty ,Article Subject ,medicine.drug_class ,Pseudomonas aeruginosa ,business.industry ,medicine.medical_treatment ,Antibiotics ,lcsh:Surgery ,lcsh:RD1-811 ,medicine.disease ,medicine.disease_cause ,Cystic fibrosis ,Empyema ,Surgery ,Sepsis ,Internal medicine ,medicine ,Lung transplantation ,Antibiotic prophylaxis ,business ,Complication ,Research Article - Abstract
Early infection is a recognised complication after lung transplantation in patients with cystic fibrosis (CF). Our centre uses multiple combination bactericidal testing (MCBT) when determining appropriate peritransplant prophylactic regimens. To evaluate our strategy, we compared the incidence of posttransplant infection in patients whose peritransplant antimicrobial regimens were determined using MCBT versus standard sensitivity testing. Patients with CF who were infected withPseudomonas aeruginosaand underwent lung transplantations between 2000 and 2010 were included. Data was collected from clinical records and our microbiology database. Microorganisms cultured were mapped against antibiotic resistance, method of sensitivity testing, and antibiotics administered peritransplant. 129 patients were identified (mean age 28, male : female, 63 : 66). Fifty patients (38.8%) had antibiotics determined by MCBT. Two patients in the MCBT group developed septicaemia, 13 in the conventional group (P≤0.05, 2-tailed Fisher's test). Sepsis was attributable toP. aeruginosain one patient from the MCBT group and seven patients in the conventional group (P=0.15).P. aeruginosawas recovered from the posttransplant pleural fluid of one patient who received MCBT-guided prophylaxis, six patients in the conventional group (P=0.25). Patients given antibiotics based on MCBT had significantly lower rates of septicaemia and lower rates of empyema.
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- 2012
21. 285* The impact of BMI on survival of patients with cystic fibrosis undergoing lung transplantation: a single centre experience
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James Lordan, K. Hester, S. Wiscombe, Gareth Parry, Andrew J. Fisher, D. Anthony, Paul A. Corris, and G. Meachery
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,medicine.disease ,Cystic fibrosis ,Gastroenterology ,Single centre ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Lung transplantation ,Pediatrics, Perinatology, and Child Health ,business - Published
- 2011
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22. P243 A Retrospective Observational Study Of 20 Year Lung Transplant Survivors - A Single Centre Experience
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G. Meachery, Gareth Parry, Andrew J. Fisher, John H. Dark, Logan Thirugnanasothy, Asif Hasan, Sasiharan Sithamparanathan, James Lordan, Kate Gould, Paul A. Corris, Guy A. MacGowan, and Stephen Clark
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Interstitial lung disease ,Bronchiolitis obliterans ,Immunosuppression ,Retrospective cohort study ,medicine.disease ,Surgery ,Transplantation ,Internal medicine ,medicine ,Bronchitis ,Renal replacement therapy ,business ,Survival rate - Abstract
Introduction and objectives Lung transplant patients have a reduced survival rate compared to other solid organ recipients. Chronic lung allograft dysfunction (CLAD) remains the main factor in limiting longevity in lung transplant patients, with 50% of recipients developing Bronchiolitis Obliterans Syndrome (BOS) by 5.6 years. There is a lack of published data on the course and history of long term survivors and we describe characteristics and outcomes of all lung transplant recipients who have survived greater than 20 years at our centre. Results Twenty-one (16.2%) out of a possible total of 121 transplant patients survived at least 20 years with an overall median survival of 21.3 (range 20.1–24.9) years. The mean age at transplantation was 31.8 ± 9.9 years and 13 (61.9%) were male. The most common indication for transplantation in the group was Cystic Fibrosis (33.3%); heart-lung and bilateral lung transplant operations were equally the most commonly performed. The median six-minute walk distance (6MWD) was 600m (range 419–785m). The median time to the development of BOS was 9.7 years. At time of evaluation, 2 (10%) patients had BOS score 0, 3 (14%) BOS 1, 6 (29%) BOS 2 and 10 (48%) BOS 3. The total number of rejections requiring augmentation with corticosteroids was 30 episodes in 21 patients with an average of 1.4 (range 0–3) episodes per patient. Eighteen patients had at least one episode of rejection needing corticosteroids. No patient developed symptomatic ischaemic heart disease; systemic hypertension was found in 19 (90.5%) patients. Two (9.5%) patients developed post-transplant lymphoproliferative disease. Four patients developed other malignancies, 3 of which were skin cancers and 1 renal cancer. All 4 cases of diabetes post transplantation occurred in patients with Cystic Fibrosis. Eight patients required renal replacement therapy as a result of ciclosporin toxicity and four underwent renal transplantation. Conclusion Twenty-one (16.2%) patients in our cohort survived 20 years. Although nearly all patients developed an element of CLAD, exercise tolerance was preserved as judged by 6MWD. Hypertension was common and renal failure remained the most problematic complication of immunosuppression.
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- 2014
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23. Outcomes of lung transplantation for cystic fibrosis in a large UK cohort
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Gareth Parry, A. Nicholson, Andrew J. Fisher, A De Soyza, Asif Hasan, F.K. Gould, James L. Lordan, G. Meachery, Stephen Clark, S. Schueler, Paul A. Corris, J.H. Dark, Thasee Pillay, and K. Tocewicz
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Pulmonary and Respiratory Medicine ,Adult ,Male ,Reoperation ,medicine.medical_specialty ,Adolescent ,Cystic Fibrosis ,medicine.medical_treatment ,Bronchiolitis obliterans ,Cystic fibrosis ,Pulmonary function testing ,Diabetes Complications ,Postoperative Complications ,Renal Dialysis ,Internal medicine ,Neoplasms ,Preoperative Care ,medicine ,Lung transplantation ,Humans ,Child ,Bronchiolitis Obliterans ,business.industry ,Respiratory disease ,Interstitial lung disease ,Sputum ,Middle Aged ,medicine.disease ,United Kingdom ,Surgery ,Transplantation ,Airway Obstruction ,Bronchitis ,Female ,Kidney Diseases ,business ,Epidemiologic Methods ,Bronchoalveolar Lavage Fluid ,Lung Transplantation - Abstract
Background: Lung transplantation is an important option to treat patients with advanced Cystic Fibrosis (CF) lung disease. We report the outcomes of a large UK cohort of CF lung transplantation recipients. Methods: Retrospective review of case notes and transplantation databases. Results 176 patients with CF underwent lung transplantation at our centre. The majority (168) had bilateral sequential lung transplantation. Median age at transplantation was 26 years. Diabetes was common pre-transplantation (40%). Polymicrobial infection was common in individual recipients. A diverse range of pathogens were encountered including the Burkholderia cepacia complex (BCC). The bronchial anastomotic complication rate was 2%. Pulmonary function (FEV1% predicted) improved from pre-transplantation median 0.8 litres (21% predicted) to 2.95 litres (78% predicted) at one year following transplantation. We noted an acute rejection rate of 41% within the first month. Our survival figures were 82% survival at one year, 70% at three years, 62% at five years and 51% at ten years. Patients with BCC infection had poorer outcomes and represented the majority of those who had a septic death. We present data on those free from these infections. Bronchiolitis Obliterans Syndrome (BOS) and sepsis were common causes of death. Freedom from BOS was 74% at five years and 38 % at ten years. Biochemical evidence of renal dysfunction was common though renal replacement was infrequently required (
- Published
- 2008
24. Methotrexate as a Treatment Strategy for Bronchiolitis Obliterans Syndrome (BOS)
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James Lordan, Gareth Parry, G. Meachery, Andrew J. Fisher, Katie Morley, Paul A. Corris, Logan Thirugnanasothy, and Sasiharan Sithamparanathan
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Pulmonary and Respiratory Medicine ,Transplantation ,medicine.medical_specialty ,business.industry ,Bronchiolitis obliterans ,medicine.disease ,Dermatology ,Immunology ,Medicine ,Treatment strategy ,Surgery ,Methotrexate ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Published
- 2015
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25. Most Effective In Vitro Antimicrobials for Treatment of Stenotrophomonas Maltophilia Infections in Cystic Fibrosis Lung Transplant Recipients
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S. Peart, D. Tierney, Audrey Perry, F.K. Gould, John D. Perry, and G. Meachery
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Pulmonary and Respiratory Medicine ,Gerontology ,Oncology ,Transplantation ,medicine.medical_specialty ,Lung ,biology ,business.industry ,Disease progression ,Antimicrobial ,medicine.disease ,biology.organism_classification ,Cystic fibrosis ,In vitro ,Public access ,Stenotrophomonas maltophilia ,medicine.anatomical_structure ,Internal medicine ,Potential biomarkers ,medicine ,Surgery ,Cardiology and Cardiovascular Medicine ,business - Abstract
s S307 (p= 6.22e-06 for interaction) and may play a role in disease progression and impaired myocardial energetics. Conclusion: A bioinformatic analysis may identify previously unreported miRs potentially involved in HF development. This is a novel approach using public access data for identify potential biomarkers of subjects with high risk for HF development or progression. FONDAP 15130011 ACCDIS.
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- 2015
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26. Improving Outcomes in Lung Transplantation for Cystic Fibrosis – A Unified Approach
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Gareth Parry, Andrew J. Fisher, Paul A. Corris, G. Meachery, Katie Morley, James Lordan, Kate Gould, Audrey Perry, K. Tocewicz, John H. Dark, A. M. Ranasinghe, Thasee Pillay, Leslie Hamilton, Stephan Schueler, and Stephen Clark
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Pulmonary and Respiratory Medicine ,Transplantation ,medicine.medical_specialty ,Lung ,business.industry ,medicine.medical_treatment ,Pleural cavity ,medicine.disease ,Cystic fibrosis ,law.invention ,Surgery ,Pneumonectomy ,medicine.anatomical_structure ,law ,Cardiopulmonary bypass ,medicine ,Lung transplantation ,Airway management ,Cardiology and Cardiovascular Medicine ,business - Abstract
Purpose We report outcomes of a large UK cohort of adult Cystic Fibrosis(CF) patients undergoing bilateral sequential lung transplantation(BLT) at a single institution. Methods and Materials We searched our prospectively maintained database for patients undergoing lung transplantation (LT) for CF between 01/89-11/12. Survival was censored at 7/11/12. A unified approach to BLT has been undertaken in these patients. Including targeted antibiotic prophylaxis, pleural cavity and central airway taurolidine irrigation, surgery (clamshell incision) on full cardiopulmonary bypass (CPB) (off-pump or extra-corporeal membrane oxygenation (ECMO) not used), bilateral pneumonectomy prior to donor implant and synchronous controlled reperfusion. Since 12/07, a genomovar specific policy has been adopted and patients colonized with Burkholderia cenocepacia have been excluded from LT. Results A total of 270 LT for CF were performed during this period. Included in this were two single lungs (with synchronous pneumonectomy), one living donor lobar transplant, four heart-lung (pre-1990) and two lung-liver. Of the 261 remaining, 253 were performed in adults (cohort analyzed). There were 118 (47%) males, median (range) age 27.4 (16.5-32.7) years. Mean [95%CI] BMI at assessment was 19.6 [19.2-19.9]. Median time to transplantation from listing was 305 (4-2190) days. Median ischemic time was 340 (131-601) mins. Survival at 1, 3, 5 and 10 years was 83%, 74%, 65% and 53%. There was a trend to improved late survival for patients transplanted post vs. pre-2000; 84 vs. 79%, 76 vs. 68%, 67 vs. 58% and 56 vs. 45% (p = 0.106). Conclusions In this large single centre experience of BLT for CF, our institutional operative strategy utilizing full CPB(not ECMO) for all cases, with recipient bilateral pneumonectomy prior to implantation simplifies airway management, virtually eliminates pleural spillage and excludes possible spillage from recipient to donor lung. Our standardized and simplified approach yields excellent and improving results in this challenging group of patients.
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- 2013
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27. 437 Misidentification of Burkholderia cenocepacia and the Implications for Lung Transplantation for Cystic Fibrosis
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David A. Spencer, S. Peart, Paul A. Corris, A. Nicholson, F.K. Gould, John D. Perry, Andrew J. Fisher, G. Meachery, Emma C. L. Marrs, D. Kenna, and J. Lordon
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Pulmonary and Respiratory Medicine ,Transplantation ,Pathology ,medicine.medical_specialty ,Burkholderia cenocepacia ,biology ,business.industry ,medicine.medical_treatment ,biology.organism_classification ,medicine.disease ,Cystic fibrosis ,medicine ,Lung transplantation ,Surgery ,Cardiology and Cardiovascular Medicine ,business - Published
- 2011
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28. 185: Survival outcomes following lung transplantation for cystic fibrosis patients infected with Burkholderia cenocepacia – a UK experience
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James Lordan, G. Meachery, Stephen Clark, L. Archer, A De Soyza, F.K. Gould, Gareth Parry, Paul A. Corris, Andrew J. Fisher, K. Tocewicz, J.H. Dark, and S. Schueler
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Pulmonary and Respiratory Medicine ,Transplantation ,medicine.medical_specialty ,Bronchiectasis ,Burkholderia cenocepacia ,biology ,business.industry ,medicine.medical_treatment ,medicine.disease ,biology.organism_classification ,Cystic fibrosis ,Gastroenterology ,Internal medicine ,Long term survival ,Immunology ,medicine ,Lung transplantation ,Surgery ,Cardiology and Cardiovascular Medicine ,business - Abstract
32% vs 44%; IPF 29% vs 25%; Bronchiectasis 23% vs 13%; NS), Pre-LTx PaO2 (49 vs 49 mmHg) 6MWT distance (292 vs 276 mts) or LTx procedure (BLTx 65% vs 69%). 51% of patients developed episodes of acute rejection, 52% EED and 44% NHBD (NS). Grade A2 or greater rejection was observed in 39% EDD and 38% NHBS (NS). No significant differences were observed in long term survival (Figure 1) or BOS (Figure 2). Conclusions: These data show that NHBD are similar to EDD in terms of long term survival and chronic rejection.
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- 2007
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29. Influenza: an outbreak in a UK respiratory centre
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Avinash Aujayeb, S Gray, R Fagg, S Waugh, G. Meachery, K Walton, Sophie West, J Samuel, A Russell, and M Valappil
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medicine.medical_specialty ,business.industry ,Influenza A Virus, H3N2 Subtype ,Outbreak ,medicine.disease_cause ,United Kingdom ,Disease Outbreaks ,Influenza, Human ,Emergency medicine ,Influenza A virus ,medicine ,Humans ,Health Facilities ,Respiratory system ,business ,General Nursing - Published
- 2013
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30. P243 Influenza A outbreak in a UK respiratory centre
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R Fagg, Sophie West, A Russel, S Waugh, C Walton, G. Meachery, Avinash Aujayeb, J Samuel, and S Gray
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Oseltamivir ,Isolation (health care) ,business.industry ,media_common.quotation_subject ,Respiratory infection ,Vaccination ,chemistry.chemical_compound ,chemistry ,Hygiene ,Emergency medicine ,medicine ,Infection control ,Intensive care medicine ,business ,Index case ,Contact tracing ,media_common - Abstract
Introduction In March 2013, 12 patients on a single ward in a tertiary respiratory transplant centre contracted influenza within 72 hours. There was no corresponding community outbreak. Staff with symptoms went off sick. Trust policies outlining respiratory infection and isolation existed but there were no guidelines for this specific novel situation. We found no published reports of such an event in England. Methods Patients quickly developed pyrexias and respiratory symptoms. All had throat swabs and blood cultures. Influenza A, H3N2 variant, was identified. A team of infection control and respiratory physicians, nurses and managers met regularly to implement these measures: Closure of ward and cohorting of bays Ward avoidance for non-essential personnel and anyone with symptoms Cancellation of non-essential procedures Strict hand hygiene and use of PPE and FFP3 masks Stockage of oseltamivir for treatment for all affected high risk staff and patients and prophylaxis offered to all ward patients and exposed high risk staff. No crossover of ward staff to transplant patients. Contact tracing of all immunocompromised patients on ward up to one week and all high risk patients 48 hours prior to the index case; advice on prophylaxis and their GPs contacted. Writing an information sheet for staff and GPs Increased and terminal ward cleaning Results On the respiratory ward, 151 bed days were lost and 53 on two other wards. Fourteen patients (including two on another ward) had positive swabs for H3N2. There were 27 symptomatic staff members; 15 had swabs, two were positive. All patients and two staff members were given treatment oseltamivir. Fourteen patients and two staff members had prophylaxis. No influenza complications or deaths occurred. The department staff had 45% influenza vaccination uptake in 2012/2013. All affected patients had been vaccinated. Conclusions Containment, pathogen identification, prompt treatment and contact tracing were priorities, to limit number of individuals affected. This is widely applicable. Our departmental staff vaccination rate is below Department of Health targets. Importance of vaccination needs emphasising, whilst recognising that vaccine effectiveness against all laboratory-confirmed influenza in primary care is 51% for 2012/2013.
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- 2013
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31. Pregnancy after Lung Transplantation: A Single Center Experience
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James Lordan, G. Meachery, Katie Morley, Paul A. Corris, Gareth Parry, Andrew J. Fisher, and Mitesh V. Thakrar
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Pulmonary and Respiratory Medicine ,Spirometry ,Transplantation ,medicine.medical_specialty ,Pregnancy ,medicine.diagnostic_test ,business.industry ,Obstetrics ,medicine.medical_treatment ,Renal function ,Single Center ,medicine.disease ,Surgery ,Preeclampsia ,FEV1/FVC ratio ,medicine ,Lung transplantation ,Cardiology and Cardiovascular Medicine ,business ,Complication - Abstract
Purpose Advances in lung transplantation have enabled women to successfully undertake pregnancies. We maintain they be at least 2 years post transplant and complication free before pregnancy. This study explores maternal outcomes in pregnancy, including changes in lung and renal function, and calcineurin inhibitor (CNI) levels. Methods and Materials A retrospective audit of lung transplants in Newcastle was undertaken. We identified patients who had ever become pregnant; manual reviews of their medical records were completed. Results of spirometry, serum creatinine, CNI doses and trough levels, and comorbidities were collected. Changes in spirometry were compared using a student t-test; p-values Results There have been 16 pregnancies (complete records available for 12), with 7 live births (44% success rate), amongst 13 patients. Six patients have since died, with one death occurring early post-pregnancy. 5 pregnancies were unplanned, with only one resulting in birth. In all, 5 pregnancies ended with spontaneous miscarriage, while 2 were terminated for medical reasons (one ectopic, one for unstable BOS preconception). Mean age at time of pregnancy was 30.4 years (range 22–39), and mean time from transplant was 35.9 months (range 26–139). Complications included preeclampsia (2, 17%), diabetes of pregnancy (1, 8%), and abnormal liver enzymes (1, 8%). Within six months of delivery, there were 2 pneumonias (17%), 2 cases of BOS (17%), one case of TB (8%) and one case of mild acute rejection (8%). Mean change in FEV1 during full-term pregnancies was -2.4% (range -8.7% to 12.4%, p=0.42) and mean change in FVC was +2.7% (range -1.7% to 11.2%, p=0.55). FEV1 was stable 3 and 12 months after pregnancy (-0.3%, p=0.55 and +2.5%, p=0.69). In the first trimester, 60% had a fall in creatinine and a universal fall in CNI trough levels (mean change -42%) was seen. Conclusions In carefully selected patients, pregnancy after lung transplant can be successful. However, complications are common and close monitoring of immunosuppression levels and renal function are needed.
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- 2013
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32. 173 A Randomised Controlled Trial of Azithromycin Therapy in Bronchiolitis Obliterans Syndrome (BOS) Post Lung Transplantation
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P.A. Corris, T. Small, V.A. Ryan, J. Lordan, A.J. Fisher, G. Meachery, G. Johnson, and C. Ward
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Pulmonary and Respiratory Medicine ,Transplantation ,Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2012
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33. 812 Prospective Evaluation of Alveolar and Bronchiolar C4d Expression in Transbronchial Biopsies from Lung Transplanted Recipients
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G. Meachery, James Lordan, Andrew J. Fisher, N. Thampy, J. Majo, Fiona Black, Rahul Y Mahida, and Paul A. Corris
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Pulmonary and Respiratory Medicine ,Transplantation ,Pathology ,medicine.medical_specialty ,Lung ,business.industry ,education ,respiratory system ,Prospective evaluation ,medicine.anatomical_structure ,Newcastle upon tyne ,medicine ,Surgery ,Cardiology and Cardiovascular Medicine ,business - Abstract
Prospective Evaluation of Alveolar and Bronchiolar C4d Expression in Transbronchial Biopsies from Lung Transplanted Recipients J. Majo, R. Mahida, N. Thampy, F. Black, G. Meachery, J.L. Lordan, P.A. Corris, A.J. Fisher. Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, England, United Kingdom; Institute of Cellular Medecine, Newcastle University, Newcastle upon Tyne, England, United Kingdom.
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- 2012
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34. 103 Targeted Antibiotic Prophylaxis for Lung Transplantation in Cystic Fibrosis Patients Colonised with Pseudomonas Aeruginosa
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Paul A. Corris, F.K. Gould, S. Peart, Andrew J. Fisher, James Lordan, G. Meachery, Helmy Haja Mydin, C. Fagan, and A. Nicholson
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Pulmonary and Respiratory Medicine ,Transplantation ,medicine.medical_specialty ,Pseudomonas aeruginosa ,business.industry ,medicine.medical_treatment ,medicine.disease_cause ,medicine.disease ,Gastroenterology ,Cystic fibrosis ,Internal medicine ,Immunology ,medicine ,Lung transplantation ,Surgery ,Antibiotic prophylaxis ,Cardiology and Cardiovascular Medicine ,business - Published
- 2011
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35. 277* Outcome following lung transplantation for patients with cystic fibrosis related liver disease: a single centre experience
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G. Meachery, James Lordan, K. Hester, Gareth Parry, Andrew J. Fisher, D. Anthony, Paul A. Corris, and S. Wiscombe
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,medicine.disease ,Cystic fibrosis ,Gastroenterology ,Single centre ,Liver disease ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Lung transplantation ,Pediatrics, Perinatology, and Child Health ,business - Full Text
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36. Outcomes of listing for lung and heart-lung transplantation in pulmonary hypertension: comparative experience in France and the UK.
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Pradère P, Le Pavec J, Bos S, Pozza A, Nair A, Meachery G, Lordan J, Humbert M, Mercier O, Fadel E, Savale L, and Fisher AJ
- Abstract
Background: Lung or heart-lung transplantation (LT/HLT) for severe pulmonary hypertension (PH) as the primary disease indication carries a high risk of waiting list mortality and post-transplant complications. France and the UK both have coordinated PH patient services but with different referral pathways for accessing LT services., Methods: We conducted a comparative analysis of adult PH patients listed for LT/HLT in the UK and France., Results: We included 211 PH patients in France (2006-2018) and 170 in the UK (2010-2019). Cumulative incidence of transplant, delisting and waiting list death within 3 years were 81%, 4% and 11% in France versus 58%, 10% and 15% in the UK (p<0.001 for transplant and delisting; p=0.1 for death). Median non-priority waiting time was 45 days in France versus 165 days in the UK (p<0.001). High-priority listing occurred in 54% and 51% of transplanted patients respectively in France and the UK (p=0.8). Factors associated with achieving transplantation related to recipients' height, male sex, clinical severity and priority listing status. 1-year post-transplant survival was 78% in France and 72% in the UK (p= 0.04)., Conclusion: Access to transplantation for PH patients is better in France than in the UK where more patients were delisted due to clinical deterioration because of longer waiting time. High rates of priority listing occurred in both countries. Survival for those achieving transplantation was slightly better in France. Ensuring optimal outcomes after transplant listing for PH patients is challenging and may involve early listing of higher risk patients, increasing donor lung utilisation and improving allocation rules for these specific patients., Competing Interests: Conflict of interest: P. Pradère, J. Le Pavec, A. Pozza, G. Meachery, O. Mercier and E. Fadel have nothing to declare. Conflict of interest: S. Bos received lecture fees from Therakos (Mallinckrodt) and Jazz, and conference registration/travel support from GlaxoSmithKline and Takeda, outside of the submitted work. Conflict of interest: A. Nair received personal fees from Janssen, outside of the submitted work. Conflict of interest: J. Lordan reports travel support from Johnson and Johnson outside the submitted work and an honorarium from MSD for a PH advisory board meeting. Conflict of interest: M. Humbert reports grants from AOP Orphan, Janssen and Shou Ti; consulting fees from Aerovate, Altavant, AOP Orphan, Chiesi, Ferrer, Janssen, MorphogenIX, Shou Ti, Tiakis and United Therapuetics; lecture honoraria from Janssen; grants, consulting fees and personal fees for advisory board participation from Acceleron; grants and personal fees from Actelion; grants, consulting fees and personal fees from Bayer; personal fees from GSK; grants, consulting fees, lecture honoraria and personal fees for advisory board participation from Merck; personal fees from Novartis; personal fees from AstraZeneca; personal fees from Sanofi; and advisory board participation from Altavant, Janssen and United Therapeutics, outside the submitted work. Conflict of interest: L. Savale reports personal fees from Actelion, personal fees from MSD, grants and personal fees from GSK, outside the submitted work. Conflict of interest: A.J. Fisher reports grants from GlaxoSmithKline, grants, personal fees and nonfinancial support from Mallinckrodt Pharmaceuticals, personal fees from Altavant, and grants from Pfizer, outside the submitted work., (Copyright ©The authors 2024.)
- Published
- 2024
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37. Silicone depositions: an unusual finding in the explanted and newly transplanted lungs.
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Bos S, Majo J, Funston W, Fisher AJ, and Meachery G
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- Humans, Lung diagnostic imaging, Silicones adverse effects, Lung Transplantation adverse effects
- Abstract
Competing Interests: Competing interests: None declared.
- Published
- 2023
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38. Lung transplantation for interstitial lung disease: evolution over three decades.
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Leong SW, Bos S, Lordan JL, Nair A, Fisher AJ, and Meachery G
- Subjects
- Humans, Retrospective Studies, Phenotype, Lung Diseases, Interstitial surgery, Lung Transplantation, Idiopathic Pulmonary Fibrosis surgery
- Abstract
Background: Interstitial lung disease (ILD) has emerged as the most common indication for lung transplantation globally. However, post-transplant survival varies depending on the underlying disease phenotype and comorbidities. This study aimed to describe the demographics, disease classification, outcomes and factors associated with post-transplant survival in a large single-centre cohort., Methods: Data were retrospectively assessed for 284 recipients who underwent lung transplantation for ILD in our centre between 1987 and 2020. Patient characteristics and outcomes were stratified by three eras: 1987-2000, 2001-2010 and 2011-2020., Results: Median patients' age at time of transplantation was significantly higher in the most recent decade (56 (51-61) years, p<0.0001). Recipients aged over 50 years had worse overall survival compared with younger patients (adjusted HR, aHR 2.36, 95% CI 1.55 to 3.72, p=0.0001). Better survival was seen with bilateral versus single lung transplantation in patients younger than 50 years (log-rank p=0.0195). However, this survival benefit was no longer present in patients aged over 50 years. Reduced survival was observed in fibrotic non-specific interstitial pneumonia compared with idiopathic pulmonary fibrosis, which remained the most common indication throughout (aHR 2.61, 95% CI 1.40 to 4.60, p=0.0015)., Conclusion: In patients transplanted for end-stage ILD, older age and fibrotic non-specific interstitial pneumonia were associated with poorer post-transplant survival. The benefit of bilateral over single lung transplantation diminished with increasing age, suggesting that single lung transplantation might still be a feasible option in older candidates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
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39. Diagnosis and predicted outcomes of patients with cystic fibrosis related liver disease considered for lung transplantation.
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Khoshbin E, Clark S, Meachery G, Fisher A, De Soyza A, Lordan J, Nair A, Dark J, and Hudson M
- Subjects
- Aspartate Aminotransferases, Biomarkers, Biopsy, Humans, Liver pathology, Liver Cirrhosis pathology, Platelet Count, Severity of Illness Index, Cystic Fibrosis complications, Cystic Fibrosis diagnosis, Cystic Fibrosis surgery, Liver Diseases diagnosis, Liver Diseases etiology, Liver Diseases surgery, Lung Transplantation adverse effects
- Abstract
Introduction: There is no gold standard criterion for the diagnosis of cystic fibrosis-related liver disease (CFRLD) and there is uncertainty over its impact on the outcome of lung transplantation., Method: Lung recipients (n = 238) were divided into two groups-CFRLD and non-CFRLD based on a modified aspartate aminotransferase-to-platelet ratio index (APRI) score (mAPRI) to diagnose CFRLD and predict severity of liver disease. Groups were compared to assess validity of the diagnosis and survival outcomes., Result: The new diagnostic criterion was effective at differentiating CFRLD from non-CFRLD. There was no significant difference in the survival between two groups at short, medium, or long term demonstrated by the Kaplan-Meier plot with survival of 85%, 73%, 47%, 18.6%, and 4.7% at 1, 2, 5, 10, and 15 years respectively. A mAPRI score of greater than .2 had a sensitivity of 43.0% but a specificity of 82.5 % for diagnosis of CFRLD and 46.5% sensitivity but 100% specificity in predicting an ultrasound/biopsy proven hepatic abnormality associated with CFRLD., Conclusion: A mAPRI sore is a highly specific non-invasive tool for diagnosis of CFRLD. Recipients with CFRLD but grossly preserved hepatocellular function have a similar outcome to patients without CFRLD., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2022
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40. Recovering the lung transplant service after COVID-19 - experience at the Freeman Hospital, Newcastle.
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Umair F, Athar MW, Nair A, Lordan J, Fisher A, and Meachery G
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- Hospitals, Humans, SARS-CoV-2, COVID-19, Lung Transplantation
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- 2021
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41. Outcomes of lung transplantation in adults with bronchiectasis.
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Birch J, Sunny SS, Hester KLM, Parry G, Kate Gould F, Dark JH, Clark SC, Meachery G, Lordan J, Fisher AJ, Corris PA, and De Soyza A
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- Adult, Bronchiectasis mortality, Databases, Factual, Female, Forced Expiratory Volume, Humans, Lung physiopathology, Male, Middle Aged, Postoperative Complications epidemiology, Pseudomonas Infections epidemiology, Retrospective Studies, Survival Analysis, Time Factors, Young Adult, Bronchiectasis microbiology, Bronchiectasis surgery, Lung Transplantation
- Abstract
Background: Lung transplantation is a well-established treatment for end-stage non-cystic fibrosis bronchiectasis (BR), though information regarding outcomes of transplantation remains limited. Our results of lung transplantation for Br are reported here., Methods: A retrospective review of case notes and transplantation databases was conducted for patients that had underwent lung transplantation for bronchiectasis at the Freeman Hospital between 1990 and 2013., Results: Fourty two BR patients underwent lung transplantation, the majority (39) having bilateral sequential lung transplantation. Mean age at transplantation was 47.1 years. Pre-transplantation osteoporosis was a significant non-pulmonary morbidity (48%). Polymicrobial infection was common, with Pseudomonas aeruginosa infection frequently but not universally observed (67%). Forced expiratory volume in 1 second (% predicted) improved from a pre-transplantation mean of 0.71 L (22% predicted) to 2.56 L (79 % predicted) at 1-year post-transplantation. Our survival results were 74% at 1 year, 64% at 3 years, 61% at 5 years and 48% at 10 years. Sepsis was a common cause of early post-transplantation deaths., Conclusions: Lung transplantation for end-stage BR is a useful therapeutic option, with good survival and lung function outcomes. Survival values were similar to other bilateral lung transplants at our centre. Pre-transplantation Pseudomonas infection is common.
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- 2018
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42. An association of particulate air pollution and traffic exposure with mortality after lung transplantation in Europe.
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Ruttens D, Verleden SE, Bijnens EM, Winckelmans E, Gottlieb J, Warnecke G, Meloni F, Morosini M, Van Der Bij W, Verschuuren EA, Sommerwerck U, Weinreich G, Kamler M, Roman A, Gomez-Olles S, Berastegui C, Benden C, Holm AM, Iversen M, Schultz HH, Luijk B, Oudijk EJ, Kwakkel-van Erp JM, Jaksch P, Klepetko W, Kneidinger N, Neurohr C, Corris P, Fisher AJ, Lordan J, Meachery G, Piloni D, Vandermeulen E, Bellon H, Hoffmann B, Vienneau D, Hoek G, de Hoogh K, Nemery B, Verleden GM, Vos R, Nawrot TS, and Vanaudenaerde BM
- Subjects
- Adult, Air Pollutants analysis, Cohort Studies, Europe epidemiology, Female, Graft Survival, Humans, Macrolides therapeutic use, Male, Middle Aged, Particulate Matter analysis, Proportional Hazards Models, Regression Analysis, Air Pollution adverse effects, Environmental Exposure adverse effects, Lung Transplantation mortality, Primary Graft Dysfunction physiopathology
- Abstract
Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies.13 lung transplant centres in 10 European countries created a cohort of 5707 patients. For each patient, we quantified residential particulate matter with aerodynamic diameter ≤10 µm (PM
10 ) by land use regression models, and the traffic exposure by quantifying total road length within buffer zones around the home addresses of patients and distance to a major road or freeway.After correction for macrolide use, we found associations between air pollution variables and CLAD/mortality. Given the important interaction with macrolides, we stratified according to macrolide use. No associations were observed in 2151 patients taking macrolides. However, in 3556 patients not taking macrolides, mortality was associated with PM10 (hazard ratio 1.081, 95% CI 1.000-1.167); similarly, CLAD and mortality were associated with road lengths in buffers of 200-1000 and 100-500 m, respectively (hazard ratio 1.085- 1.130). Sensitivity analyses for various possible confounders confirmed the robustness of these associations.Long-term residential air pollution and traffic exposure were associated with CLAD and survival after lung transplantation, but only in patients not taking macrolides., (Copyright ©ERS 2017.)- Published
- 2017
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43. A randomised controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation.
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Corris PA, Ryan VA, Small T, Lordan J, Fisher AJ, Meachery G, Johnson G, and Ward C
- Subjects
- Adult, Bronchiolitis Obliterans diagnosis, Bronchiolitis Obliterans etiology, Double-Blind Method, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Syndrome, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Azithromycin therapeutic use, Bronchiolitis Obliterans drug therapy, Lung Transplantation adverse effects
- Abstract
Background: We conducted a placebo-controlled trial of azithromycin therapy in bronchiolitis obliterans syndrome (BOS) post lung transplantation., Methods: We compared azithromycin (250 mg alternate days, 12 weeks) with placebo. Primary outcome was FEV1 change at 12 weeks., Results: 48 patients were randomised; (25 azithromycin, 23 placebo). It was established, post randomisation that two did not have BOS. 46 patients were analysed as intention to treat (ITT) with 33 'Completers'. ITT analysis included placebo patients treated with open-label azithromycin after study withdrawal., Outcome: The ITT analysis (n=46, 177 observations) estimated mean difference in FEV1 between treatments (azithromycin minus placebo) was 0.035 L, with a 95% CI of -0.112 L to 0.182 L (p=0.6). Five withdrawals, who were identified at the end of the study as having been randomised to placebo (four with rapid loss in FEV1, one withdrawn consent) had received rescue open-label azithromycin, with improvement in subsequent FEV1 at 12 weeks. Study Completers showed an estimated mean difference in FEV1 between treatment groups (azithromycin minus placebo) of 0.278 L, with 95% CI for the mean difference: 0.170 L to 0.386 L (p=<0.001). Nine of 23 ITT patients in the azithromycin group had ≥10% gain in FEV1 from baseline. No patients in the placebo group had ≥10% gain in FEV1 from baseline while on placebo (p=0.002). Seven serious adverse events, three azithromycin, four in the placebo group, were deemed unrelated to study medication., Conclusions: Azithromycin therapy improves FEV1 in patients with BOS and appears superior to placebo. This study strengthens evidence for clinical practice of initiating azithromycin therapy in BOS., Trial Registration Number: EU-CTR, 2006-000485-36/GB., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
- Published
- 2015
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44. Targeted Antibiotic Prophylaxis for Lung Transplantation in Cystic Fibrosis Patients Colonised with Pseudomonas aeruginosa Using Multiple Combination Bactericidal Testing.
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Haja Mydin H, Corris PA, Nicholson A, Perry JD, Meachery G, Marrs EC, Peart S, Fagan C, Lordan JL, Fisher AJ, and Gould FK
- Abstract
Early infection is a recognised complication after lung transplantation in patients with cystic fibrosis (CF). Our centre uses multiple combination bactericidal testing (MCBT) when determining appropriate peritransplant prophylactic regimens. To evaluate our strategy, we compared the incidence of posttransplant infection in patients whose peritransplant antimicrobial regimens were determined using MCBT versus standard sensitivity testing. Patients with CF who were infected with Pseudomonas aeruginosa and underwent lung transplantations between 2000 and 2010 were included. Data was collected from clinical records and our microbiology database. Microorganisms cultured were mapped against antibiotic resistance, method of sensitivity testing, and antibiotics administered peritransplant. 129 patients were identified (mean age 28, male : female, 63 : 66). Fifty patients (38.8%) had antibiotics determined by MCBT. Two patients in the MCBT group developed septicaemia, 13 in the conventional group (P ≤ 0.05, 2-tailed Fisher's test). Sepsis was attributable to P. aeruginosa in one patient from the MCBT group and seven patients in the conventional group (P = 0.15). P. aeruginosa was recovered from the posttransplant pleural fluid of one patient who received MCBT-guided prophylaxis, six patients in the conventional group (P = 0.25). Patients given antibiotics based on MCBT had significantly lower rates of septicaemia and lower rates of empyema.
- Published
- 2012
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45. Outcomes of lung transplantation for cystic fibrosis in a large UK cohort.
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Meachery G, De Soyza A, Nicholson A, Parry G, Hasan A, Tocewicz K, Pillay T, Clark S, Lordan JL, Schueler S, Fisher AJ, Dark JH, Gould FK, and Corris PA
- Subjects
- Adolescent, Adult, Airway Obstruction mortality, Bronchiolitis Obliterans mortality, Bronchoalveolar Lavage Fluid microbiology, Child, Cystic Fibrosis microbiology, Cystic Fibrosis mortality, Diabetes Complications mortality, Epidemiologic Methods, Female, Humans, Kidney Diseases etiology, Kidney Diseases mortality, Male, Middle Aged, Neoplasms mortality, Postoperative Complications mortality, Preoperative Care, Renal Dialysis statistics & numerical data, Reoperation, Sputum microbiology, United Kingdom epidemiology, Cystic Fibrosis surgery, Lung Transplantation mortality, Postoperative Complications etiology
- Abstract
Background: Lung transplantation is an important option to treat patients with advanced cystic fibrosis (CF) lung disease. The outcomes of a large UK cohort of CF lung transplantation recipients is reported., Methods: Retrospective review of case notes and transplantation databases., Results: 176 patients with CF underwent lung transplantation at our centre. The majority (168) had bilateral sequential lung transplantation. Median age at transplantation was 26 years. Diabetes was common pretransplantation (40%). Polymicrobial infection was common in individual recipients. A diverse range of pathogens were encountered, including the Burkholderia cepacia complex (BCC). The bronchial anastomotic complication rate was 2%. Pulmonary function (forced expiratory volume in 1 s % predicted) improved from a pretransplantation median of 0.8 l (21% predicted) to 2.95 l (78% predicted) at 1 year following transplantation. We noted an acute rejection rate of 41% within the first month. Our survival values were 82% survival at 1 year, 70% at 3 years, 62% at 5 years and 51% at 10 years. Patients with BCC infection had poorer outcomes and represented the majority of those who had a septic death. Data are presented on those free from these infections. Bronchiolitis obliterans syndrome (BOS) and sepsis were common causes of death. Freedom from BOS was 74% at 5 years and 38% at 10 years. Biochemical evidence of renal dysfunction was common although renal replacement was infrequently required (<5%)., Conclusion: Lung transplantation is an important therapeutic option in patients with CF even in those with more complex microbiology. Good functional outcomes are noted although transplantation associated morbidities accrue with time.
- Published
- 2008
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46. Endotoxin up-regulates interleukin-18: potential role for gram-negative colonization in sarcoidosis.
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Kelly DM, Greene CM, Meachery G, O'Mahony M, Gallagher PM, Taggart CC, O'Neill SJ, and McElvaney NG
- Subjects
- Adult, Bronchoalveolar Lavage Fluid, Female, Humans, Lipopolysaccharides pharmacology, Male, RNA, Ribosomal, 16S analysis, Sarcoidosis, Pulmonary microbiology, T-Lymphocytes, Helper-Inducer physiology, Tuberculin pharmacology, Up-Regulation physiology, Gram-Negative Bacteria physiology, Interleukin-18 physiology, Sarcoidosis, Pulmonary physiopathology
- Abstract
Rationale and Objectives: Sarcoidosis is a granulomatous disease of unknown etiology characterized by a helper T-cell type 1-mediated process. Previously we demonstrated a role for interleukin-18 in sarcoidosis. Here we examine the regulation of interleukin-18 in this condition., Methods: Cytokine levels in sarcoid epithelial lining fluid were measured by ELISA. We examined interleukin-18 promoter activity and mRNA and protein levels in the epithelial lining fluid of individuals with active sarcoidosis, and of individuals recovered from sarcoidosis, in response to purified protein derivative of Mycobacterium tuberculosis, beryllium sulfate, zirconium sulfate, aluminum sulfate, and lipopolysaccharide. Endotoxin levels in the epithelial lining fluid of individuals with sarcoidosis, individuals recovered from sarcoidosis, and control subjects were assessed by Limulus amebocyte lysate analysis. Allele-specific polymerase chain reaction was used to genotype 94 patients with sarcoidosis and 97 control subjects for the interleukin-18 -607(A/C) polymorphism. Species-specific polymerase chain reaction identified bacterial DNA in fluid samples., Results: Epithelial lining fluid from active sarcoids contained elevated levels of interleukin-18, interferon-gamma, and interleukin-12 compared with recovered patients and also contained significantly higher levels of endotoxin. Depletion of endotoxin from this epithelial lining fluid reduced its effect on the human interleukin-18 promoter in vitro. There was a higher frequency of the -607C allele and -607(C/C) genotype in the sarcoidosis population compared with control subjects; however, this was not associated with a functional response to endotoxin treatment. Finally, bacterial 16S rRNA from Haemophilus influenzae and Moraxella catarrhalis was detected in sarcoid fluid samples., Conclusions: The pathogenesis of sarcoidosis is propagated through the actions of a helper T-cell type 1-driven response. This study shows that gram-negative bacteria may contribute to this effect by upregulating interleukin-18 expression.
- Published
- 2005
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47. Role of IL-18 in CD4+ T lymphocyte activation in sarcoidosis.
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Greene CM, Meachery G, Taggart CC, Rooney CP, Coakley R, O'Neill SJ, and McElvaney NG
- Subjects
- Adult, Bronchoalveolar Lavage Fluid immunology, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes pathology, Cytokines metabolism, Epithelium immunology, Epithelium metabolism, Female, Gene Expression Regulation immunology, Humans, Interleukin-18 metabolism, Interleukin-18 Receptor alpha Subunit, Interleukin-2 biosynthesis, Interleukin-2 genetics, Jurkat Cells immunology, Jurkat Cells metabolism, Male, Middle Aged, NF-kappa B metabolism, Receptors, Interleukin biosynthesis, Receptors, Interleukin blood, Receptors, Interleukin-18, Sarcoidosis, Pulmonary metabolism, Sarcoidosis, Pulmonary pathology, Th1 Cells immunology, Th1 Cells metabolism, Transcription Factor AP-1 blood, Transcription Factor AP-1 metabolism, Transcriptional Activation immunology, U937 Cells, CD4-Positive T-Lymphocytes immunology, Interleukin-18 physiology, Lymphocyte Activation immunology, Sarcoidosis, Pulmonary immunology
- Abstract
Sarcoidosis is a granulomatous disease of unknown etiology associated with the expansion of IL-2-producing activated CD4(+) T lymphocytes. A number of factors including the recently described IL-18 have been implicated in IL-2 expression in vitro. We investigated the role of IL-18 in IL-2 expression in sarcoidosis. Eighteen individuals with sarcoidosis and 15 normal controls were studied. IL-18R expression and epithelial lining fluid (ELF) concentrations of IL-18 were significantly elevated in the sarcoid group (p = 0.0143 and 0.0024, respectively). Both AP1 and NF-kappaB, transcription factors that regulate IL-2 gene expression, were activated in vivo in sarcoid pulmonary CD4(+) T lymphocytes. Transcription factor activity was not detected in pulmonary CD4(+) T lymphocytes from normal controls or from peripheral blood CD4(+) T lymphocytes from individuals with sarcoidosis, further evidence of compartmentalization of the lymphoproliferative process in this condition. We examined the effects of IL-18 on AP1 and NF-kappaB in Jurkat T cells in vitro. These effects were both time and dose dependent. Examination of transcription factor activation and IL-2 gene expression in Jurkat T cells revealed that sarcoid but not normal ELF activated AP1 and NF-kappaB, induced IL-2 gene transcription, and up-regulated IL-2 protein production. Addition of IL-18 to normal ELF also induced IL-2 mRNA accumulation, whereas correspondent depletion of IL-18 from sarcoid ELF using neutralizing Abs abrogated all of the effects. These data strongly implicate IL-18 in the pathogenesis of sarcoidosis via activation of AP1 and NF-kappaB, leading to enhanced IL-2 gene expression and IL-2 protein production and concomitant T cell activation.
- Published
- 2000
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