Early experience of a new national lung allocation scheme in the UK based on clinical urgency.

Introduction: A new UK Lung Allocation Scheme (UKLAS) was introduced in 2017, replacing the previous geographic allocation system. Patients are prioritised according to predefined clinical criteria into a three-tier system: the super-urgent lung allocation scheme (SULAS), the urgent lung allocation scheme (ULAS) and the non-urgent lung allocation scheme (NULAS). This study assessed the early impact of this scheme on waiting-list and post-transplant outcomes.

Elexacaftor/Tezacaftor/Ivacaftor as a Bridge to Lung Retransplant in a Recipient With Cystic Fibrosis.

The triple-combination cystic fibrosis transmembrane conductance regulator modulator elexacaftor/- tezacaftor/ivacaftor is known to improve lung function and have extrapulmonary benefits in people with cystic fibrosis. However, there is limited evidence for its use in patients with cystic fibrosis after lung transplant, where the donor lung expresses normal levels of the cystic fibrosis transmembrane conductance regulator. We describe the use of elexacaftor/tezacaftor/ivacaftor as a bridge to potential lung retransplant in a 37-year-old man with cystic fibrosis and chronic lung allograft dysfunction.

Management of ganciclovir resistance cytomegalovirus infection with CMV hyperimmune globulin and leflunomide in seven cardiothoracic transplant recipients and literature review.

Cytomegalovirus (CMV) disease caused by genetically resistant CMV poses a major challenge in solid organ transplant recipients, and the development of resistance is associated with increased morbidity and mortality. Antiviral resistance affects 5%-12% of patients following ganciclovir (GCV) therapy, but is more common in individuals with specific underlying risk factors. These include the CMV D+R- serostatus, type of transplanted organ, dose and duration of (Val)GCV ([V]GCV) prophylaxis, peak viral loads, and the intensity of immunosuppressive therapy.

Low Insertion Loss Plasmon-Enhanced Graphene All-Optical Modulator.

Graphene has emerged as an ultrafast optoelectronic material for all-optical modulators. However, because of its atomic thickness, it absorbs a limited amount of light. For that reason, graphene-based all-optical modulators suffer from either low modulation efficiencies or high switching energies.

Assessing the validity and applicability of the French 3-year prognostic score in the UK cystic fibrosis population - a national cohort study.

Models that predict outcomes, aid prognostication and inform the assessment of urgency for lung transplantation (LT) in CF are in demand. A prognostic score derived from the French adult CF registry to predict death or LT over 3-year follow-up was described in 2017 and validated using Canadian CF registry data. We assessed its performance in the UK CF population.

Lung clearance index in detection of post-transplant bronchiolitis obliterans syndrome.

Background: Long-term outcomes after lung transplantation are often limited by the development of obliterative bronchiolitis (OB), which is clinically defined using spirometry as bronchiolitis obliterans syndrome (BOS). Lung clearance index (LCI), derived from multiple breath washout (MBW) testing, is a global measure of ventilation heterogeneity that has previously been shown to be a more sensitive measure of obstructive small airway diseases than spirometry. We aimed to assess the feasibility of LCI in adult lung transplant patients and to compare LCI to BOS grade.

Management of Ganciclovir Resistant Cytomegalovirus Retinitis in a Solid Organ Transplant Recipient: A Review of Current Evidence and Treatment Approaches.

: Cytomegalovirus retinitis (CMVR) is a serious and potentially sight-threatening infection in immunocompromised individuals. Strategies for the management of drug-resistant CMVR are described. : A case of severe bilateral CMVR in a single lung transplant patient, with UL97 mutation conferring ganciclovir-resistance, is presented.

The renoprotective effect of concomitant fosfomycin in the treatment of pulmonary exacerbations in cystic fibrosis.

Background: Fosfomycin, effective in Cystic Fibrosis (CF), competes with aminoglycosides at renal binding sites and may therefore afford a renoprotective effect when used in combination therapy. We explored this by using markers of acute renal tubular damage [-acetyl-β-d-glucose-aminidase (NAG), alanine amino-peptidase (AAP) and β-microglobulin].

Methods: Using a prospective randomized crossover trial design, at an acute pulmonary exacerbation, 18 adult CF patients received either 14 days of intravenous (IV) tobramycin or IV tobramycin and IV fosfomycin, both in combination with a second IV antibiotic (colomycin).

The use of CMVIg rescue therapy in cardiothoracic transplantation: A single-center experience over 6 years (2011-2017).

Cytomegalovirus (CMV) is the most important infectious agent in solid organ transplant recipients and has a major impact on morbidity and mortality. Most cases are well managed with antiviral agents, but CMV hyperimmune globulin (CMVIg) can be used alongside antiviral therapy for prophylaxis in high-risk thoracic organ recipients and to treat life-threatening CMV infection or disease. CMVIg may also improve antiviral host defences when genetic resistance to antivirals or unwanted side effects occur.

Patient outcomes from time of listing for lung transplantation in the UK: are there disease-specific differences?

Background: The demand for lung transplantation vastly exceeds the availability of donor organs. This translates into long waiting times and high waiting list mortality. We set out to examine factors influencing patient outcomes from the time of listing for lung transplantation in the UK, examining for differences by patient characteristics, lung disease category and transplant centre.

Nebulized tobramycin in the treatment of adult CF pulmonary exacerbations.

Background: Repeated courses of intravenous (IV) aminoglycosides in cystic fibrosis (CF) patients are associated with cumulative nephrotoxicity. Targeting their delivery through the inhaled route during acute pulmonary exacerbations may also be effective, but without systemic side effects.

Methods: Using a randomized crossover trial design, in a pilot study we compared 14 days of IV tobramycin with nebulized tobramycin 300 mg twice a day (TNS) in acute respiratory exacerbations in 20 CF adults chronically infected with Pseudomonas aeruginosa (Psa).

Isolation of Aspergillus species from the airway of lung transplant recipients is associated with excess mortality.

Background: Aspergillus spp. are the leading cause of invasive fungal infection in lung transplant recipients. We investigated the relationship between the isolation of Aspergillus spp.

Segmental mediolytic arteriopathy with post-transplant lymphoproliferative disorder of the lung: case report and review of the literature.

Segmental mediolytic arteriopathy (SMA) is an extremely rare condition of uncertain etiology causing degeneration of arterial media, intramural dissection or the rupture of aneurysms. It is recognized as a rare cause of fatal intra-abdominal bleeding. We report the first case of recurrent intra-abdominal bleeding secondary to SMA in a lung transplant patient, with a further complication of lymphoproliferative disease in the transplanted lung.

Can a score derived from the Critical Care Minimum Data Set be used as a marker of organ dysfunction? - a pilot study.

Background: The aim of this study was to develop a simple organ score derived from the Critical Care Minimum Data Set (CCMDS) to compare with the Sequential Organ Failure Assessment (SOFA) score, a previously validated score of organ dysfunction.

Findings: The CCMDS collects data regarding the support of seven organ systems. To create a CCMDS derived score each level of organ support was allocated a numerical value.

Early experience with the Levitronix Centrimag device for extra-corporeal membrane oxygenation following lung transplantation.

Extra-corporeal membrane oxygenation (ECMO) is accepted as a salvage therapy to treat life-threatening complications following lung transplantation such as primary graft dysfunction, acute rejection or airway dehiscence. Levitronix Centrimag (Levitronix LLC, Waltham, MA) is a centrifugal pump that consists of a magnetically levitated bearing-less rotor designed to reduce blood friction. ECMO using the Levitronix Centrimag pump may be an ideal medium-term support for lung transplant recipients suffering these serious complications.

Extracorporeal membrane oxygenator as a bridge to successful surgical repair of bronchopleural fistula following bilateral sequential lung transplantation: a case report and review of literature.

Background: Lung transplantation (LTx) is widely accepted as a therapeutic option for end-stage respiratory failure in cystic fibrosis. However, airway complications remain a major cause of morbidity and mortality in these patients, serious airway complications like bronchopleural fistula (BPF) are rare, and their management is very difficult.

Case Presentation: A 47-year-old man with end-stage respiratory failure due to cystic fibrosis underwent bilateral sequential lung transplantation.

Comparison of methods of assessment of renal function in cystic fibrosis (CF) patients.

Renal failure is increasingly being recognised in CF patients, usually as a consequence of long-term nephrotoxic therapy. There is a need for a simple method of assessment of renal function in this patient group. We compared measured creatinine clearance from validated timed urine collections (the generally accepted practical test of glomerular filtration) with 10 formulae used to estimate creatinine clearance in a group of 74 CF adult patients and 29 matched normal controls.

Acute renal failure in CF patients chronically infected by the Liverpool epidemic Pseudomonas aeruginosa strain (LES).

Although acute renal failure has been described in children with CF in relation to intravenous aminoglycoside use, there are no reports in the adult CF literature. We describe 8 cases of acute renal failure in adult CF patients, all occurring during the use of intravenous aminoglycosides for the treatment of pulmonary exacerbations with an epidemic multi-resistant Pseudomonas aeruginosa strain. Potential contributory factors are discussed.

Renal impairment in cystic fibrosis patients due to repeated intravenous aminoglycoside use.

Although there are reports of cases of acute renal failure occurring in cystic fibrosis (CF) patients, usually in association with the use of nephrotoxic antibiotic therapy, there have been no studies of renal function in this patient group. We hypothesized that long-term use of intravenous (IV) nephrotoxic antibiotics (aminoglycosides and colistin sulphomethate) may contribute to renal disease in CF patients. In a prospective study, we assessed creatinine clearance as an index of renal function with two techniques (24-hr urine collections and the Cockroft-Gault formula) in a group of 80 stable adult CF outpatients chronically infected with Pseudomonas aeruginosa but with no history of preceding renal disease.

Increased morbidity associated with chronic infection by an epidemic Pseudomonas aeruginosa strain in CF patients.

Background: Chronic pulmonary infection with transmissible Pseudomonas aeruginosa strains in individuals with cystic fibrosis (CF) has been reported, raising issues of cross infection and patient segregation. The first such strain to be described (the Liverpool epidemic strain, LES) is now widespread in many UK CF centres. However, whether such infection carries a worse prognosis is unknown.

Sensitization of the mesoaccumbens dopamine response to nicotine.

This article reviews the evidence that pretreatment with nicotine causes a regionally selective sensitization of its stimulatory effects on a pathway, the mesoaccumbens dopamine (DA) system, which has been implicated in the locomotor stimulant response to nicotine and its ability to reinforce self-administration. The sensitization evoked by daily injections of nicotine is associated with a regionally selective downregulation of the control of mesoaccumbens DA neurons by inhibitory autoreceptors and depends upon co-stimulation of NMDA glutamatergic receptors. It is suggested that the sensitization is related to enhanced burst firing of mesoaccumbens neurons, which results in an enhancement of DA release into the extracellular space between the cells where it acts upon putative extrasynaptic dopamine receptors.