Unilateral Versus Bilateral Lung Transplantation: Do Different Esophageal Risk Factors Predict Chronic Allograft Failure?

GOALS: To assess the effect of unilateral versus bilateral lung transplantation (LTx) on esophageal motility and gastroesophageal reflux, and the association with the development of obstructive chronic lung allograft dysfunction (o-CLAD). BACKGROUND: We have shown that esophagogastric junction outflow obstruction, incomplete bolus transit, and proximal reflux are all independent risk factors for the development of chronic allograft failure. However, it remains unclear whether these factors are influenced by the type of surgery and how this relates to allograft failure. STUDY: Patients post-LTx (n=48, 24 female; aged 20 to 73 y) completed high-resolution impedance manometry and 24-hour pH/impedance. RESULTS: Patients who had undergone unilateral LTx were more likely to exhibit esophagogastric junction outflow obstruction (47% vs. 18%; P=0.046) and less likely to exhibit hypocontractility (0% vs. 21%; P=0.058) than those who had undergone bilateral LTx. Although the proportion of patients exhibiting gastroesophageal reflux was no different between groups (33% vs. 39%; P=0.505), those undergoing bilateral LTx were more likely to exhibit proximal reflux (8% vs. 37%; P=0.067). Univariate Cox proportion hazards regression analysis did not show a difference between unilateral versus bilateral LTx in the development of o-CLAD (hazard ratio=1.17; 95% confidence interval, 0.48-2.85; P=0.723). CONCLUSION: The type of LTx performed seems to lead to different risk factors for the development of o-CLAD. Physicians should be aware of these differences, as they may need to be taken into account when managing patient's post-LTx.

Tacrolimus dosage requirements in lung transplant recipients receiving antifungal prophylaxis with voriconazole followed by itraconazole: a preliminary prospective study.

BACKGROUND: Concomitant administration of the triazole antifungals, voriconazole or itraconazole, with tacrolimus can result in significant drug interaction in the transplant recipient. Limited published information exists regarding tacrolimus dosing when transitioning from voriconazole to itraconazole. The objective of this study was to evaluate the extent of the drug interaction with antifungal prophylaxis using voriconazole followed by a change to itraconazole in lung transplant recipients receiving tacrolimus. METHODS: This prospective study included lung transplant recipients receiving antifungal prophylaxis with voriconazole followed by a switch to itraconazole. Patients were followed from the time of transplant until two months after converting to itraconazole. All patients received standard immunosuppression with tacrolimus, mycophenolate mofetil, and a corticosteroid. Tacrolimus dose normalized concentrations using concentration/dose ratio were compared while receiving voriconazole versus itraconazole. RESULTS: Twenty lung transplant recipients were included in the final analysis. No difference was found with the tacrolimus dose normalized concentrations on voriconazole 254 ± 28 (ng/mL)/(mg/kg) compared with itraconazole 234 ± 34 (ng/mL)/(mg/kg), p = 0.65. CONCLUSION: Tacrolimus dosage adjustments were not necessary when converting from voriconazole to itraconazole. Validation in a larger population is needed to confirm these findings.

Noninvasive assessment of right heart function and hemodynamics during exercise in patients with pulmonary arterial hypertension.

OBJECTIVES: Noninvasive assessment of right heart function and hemodynamics in patients with pulmonary arterial hypertension (PAH) is most often performed at rest, whereas the symptoms, in general, present with exertion. Assessment during exertion is limited to symptom assessment and the 6-minute walk distance. We investigated the feasibility of obtaining echocardiographic data that could accurately reflect pulmonary artery pressures (PAP), particularly mean PAP and right ventricular function during exercise in patients with PAH. METHODS: We investigated right ventricular function and hemodynamics using echocardiography during symptom-limited exercise in 10 consecutive patients undergoing right heart catheterization (RHC) as part of their clinical evaluation for PAH. We further assessed these measurements for correlation with known predictors of outcome in PAH in an exploratory analysis. RESULTS: We were able to successfully obtain complete right heart measurements by echocardiography, including mean PAP, in the majority (9 of 10) of the subjects. One patient had an incomplete tricuspid regurgitation jet at rest and with exercise. Echocardiographic pulmonary vascular resistance correlated with RHC cardiac output and brain natriuretic peptide level, whereas tricuspid annular plane systolic excursion during exercise correlated with right atrial pressure on RHC, brain natriuretic peptide, and 6-minute walk distance. Tricuspid regurgitation velocity and mean PAP with exercise correlated moderately with mean PAP and cardiac output by RHC. CONCLUSIONS: Exercise echocardiography can provide meaningful data in patients with PAH, including measuring mean PAP. The presence of correlations in this small number of patients indicates promising targets for future investigation.

Eisenmenger Syndrome in Case of Extended Goldenhar Complex Treated With Heart-Lung Transplantation.

A patient diagnosed with expanded Goldenhar complex with oculoauriculovertebral spectrum complicated with complex pulmonary and congenital heart disease, underwent successful heart-lung transplantation 21 years ago, with excellent functional outcome and good quality of life. Heart-lung transplantation can be an option of care for patients with expanded Goldenhar complex. (Level of Difficulty: Advanced.).

Remote ex vivo lung perfusion at a centralized evaluation facility.

BACKGROUND: In the US, only 23% of lungs offered for transplantation are transplanted. Ex vivo lung perfusion (EVLP) allows for evaluation of additional donor lungs; its adoption has been limited by resources and expertise. Dedicated facilities with a centralized lung evaluation system (CLES) could expand access to EVLP. METHODS: In this unblinded, nonrandomized, traditional feasibility study, 7 US transplant centers referred lungs declined for standard transplantation to a dedicated EVLP facility, which utilized a CLES. EVLP was remotely monitored by the transplant teams. CLES lungs were matched with contemporaneous conventional static cold-preserved controls at each center. RESULTS: A total of 115 recipients were enrolled, and 66 received allografts from 63 donors after EVLP at the dedicated CLES facility. Forty-nine contemporaneous patients served as controls. Primary graft dysfunction grade 3 at 72 hours (PGD3-72 hours) was higher in the CLES group with 16 (24%) vs 2 (4%) in the control (common RD 95% CI, 0.07-0.32; p = 0.0009). All recipients survived to 30 days and 1-year survival was similar for both groups (92% controls vs 89% CLES; common RD 95% CI, -0.14-0.08; p = 0.58). Total preservation time, hospital and ICU lengths of stay, and time to first extubation were longer in the CLES group. CONCLUSIONS: Remote ex vivo perfusion of lung allografts declined for conventional transplantation at a dedicated CLES facility is feasible and resulted in additional transplants. Recipients of allografts assessed with a CLES had a higher rate of PGD3-72 hours, but similar 30-day and 1-year outcomes compared to conventional lung recipients. (NCT02234128).

Effects of administration of intravenous naloxone on gas exchange in brain-dead lung donors.

OBJECTIVE: To observe the effect of naloxone on the lung function of potential lung transplant donors with neurogenic pulmonary edema. DESIGN AND INTERVENTIONS: Donors aged 16 to 55 years without any factors to contraindicate lung donation (pneumonia, pulmonary contusion, etc) were included. Ventilator settings were standardized to a tidal volume of 10 to 12 mL/kg, an FIO2 of 0.40, and a respiratory rate that kept PCO2 between 35 and 45 mm Hg. Chest physiotherapy, nebulizer treatments, and frequent suctioning were undertaken. Baseline arterial blood gas analysis and an oxygen challenge were performed. The patients were then given 8 to 10 mg of naloxone. Oxygen challenges and arterial blood gas analyses were repeated every 4 to 6 hours. The data were analyzed by using a paired t test, and each patient served as his or her own control. SETTING: These interventions were performed on the 19 LifeQuest donors who met the set criteria from July 2002 to July 2004. RESULTS: The PaO2 on the oxygen challenge immediately after administration of naloxone increased from 329 (SD 177) to 363 (SD 191) mm Hg, although the increase from baseline was not significant. The PaO2 from the second oxygen challenge (median time, 7 hours after administration of naloxone) increased to 413 (SD 177) mm Hg (P<.01).

Diagnosis of Acute Cellular Rejection Using Probe-based Confocal Laser Endomicroscopy in Lung Transplant Recipients: A Prospective, Multicenter Trial.

BACKGROUND: Acute cellular rejection (ACR) in lung transplant recipients requires demonstration of perivascular lymphocytic infiltration in alveolar tissue samples from transbronchial biopsies (TBBs). Probe-based confocal laser endomicroscopy (pCLE) allows in vivo observation of alveolar, vascular, and cellular microstructures in the lung with potential to identify ACR. The objective of our prospective, blinded, multicenter observational study was to identify pCLE findings in patients with ACR diagnosed histopathologically by TBB. METHODS: Lung transplant recipients undergoing diagnostic bronchoscopies within 1 year posttransplant for suspected ACR had pCLE video imaging obtained immediately prior to tissue sampling via TBB. Findings of 2 pCLE criteria, abundant alveolar cellularity and perivascular cellularity (PVC), were assessed by 4 investigators familiar with pCLE and compared with histopathologic criteria of ACR to derive sensitivity, specificity, area under the receiver operating characteristic curve, and accuracy. Interobserver agreement was assessed by calculating intraclass coefficient and Fleiss κ. Findings were analyzed before and after a consensus meeting of investigators on interpreting images. RESULTS: Thirty pCLE procedures were performed on 24 patients, 8 showing ACR in TBB. Diagnostic performance and interobserver agreement using pCLE to identify PVC were significantly higher than those of abundant alveolar cellularity (P < 0.01). The number of blood vessels identified with PVC on pCLE was significantly correlated with histopathologic activity grading of ACR (P < 0.01). Perivascular cellularity agreement among investigators significantly improved after consensus meeting (P < 0.01). CONCLUSIONS: When found on pCLE, PVC is a feasible and reproducible criterion for assessment of ACR in vivo, but there is a learning curve for image interpretation.

Utilization and Cost Analysis of Lung Transplantation and Survival After 10 Years of Adapting the Lung Allocation Score.

BACKGROUND: Lungs are allocated in the United States using the lung allocation score (LAS). We investigated the effect of LAS trends on lung transplant-related costs, healthcare utilization, and mortality. METHODS: Utilization data from Mayo Clinic (Florida and Minnesota) from 2005 to 2015 were obtained from the electronic health records (N = 465). Costs were categorized as 1-year posttransplant or transplant episode and standardized using 2015 Medicare reimbursement and cost-to-charge ratios. Regression analysis was used to assess the relationship of LAS to length of stay (LOS), mortality, and cost of transplant. RESULTS: The mean LAS at transplant increased from 45.7 to 58.3 during the study period, whereas the 1-year survival improved from 88.1% to 92.5% (P < 0.0001). The proportion of patients transplanted with LAS of 60 or greater increased from 16.9% to 33.3%. Posttransplant, overall, and intensive care unit LOS increased with increasing LAS. Patients with higher LAS had substantially higher transplant episode costs. An increase of LAS at transplant by 10 points increased inflation-adjusted costs by 12.0% (95% confidence interval, 9.3%-14.5%). CONCLUSIONS: The mean LAS at transplant has significantly increased over time associated with increases in LOS, resource utilization and cost. Lung allocation score has not jeopardized overall survival, but a high LAS (>60) at transplant is associated with increased mortality.

Intervenções terapêuticas com cavalos: uma ferramenta para o bem-estar dos estudantes? / Therapeutic interventions with horses: a tool for student well-being?

Resumo: Introdução: A literatura sobre educação médica vem mostrando que os alunos de Medicina vivenciam dificuldades quanto à sobrecarga de atividades e tarefas, culminando com estresse e depressão, muitas vezes associados aos desafios trazidos pelo modelo pedagógico da Aprendizagem Baseada em Problemas. Objetivo: Este estudo teve como objetivo relatar os resultados de duas intervenções terapêuticas desenvolvidas com estudantes, tendo como foco situações-problema enfrentadas no curso de Medicina e como finalidade a promoção do bem-estar. Método: Trata-se de pesquisa de natureza qualitativa e exploratória. Criou-se um cenário para vivências psicodramáticas com cavalos. A amostra foi composta por duas discentes de Medicina, que atenderam ao critério de inclusão "participar do Centro Acadêmico". As alunas atuaram como protagonistas-pacientes-participantes. As intervenções com cada participante foram individuais e agiram nos níveis intrapsíquico e sistêmico, considerando aqui o sistema educação médica. Além da dramatização em si no palco-arena, ocorreram entrevistas semidirigidas abertas, à guisa de aquecimento e compartilhamento dos resultados, no dia da intervenção e seis meses após. Resultado: As protagonistas-pacientes-participantes, provenientes de dois cursos diferentes, ambos com currículo organizado em Aprendizagem Baseada em Problemas, cursavam o sexto e oitavo semestres do curso. Os "dramas-sofrimento em relação ao curso" escolhidos para serem trabalhados foram "competição na tutoria" e "sobrecarga". A dramatização trouxe à tona tomada de consciência do seu protagonismo em relação ao problema e da possibilidade de aquisição de novas respostas espontâneo-criativas, o que foi verificado seis meses após, por meio do relato das protagonistas-pacientes-participantes. O trabalho terapêutico realizado proporcionou às discentes melhora no bem-estar e melhor desempenho nas atividades estudantis, pessoais e sociais, de modo a prepará-las a ser as profissionais mais humanizadas que o SUS busca. Conclusão: Os resultados sugerem que o uso das "intervenções terapêuticas com cavalos" pode auxiliar as escolas médicas no cumprimento das DCN, pela via da promoção da saúde dos discentes de Medicina.

Abstract: Introduction: The literature on medical education has been revealing that medical students experience difficulties with the overload of activities and tasks, culminating in stress and depression, often associated with the challenges brought by the Problem-Based Learning pedagogical model. Objective: to report the results of two therapeutic interventions developed with students, focusing on problem situations faced in the medical course and with the purpose of promoting well-being. Method: Qualitative and exploratory research. A scenario was created for psychodramatic experiences with horses. The convenience sample consisted of two medical students, who met the inclusion criterion 'participate in the Academic Center' of the course. They acted as protagonist-patient-participants. The interventions with each participant were individual, and acted at the intrapsychic and systemic levels, considering here the medical education system. Besides the dramatization itself on the stage-arena, there were open semi-structured interviews, as a warm-up and sharing of results, on the day of the intervention and six months later. Results: The protagonist-patient-participants are female, from two different universities which both offer a curriculum centered on Problem-Based Learning, and were in the 6th and 8th semesters of the course. The 'suffering-dramas in relation to the course' chosen by each protagonist-patient-participant were 'tutoring competition' and 'overload'. The dramatization was effective in promoting awareness of its protagonism in relation to the problem and the possibility of acquiring new spontaneous-creative responses, which was verified six months later, in the protagonist-patient-participants' report. The therapeutic work promoted improved student well-being and performance in academic, personal and social activities, preparing the students to be the most humanized professionals, as sought by the SUS. Conclusion: The results suggest that the use of "Therapeutic Intervention with Horses" can help medical schools to comply with National Curriculum Guidelines, through health promotion among medicine students.

Feasibility, Safety, and Tolerance of Mesenchymal Stem Cell Therapy for Obstructive Chronic Lung Allograft Dysfunction.

Feasibility, tolerance, and safety of intravenous infusions of allogeneic mesenchymal stem cell (MSC) therapy in lung transplant recipients with bronchiolitis obliterans syndrome (BOS) are not well established. MSCs were manufactured, cryopreserved, transported to our facility, thawed, and infused into nine recipients with moderate BOS (average drop in forced expiratory volume in 1 second was 56.8% ± 3.2% from post-transplant peak) who were refractory to standard therapy and not candidates for retransplant. Cells were viable and sterile prior to infusion. Patients received a single infusion of either 1 (n = 3), 2 (n = 3), or 4 (n = 3) million MSCs per kg. Patients were medically evaluated before; during; and at 24 hours, 1 week, and 1 month after infusion for evidence of infusion-related adverse events and tolerance of therapy. Vital signs, pulmonary function test results, Borg Dyspnea Index, and routine laboratory data were recorded. Vital signs and O2 saturation did not significantly change during or up to 2 hours after MSC infusion. There were no significant changes in gas exchange variables, pulmonary function test results, or laboratory values at 1, 7, and 30 days postinfusion compared with preinfusion values. Infusion of MSCs in patients with BOS was feasible, safe, and well tolerated and did not produce any significant adverse changes in clinical, functional, or laboratory variables during or up to 30 days after infusion. Manufacturing, transport, and administration of intravenous, allogeneic bone marrow-derived MSCs in doses from 1 to 4 million MSCs per kg is safe in lung transplant recipients with BOS. Stem Cells Translational Medicine 2018;7:161-167.

In situ analysis of mTORC1/2 and cellular metabolism-related proteins in human Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare progressive cystic lung disease with features of a low-grade neoplasm. It is primarily caused by mutations in TSC1 or TSC2 genes. Sirolimus, an inhibitor of mTOR complex 1 (mTORC1), slows down disease progression in some, but not all patients. Hitherto, other potential therapeutic targets such as mTOR complex 2 (mTORC2) and various metabolic pathways have not been investigated in human LAM tissues. The aim of this study was to assess activities of mTORC1, mTORC2 and various metabolic pathways in human LAM tissues through analysis of protein expression. Immunohistochemical analysis of p-S6 (mTORC1 downstream protein), Rictor (mTORC2 scaffold protein) as well as GLUT1, GAPDH, ATPB, GLS, MCT1, ACSS2 and CPT1A (metabolic pathway markers) were performed on lung tissue from 11 patients with sporadic LAM. Immunoreactivity was assessed in LAM cells with bronchial smooth muscle cells as controls. Expression of p-S6, Rictor, GAPDH, GLS, MCT1, ACSS2 and CPT1A was significantly higher in LAM cells than in bronchial smooth muscle cells (P<.01). No significant differences were found between LAM cells and normal bronchial smooth muscle cells in GLUT1 and ATPB expression. The results are uniquely derived from human tissue and indicate that, in addition to mTORC1, mTORC2 may also play an important role in the pathobiology of LAM. Furthermore, glutaminolysis, acetate utilization and fatty acid ß-oxidation appear to be the preferred bioenergetic pathways in LAM cells. mTORC2 and these preferred bioenergetic pathways appear worthy of further study as they may represent possible therapeutic targets in the treatment of LAM.

Safety of percutaneous dilatational tracheostomy with direct bronchoscopic guidance for solid organ allograft recipients.

OBJECTIVE: To determine the safety of percutaneous dilatational tracheostomy (PDT) for solid organ allograft recipients, who have increased risks of bleeding and infection. PARTICIPANTS AND METHODS: We reviewed the records of patients who underwent solid organ transplant between January 1, 2001, and September 30, 2005, followed by PDT (using the Ciaglia technique) with direct bronchoscopic guidance. We recorded comorbid conditions, number of days from intubation and transplant, positive end-expiratory pressures, ratios of PaO2 to fraction of inspired oxygen, coagulation study findings, complications, and procedure-related mortality rates. RESULTS: Of the 51 patients in our study, 17 had undergone lung transplant; 32, liver transplant; and 2, kidney transplant. The median age was 55 years (range, 27-73), and 53% of patients were men. The median time from intubation to PDT was 10 days and from transplant to PDT, 22 days. The median ratio of PaO2 to fraction of inspired oxygen was 293, and the median positive end-expiratory pressure was 5 cm H2O. Twenty-one patients were receiving dialysis, and 11 were recovering from sepsis (of these, 8 were receiving vasopressors). Ten had coagulopathies (none of which were associated with bleeding complications). Complications were infrequent (7 periprocedural, 4 postprocedural) and included bleeding, bradycardia, hypotension, tracheal ring fracture, and cannula malfunction. Of the bleeding complications, only 2 were clinically remarkable and required removal of the tracheostomy or surgical revision. No infectious complications or procedure-related deaths were noted. CONCLUSION: Percutaneous dilatational tracheostomy was tolerated well in recipients of solid organ allografts and had a relatively low risk of major complications and a low procedure-related mortality rate. This method should be considered an acceptable alternative to surgical tracheostomy.

Retrospective study of pulmonary function tests in patients presenting with isolated reduction in single-breath diffusion capacity: implications for the diagnosis of combined obstructive and restrictive lung disease.

OBJECTIVE: To examine the frequency and spectrum of diseases associated with isolated reduction in the diffusing capacity of lung for carbon monoxide (D(Lco)). PATIENTS AND METHODS: We retrospectively identified all potentially dyspneic patients who had pulmonary function tests (PFTs) performed at the Mayo Clinic in Jacksonville, Fla, between January 1, 1990, and June 30, 2000, that showed reduced D(Lco) (< 70% of predicted), normal lung volumes (total lung capacity and residual volume > 80% and < 120% of predicted, respectively), and airflow variables (forced expiratory volume in 1 second and forced vital capacity values > 80% of predicted and forced expiratory volume in 1 second/forced vital capacity ratio > 70% of predicted). Only patients who had also undergone chest computed tomography (CT) and echocardiography within 1 month of PFTs were studied. RESULTS: Of the 38,095 patients who underwent PFTs during the study period, 179 (0.47%; 95% confidence interval [CI], 0.40%-0.54%) had isolated D(Lco) abnormalities. The 27 patients (15.1%; 95% CI, 10.2%-21.2%) who had also undergone chest CT and echocardiography within 1 month of PFTs form the study cohort reported herein. Their mean D(Lco) was 50% +/- 15% (95% CI, 45%-56%) with average normal pulse oxygen saturation at rest and mild hypoxemia with activity. Thirteen of the 27 patients (48%; 95% CI, 28.7%-68.1%) had underlying emphysema evident on CT. Eleven of these 13 patients had emphysema associated with a restrictive lung process. The 14 patients without emphysema had interstitial lung disease, pulmonary vascular disease, and other isolated findings. Six patients with combined emphysema and idiopathic pulmonary fibrosis accounted for the largest percentage (22%) of patients with Isolated D(Lco) reduction. The mean +/- SD smoking history of the 27 patients in the study cohort was 36 +/- 33 pack-years (range, 0-116 pack-years). CONCLUSION: Dyspneic patients with respiratory symptoms and normal lung volumes and airflows associated with Isolated reduction in D(Lco) should be evaluated for underlying diseases such as emphysema, with or without a concomitant restrictive process, and pulmonary vascular disease.

Impaired Esophageal Motility and Clearance Post-Lung Transplant: Risk For Chronic Allograft Failure.

OBJECTIVES: Gastroesophageal reflux is common in patients post-lung transplantation (LTx) and thus considered a risk factor for aspiration and consequently allograft rejection and the development of chronic allograft failure. However, evidence supporting this remains unclear and often contradictory. Our aim was to examine the role played by esophageal motility on gastroesophageal reflux exposure, along with its clearance and that of boluses swallowed, and the relationship to development of obstructive chronic lung allograft dysfunction (o-CLAD). METHODS: Patients post-LTx (n=50, 26 female; mean age 55 years (range, 20-73 years)) completed high-resolution impedance manometry and 24-h pH/impedance. Esophageal motility abnormalities were classified based upon the Chicago Classification version 3.0. RESULTS: Esophagogastric junction outflow obstruction alone (EGJOOa) (P=0.01), incomplete bolus transit (IBT) (P=0.006) and proximal reflux (P=0.042) increased the risk for o-CLAD. Patients with EGJOOa were most likely to present with o-CLAD (77%); despite being less likely to exhibit abnormal numbers of reflux events (10%) compared with those with normal motility (o-CLAD: 29%, P<0.05; abnormal reflux events: 64%, P<0.05). Patients with EGJOOa had lower total reflux bolus exposure time than those with normal motility (0.6 vs. 1.5%; P<0.05). In addition, poor esophageal clearance documented by abnormal post-reflux swallow-induced peristaltic wave index associated with o-CLAD; inversely correlating with the proportion of reflux events reaching the proximal esophagus (r=-0.251; P=0.052). CONCLUSIONS: These observations support esophageal dysmotility, especially EGJOOa, and impaired clearance of swallowed bolus or refluxed contents, more so than just the presence of gastroesophageal reflux alone, as important risk factors in the development of o-CLAD.

Giant cell interstitial pneumonia in patients without hard metal exposure: analysis of 3 cases and review of the literature.

Giant cell interstitial pneumonia is a rare lung disease and is considered pathognomonic for hard metal lung disease, although some cases with no apparent hard metal (tungsten carbide cobalt) exposure have been reported. We aimed to explore the association between giant cell interstitial pneumonia and hard metal exposure. Surgical pathology files from 2001 to 2004 were searched for explanted lungs with the histopathologic diagnosis of giant cell interstitial pneumonia, and we reviewed the associated clinical histories. Mass spectrometry, energy-dispersive x-ray analysis, and human leukocyte antigen typing data were evaluated. Of the 455 lung transplants, 3 met the histologic criteria for giant cell interstitial pneumonia. Patient 1 was a 36-year-old firefighter, patient 2 was a 58-year-old welder, and patient 3 was a 45-year-old environmental inspector. None reported exposure to hard metal or cobalt dust. Patients 1 and 2 received double lung transplants; patient 3 received a left single-lung transplant. Histologically, giant cell interstitial pneumonia presented as chronic interstitial pneumonia with fibrosis, alveolar macrophage accumulation, and multinucleated giant cells of both alveolar macrophage and type 2 cell origin. Energy-dispersive x-ray analysis revealed no cobalt or tungsten particles in samples from the explanted lungs. None of the samples had detectable tungsten levels, and only patient 2 had elevated cobalt levels. The lack of appropriate inhalation history and negative analytical findings in the tissue from 2 of the 3 patients suggests that giant cell interstitial pneumonia is not limited to individuals with hard metal exposure, and other environmental factors may elicit the same histologic reaction.

An overview of immunosuppression in solid organ transplantation.

Significant advancements in solid organ transplantation immunosuppressive medications and regimens have resulted in improved outcomes over the years. A multidrug approach involving medications with different mechanisms of action is commonly used. Induction therapy can involve the use of antibody agents or higher doses of medications used for maintenance therapy. A calcineurin inhibitor, an antiproliferative agent, and a corticosteroid commonly serve as the initial triple medication regimen. Due to the potential for nephrotoxicity with the use of calcineurin inhibitors and chronic conditions with the prolonged use of corticosteroids, various withdrawal strategies are used in practice. Antimicrobial agents are prescribed to provide prophylaxis against certain viral, fungal, and bacterial infections. Other concomitant medications in the regimens for patients who have undergone transplantation vary depending on patient-specific factors and conditions.

Weight loss prior to lung transplantation is associated with improved survival.

BACKGROUND: Obesity is associated with increased mortality after lung transplantation and is a relative contraindication to transplant. It is unknown whether weight reduction prior to transplantation ameliorates this risk. Our objective was to determine whether weight loss prior to lung transplantation improves survival. METHODS: Our investigation was a two-center, retrospective cohort study of lung transplant recipients between January 1, 2000 and November 5, 2010. Change in weight, demographics, transplant details, lung allocation score, length of intensive care and mechanical ventilator days and graft and patient survival were abstracted. Wilcoxon's signed-rank test and the Cox proportional hazard model were used for analysis where appropriate. RESULTS: Three hundred fifty-five patients (55% male, median age 59 years) satisfied inclusion and exclusion criteria. After adjusting for standard demographic and clinical measures, a 1-unit reduction in BMI pre-transplant was associated with a reduced risk of death with a hazard ratio 0.89 (95% confidence interval 0.82 to 0.96; p = 0.004). This survival benefit persisted in the group with baseline BMI ≥ 25 kg/m(2) (overweight and obese) and hazard ratio 0.85 (95% CI 0.77 to 0.95; p = 0.003), but not in those with a BMI ≤ 24.9 kg/m(2). The 1-unit reduction in BMI was also associated with a 6.1% decrease in median mechanical ventilator days (p = 0.02) and a trend toward decreased intensive care unit length of stay (p = 0.06). CONCLUSIONS: A reduction in BMI prior to lung transplantation was associated with a reduction in the risk of death and mechanical ventilator days. A greater reduction in BMI was associated with a greater survival benefit.

Mayo clinic experience of lung transplantation in pulmonary lymphangioleiomyomatosis.

OBJECTIVES: Lymphangioleiomyomatosis (LAM) is a rare, cystic lung disease that generally results in progressive decline in lung function. Despite advancement of pharmacological therapy for LAM, lung transplantation remains an important option for women with end-stage LAM. METHODS: Patients with LAM undergoing lung transplantation at the Mayo Clinic campuses in Rochester, Minnesota and Jacksonville, Florida since 1995 were retrospectively reviewed. RESULTS: Overall, 12 women underwent lung transplantation. Nine of 12 (75%) underwent double lung transplant. The mean age was 42 ± 8 years at the time of transplant. One patient (8%) had a chylothorax and 7 (58%) had recurrent pneumothoraces, 4 (33%) of which required pleurodesis. All had diffuse, cystic lung disease on chest CT consistent with LAM which was confirmed in the explant of all patients. The average length of ICU and hospital stays were 5 ± 4 and 19 ± 19 days, respectively. Mild to moderate anastomotic ischemia was evident in all patients but resolved with time. No patient was treated with sirolimus pre-transplant. Seven patients received sirolimus post-transplant; however, clinical benefit was documented in only 2 patients, 1 of which was treated for large retroperitoneal cysts with ureteral obstruction and another with persistent chylothorax and retroperitoneal lymphangioleimyomas. Five patients are deceased. The median survival by Kaplan-Meier analysis was 119 months with a median follow-up of 68 months (range 2-225 months). CONCLUSIONS: Lung transplant remains a viable treatment for patients with end-stage LAM. The role of sirolimus peri-transplantation remains ill-defined.

Traumatic bronchial rupture and platypnea-orthodeoxia.

A patient with blunt trauma and traumatic bronchial rupture and lung collapse had prominent symptoms of platypnea-orthodeoxia syndrome. These symptoms were relieved by bronchial repair. The syndrome is rarely seen and is usually associated with a patent foramen ovale or atrial septal defect. The syndrome has not been described previously in association with traumatic bronchial rupture.