Increased risk of PTLD in lung transplant recipients with cystic fibrosis

Background

Post-transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following lung transplantation. Recipients with cystic fibrosis (CF) may have an increased risk of PTLD although the literature is limited to single center cohorts. Our primary aim is to examine PTLD in an adult lung transplant population by utilizing the International Society for Heart and Lung Transplantation Registry.

Post-transplant diabetes mellitus in lung transplant recipients: incidence and risk factors

Objective: Post-transplant diabetes mellitus (PTDM) is a common and potentially serious complication after solid organ transplantation. There are only a few data, however, about the incidence of DM in patients undergoing lung transplantation. Patients and methods: The medical records of 119 consecutive patients who underwent lung transplantation from 1998 to September 2004 were reviewed. Patients were divided in three groups according to their diabetes status, including pre-transplant DM, the PTDM group and those without DM. Patient records and all laboratory data were reviewed and the clinical course of diabetes was monitored. All recipients were treated with tacrolimus based regimen. Results: Mean follow-up for all patients was 25 ± 10. Twenty-three patients had DM in the pre-lung transplantation (LTX) DM group. PTDM developed in 34 of the remaining 96 patients (35.4%) with an incidence of 20%, 23% after 6 months and 12 months post-transplant. No significant difference was noted between 12 and 24 months post-LTX. The patients who developed DM were older (57 ± 15 vs 53 ± 13 years, p = 0.009), had increased BMI (26 ± 5 vs 24 ± 4, p = 0.0001), shorter time from diagnosis to LTX (21 ± 13 vs 28 ± 18 months, p = 0.007) more cytomegalovirus infection and more acute rejection and hyperglycemia in the first month after LTX. Four patients died in the PTDM group compared to nine patients in the no-DM group (12% vs 14%; p = 0.72). Conclusions: Post-transplant diabetes is a common complication in lung transplant patients receiving tacrolimus-based immunosuppression. The risk for developing PTDM is greatest among older recipients, those obese, and among recipients with more rejections episodes.     

Combined lung-liver-pancreas transplantation in a recipient with cystic fibrosis

Cystic fibrosis (CF) affects multiple organs including the lung, liver, and pancreas. Lung transplant, liver transplant, and combined lung-liver transplant have become well-established therapies for CF patients with end-stage organ failure. Thus far, however, there has been limited experience with pancreas transplantation in CF. In this report, we detail the clinical history, transplant procedure, and post-operative recovery of a patient who underwent combined lung-liver-pancreas transplant for advanced CF.     

Pulmonary exacerbations and acute declines in lung function in patients with cystic fibrosis

Background

Patients with cystic fibrosis (CF) who experience acute declines in percent predicted FEV₁ (ppFEV₁ decreased ≥10% relative to baseline) are often not treated with antibiotics for pulmonary exacerbations (PEx), whereas other patients are treated even when they have not experienced a decline in lung function.

Long-term outcome of lung transplantation for cystic fibrosis — Danish results

Objective: Over the last decades improvements in medical therapies have delayed the progression of lung disease in cystic fibrosis (CF). However, lung disease is still the most common cause of premature death, and lung transplantation today is the only treatment for end-stage lung disease in patients with CF. We present a retrospective review of the outcome of CF patients transplanted in Denmark since start of the national lung transplantation programme in 1992. Methods: In a 10-year period, 47 patients with CF were listed for lung transplantation; 29 patients underwent transplantation and 18 patients died while waiting for donor organs. Eleven patients received en block double lung transplantation with direct bronchial artery revascularization and 18 patients received bilateral sequential lung transplantation. Median age at transplantation was 29 years (range 11–50). Results: The perioperative mortality (≤30 days) was 3.5% (1/29 patients). Actuarial survival of transplanted patients at 1, 3, 5 and 8 years was 89, 80, 80 and 70%, respectively. Actuarial survival of non-transplanted patients on the waiting list at 1 and 2 years was 28 and 11% (P<0.0001). Causes of death of transplanted patients were: respiratory failure on day 7 (n=1), bronchiolitis obliterans syndrome (n=2), infection (Cytomegalovirus, Aspergillus fumigatus) (n=2), bronchial anastomosis dehiscence (n=1). Pulmonary function (FEV₁% predicted) improved from median 20% (range 13–31) pre-transplant to 71% (range 19–118) after 5 years (P<0.0001). Renal function (⁵¹Cr-EDTA clearance) decreased from median 97 ml/min (range 45–190) pre-transplant to 32 ml/min (range 8–84) 6 months after transplantation (P<0.001). Three patients (11%) received dialysis post-transplant of whom two underwent kidney transplantation. Immunosuppressive induction therapy with rabbit-antithymocyte-globulin compared to daclizumab resulted in fewer treatments for acute rejection within the first 3 months post-transplant (P=0.05 at 5–8 weeks). Burkholderia multivorans was present in three patients pre-transplant with satisfying long-term outcome in one patient. Conclusions: Lung transplantation is a well-established life-extending treatment for patients with CF and end-stage lung disease. The operative mortality is low and CF patients have a significant early survival benefit after lung transplantation. Satisfying long-term results can be achieved in this young and severely ill group of patients.     

Enhanced cyclosporine-itraconazole interaction with cola in lung transplant recipients

BACKGROUND: Invasive aspergillosis is a major cause of morbidity and mortality in lung transplant recipients (LTR), occurring in up to 15% of patients post-transplant. The 14% aspergillus incidence at the Cleveland Clinic Foundation prompted institution of universal prophylaxis with oral itraconazole (ICZ) in 1997. We report our experience with two protocols of ICZ administration in non-cystic fibrosis LTR and the interaction with cyclosporine (CSA). METHODS: Group 1 patients (n=12) were administered ICZ capsules in a fasting or fed state, with or without a histamine-2 (H-2) receptor antagonist or proton pump inhibitor. Group 2 patients (n=12) received the same protocol as group I, but in a fed state with a carbonated beverage (cola) to increase acidity in the stomach to enhance absorption of ICZ. The ICZ dose was 200 mg/d, given as one daily dose. A historical control group (n=10) did not receive chemoprophylaxis with ICZ. CSA daily doses, dose intervals, concentration, cost, and random ICZ levels were documented over a 4-month period of time and compared using generalized estimating equations. RESULTS: The daily CSA mg/kg/d dose decreased over time in all three groups, but no differences were found between the three groups. The CSA dosing interval over time was significantly prolonged in group 2 compared to group 1 or the control group (p< or =0.003). Over time, there was no difference in CSA concentration between all groups. There was no difference in cost over time between the three groups; however, the mean cost of CSA therapy was significantly lower in group 2 compared to the control group (p=0.025). Group 2 administered ICZ with cola had greater random blood concentrations of ICZ (p=0.019). CONCLUSIONS: ICZ capsules administered in a fed state with a cola resulted in greater random levels of ICZ, a decrease in cost/d of CSA, and a prolongation of CSA dosing interval. Although daily CSA dosage trended lower in group 2, it did not reach statistical significance. We believe these changes in CSA dosing over time reflect increased absorption of ICZ and recommend verifying ICZ absorption with an itraconazole level, especially when CSA intervals are not prolonged.     

Introducing the need for lung transplantation in children with cystic fibrosis: Parental experiences

Lung transplantation (LTx) is the only treatment available for adult and pediatric end-stage lung disease secondary to cystic fibrosis (CF). The timing of introducing LTx has significant medical and psychological implications for the child and the family. This study explored the views and recommendations of parents of children with CF, who had been asked to consider LTx and referred to a national transplant centre. Parents participated in a telephone-based, semi-structured interview. Responses were analysed using Content Analysis. Parental recommendations and the emergent protocol are discussed, together with implications for clinical practice.     

Capecitabine for skin cancer prevention in solid organ transplant recipients

Skin cancers are the most common malignancies in solid organ transplant recipients (SOTR). A case-observational, retrospective study was performed to determine the efficacy of low-dose capecitabine in the secondary prevention of skin cancers in SOTRs treated at a single institution. SOTRs with recurrent squamous cell carcinoma (SCC) and/or basal cell carcinoma (BCC) were given low-dose capecitabine 1 g/m(2) daily, days 1-14 of a 21-d treatment cycle. Skin surveillance was performed by dermatologists every 1-3 months. Cumulative incidence rates of SCC, BCC, and actinic keratosis (AK) before and after treatment were scored and statistically compared for each patient using a non-parametric Wilcoxon signed rank test. Fifteen patients (13 men and two women) with a median age of 57 yr (range 40-73) were treated. Incidence rates as measured by mean number of events per month declined by 0.33 for SCC, 0.04 for BCC, and 2.45 for AK (p < 0.05). The most common grade 3 and 4 toxicities included fatigue (40.0%), hand-foot syndrome (20.0%), and diarrhea (20.0%). The discontinuation rate at one yr was approximately 33.3%. We conclude that oral capecitabine significantly decreases the incidence rates of recurrent SCC, BCC, and AK in SOTRs and is associated with manageable toxicity.     

Peri-operative cardiac morbidity in kidney transplant recipients: incidence and risk factors

BACKGROUND: Renal transplant recipients are known to be at increased risk for developing cardiac disease. In both general and peripheral vascular surgery, pre-operative risk stratification (and intervention when indicated) has decreased the incidence of peri-operative cardiac complications. In this study, we set out to identify subsets of patients at high risk for peri-operative cardiac complications after a renal transplant. METHODS: We retrospectively reviewed the records of 2694 adult renal transplants performed at the University of Minnesota between January 1, 1985 and December 31, 1998. We determined the incidence of peri-operative (within 30 d post-transplant) cardiac complications, including myocardial infarction (MI). Risk factors for the development of these complications were determined by multivariate analysis. RESULTS: We found 163 peri-operative cardiac complications, for an overall incidence of 6.1%. Specific cardiac complications included MI (n=43, 1.6%), arrhythmia (n=74, 2.7%), angina (n=31, 1.2%), cardiac arrest (n=13, 0.5%), and congestive heart failure (n= 2, 0.1%). By multivariate analysis, significant risk factors for any cardiac complication were age> or =50 yr (relative risk (RR)=3.0, p=0.0001) and pre-transplant cardiac disease (RR=3.3, p=0.0001). Not significant were diabetes mellitus (DM), cadaver donor source, pre-transplant dialysis, a history of smoking, and hypertension. Significant risk factors for peri-operative MI were age> or =50 yr, pre-existing cardiac disease, and DM. Diabetic patients with pre-existing cardiac disease were at especially high risk for peri-operative cardiac events. CONCLUSIONS: Patients>50 yr and those with pre-existing cardiac disease, especially if diabetic, are at significantly increased risk for developing peri-operative cardiac complications after a renal transplant. Such patients require aggressive pre-operative investigations, which may include coronary angiography, to decrease the risk of post-transplant complications.     

Discrepancies between clinical and autopsy diagnoses in lung transplant recipients

Akindipe OA, Fernandez‐Bussy S, Staples ED, Baz MA. Discrepancies between clinical and autopsy diagnoses in lung transplant recipients.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01144.x.
© 2009 John Wiley & Sons A/S. Abstract: We sought to investigate the role of autopsy diagnoses in lung transplantation by comparing the clinically derived cause of death with autopsy deduced cause of death in a cohort of lung transplant recipients. We retrospectively reviewed all consecutive autopsy findings on lung transplant recipients transplanted between March 1994 and March 2007. We reviewed medical records and our lung transplant database to determine the clinical diagnosis of cause of death based on the clinical assessment and discharge summary at the time of death. Our study showed that 21% of the autopsies performed on lung transplant recipients at our institution revealed findings unsuspected at the time of death. Myocardial infarction, pulmonary embolism, high grade acute cellular rejection and infections were the most frequently missed diagnoses. The autopsy remains a useful tool in confirming diagnostic accuracy in lung transplant recipients.     

An analysis of potential risk factors for early complications from fiberoptic bronchoscopy in lung transplant recipients

Several reviews exist describing the safety of bronchoscopy in lung transplant recipients. However, the incidence of bronchoscopic complications in lung transplant recipients in relation to trainee involvement, and clinical characteristics such as pre‐transplant diagnosis and transplant type, has not been described. We performed a retrospective cohort study of all lung transplant recipients undergoing flexible fiberoptic bronchoscopy (n = 259) at the University of California, San Francisco, between January, 2003, and June, 2009. Complications included bleeding, pneumothorax, aspiration, oversedation, and hypoxemia. From 2003 to 2009, 3734 flexible fiberoptic bronchoscopies were performed, including 2111 (57%) with transbronchial biopsies. Trainees were involved in 2102 bronchoscopies (56%), including 1046 transbronchial biopsies (49.5%). Complications occurred in 27 bronchoscopies [0.7% (95% Confidence Interval [CI]: 0.4–1.0)], with 10 involving a trainee (37%). Twenty (74%) occurred during bronchoscopies with transbronchial biopsies. Six of these involved a trainee, while 14 involved an attending alone (P = 0.03). We did not find differences in pre‐transplant diagnosis, transplant type, lung, or renal function between subjects who suffered a complication and those who did not (P ≥ 0.30). The involvement of trainees, pre‐transplant diagnosis, and transplant type do not significantly impact the rate of bronchoscopic complications in lung transplant recipients.     

Rural barriers to early lung cancer detection: Exploring access to lung cancer screening programs in New Hampshire and Vermont

BackgroundRural populations face many health disadvantages compared to urban areas. There is a critical need to better understand the current lung cancer screening landscape in these communities to identify targeted areas to improve the impact of this proven tool.MethodsData from the County Health Rankings of New Hampshire and Vermont was reviewed for population density, distribution of adult smokers, and level of education compared to the distribution of Lung Cancer Screening Facilities throughout these two states.ResultsScreening programs in southern counties of Vermont with lower levels of education have decreased access. In New Hampshire, there are no programs within 30 miles of the areas with the largest distribution of smokers, and decreased access in some areas with the lowest levels of education.ConclusionsImproving equitable access to high-quality screening services in rural regions and the creation of targeted interventions to address decreased access in areas of high tobacco use and low education is vital to decreasing the incidence of latestage presentations of lung cancer within these populations.     

Renal transplant outcome in high-cardiovascular risk recipients

BACKGROUND: Cardiovascular (CV) disease is the foremost cause of mortality and an important cause of morbidity in renal transplant recipients. The disease burden is likely to increase as older patients are accepted for transplantation. The outcome of these high-CV risk patients after renal transplantation, especially with known pre-transplant coronary artery disease (CAD), has not been studied. Hence, we looked at the CV outcome in patients with known pre-transplant CAD. METHODS: All renal transplants performed between 1998 and 2002 at our center, followed up to 2005, were divided into high- and low-risk groups, based on the presence of one or more of the following: pre-transplant angina, myocardial infarction, and positive coronary angiogram. The two groups were compared for post-transplant cardiac events and patient and graft survival. The factors predictive of post-transplant cardiac events were also determined by Cox-regression multivariate analysis. RESULTS: Forty-five patients (10.5%), out of 429, had post-transplant cardiac events; 31.3% in the high risk, and 6.5% in the low-risk group (p = 0.001). Five-yr patient survival was lower in the high-risk group (82.8% vs. 93.1%, p = 0.004), while five-yr overall graft survival and death censored graft survival were statistically not different (74.8% vs. 84.1%, p = 0.08 and 87.3% vs. 90%, p = 0.25). Forty-one percent of patients who were treated with angioplasty plus stenting or bypass graft prior to transplantation had post-transplant cardiac events, as compared with 28% of those without intervention in the high-risk group and 6.5% of patients in the low-risk group (p = 0.001). Age, pre-transplant cardiac disease, arrhythmias, and low-ejection fraction (< or = 40%) were significant independent predictors of post-transplant cardiac events. CONCLUSION: Post-transplant survival of high-CV risk patients (with known CAD) is lower than that of low-risk recipients but remains acceptable. Cardiac interventions may reduce perioperative risk but do not reduce the probability of post-transplant cardiac events to that of low-risk group.     

Simultaneous fundoplication and gastric stimulation in a lung transplant recipient with gastroparesis and reflux

BACKGROUND: Gastroparesis following lung transplantation can complicate medical management leading to malnutrition, weight loss, and erratic absorption of immunosuppressive medications, which are all important factors in the success of grafts. Gastric electrical stimulation has been shown to reduce the frequency of nausea and vomiting and lead to weight gain in patients with gastroparesis refractory to standard medical treatment; however, it has not yet been reported as being used for the treatment of gastroparesis in lung transplant recipients. METHODS: We report the case of a female bilateral lung transplant recipient suffering from severe gastric reflux and severe gastroparesis, who was successfully treated with simultaneous creation of a laparoscopic Nissen fundoplication and placement of a gastric stimulator. RESULTS: The patient noted an immediate and sustained decrease in her symptoms of nausea and vomiting, and an increased appetite, and less variability in the serum levels of her immunosuppressive medication. CONCLUSION: Lung transplant recipients with severe gastroparesis and reflux may benefit from Nissen fundoplication and gastric electrical stimulation.     

Hyperhomocysteinemia and transplant coronary artery disease in cardiac transplant recipients

BACKGROUND: In cardiac transplant recipients, long-term survival may be limited by transplant coronary artery disease (TxCAD). Hyperhomocysteinemia (Hhcy) has been associated with vascular disease and is common in transplant recipients. The objective of this study was to determine the relationship between fasting homocysteine (Hcy) concentrations and TxCAD in a cohort of cardiac transplant recipients. METHODS: Forty-eight patients more than 5 yr after transplant were recruited from a cohort of 72 consecutive patients with in-depth analysis of homocysteine levels from the Cardiac Transplant Clinic. Early morning fasting blood was obtained, and the plasma separated and frozen within 30 min. Hcy concentrations were determined by high-performance liquid chromatography (HPLC) with pulsed integrated amperometry. Coronary angiograms were reviewed in a blinded fashion. TxCAD was diagnosed, using the most recent angiogram, when a >25% lesion was present anywhere in the coronary tree. RESULTS: Forty-eight patients transplanted between 1985 and 1994 were studied. The mean Hcy concentration for the cohort was 23.5+/-5.0 micromol/L, all patients had homocysteine levels above the upper range of normal (5-15 micromol/L). Hcy concentrations were significantly higher in patients with angiographic evidence of TxCAD: 25.0+/-5.9 vs. 21.9+/-3.4 micromol/L, p=0.03. This effect persisted when covariates were taken into account using logistic regression analysis. CONCLUSIONS: Hhcy is associated with TxCAD. Prospective studies are required to confirm this association and to assess the efficacy of Hcy-lowering therapy in this patient population.     

Cumulative radiation dose after lung transplantation in patients with cystic fibrosis

Purpose

The purpose of this study was first to evaluate the imaging-related cumulative post-transplantation radiation dose in cystic fibrosis (CF) lung transplantation (LT) recipients and second, to identify the occurrence and type of malignancies observed after LT.

Clostridium difficile carriage in adult cystic fibrosis (CF); implications for patients with CF and the potential for transmission of nosocomial infection

Clostridium difficile is an anaerobic Gram-positive, spore-forming, toxin-producing bacillus transmitted among humans through the faecal–oral route. Despite increasing carriage rates and the presence of C. difficile toxin in stool, patients with CF rarely appear to develop typical manifestations of C. difficile infection (CDI). In this study, we examined the carriage, toxin production, ribotype distribution and antibiotic susceptibility of C. difficile in a cohort of 60 adult patients with CF who were pre-lung transplant. C. difficile was detected in 50% (30/60) of patients with CF by culturing for the bacteria. C. difficile toxin was detected in 63% (19/30) of C. difficile-positive stool samples. All toxin-positive stool samples contained toxigenic C. difficile strains harbouring toxin genes, tcdA and tcdB. Despite the presence of C. difficile and its toxin in patient stool, no acute gastrointestinal symptoms were reported. Ribotyping of C. difficile strains revealed 16 distinct ribotypes (RT), 11 of which are known to be disease-causing including the hyper-virulent RT078. Additionally, strains RT002, RT014, and RT015, which are common in non-CF nosocomial infection were described. All strains were susceptible to vancomycin, metronidazole, fusidic acid and rifampicin. No correlation was observed between carriage of C. difficile or any characteristics of isolated strains and any recorded clinical parameters or treatment received. We demonstrate a high prevalence of hypervirulent, toxigenic strains of C. difficile in asymptomatic patients with CF. This highlights the potential role of asymptomatic patients with CF in nosocomial transmission of C. difficile.