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Background Combined multivisceral transplantation has emerged as a therapeutic option for a select patient cohort; however, clinical decision-making remains complex and controversial. The aim of this study was to examine patient characteristics, operative complications, and long-term outcomes of all patients who have undergone combined heart-lung-liver transplantation (HLLTx) in Australia. Methods In this study, we performed a retrospective analysis of all adult patients who have undergone combined HLLTx in Australia to date. Recipient clinical characteristics, waitlist, and transplant outcomes are described. Results Eight adult patients have received HLLTx at a single Australian transplant center. Recipients of HLLTx have typically been young (median age, 30.1 years; range, 24-37), underweight (median body mass index, 19.8 kg/m2; range, 16.2-30.4) patients with cystic fibrosis (n = 8, 100%) with severe airflow obstruction (median forced expiratory volume in the first second of expiration, 24% predicted; range, 17%-48%) accompanied by liver cirrhosis confirmed on histopathology (n = 8, 100%). Despite relative preservation of synthetic function and low model for end-stage liver disease scores (median, 8; range, 6-17), all recipients had complications of portal hypertension prior to transplantation, with many patients having suffered life-threatening variceal hemorrhage. In this cohort, HLLTx was associated with overall posttransplant survival of 87.5% at 30 days, 71.4% at 1 year, and 42.9% at 5 years. Listing for combined HLLTx was associated with prolonged waitlist times relative to bilateral sequential single-lung transplantation (median 556 vs 56 days, respectively), however waitlist mortality and/or delisting was comparable between groups. Conclusions Taken together, these findings highlight the opportunities and challenges facing combined (heart-) lung and liver transplantation in patients with multiorgan failure.

BACKGROUND: This study aimed to examine intermediate-term outcomes of lung transplantation (LTx) recipients from donors after circulatory death (DCD).METHODS: We examined the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry data for patients transplanted between January 2003 and June 2017 at 22 centers in North America, Europe, and Australia participating in the DCD Registry. The distribution of continuous variables was summarized as median and interquartile range (IQR) values. Wilcoxon rank sum test was used to compare distribution of continuous variables and chi-square or Fisher's exact test for categorical variables. Kaplan-Meier survival rates after LTx from January 2003 to June 2016 were compared between DCD-III (Maastricht category III withdrawal of life-sustaining therapy [WLST]) only and donors after brain death (DBD) using the log-rank test. Risk factors for 5-year mortality were investigated using Cox multivariate proportional-hazards model.RESULTS: The study cohort included 11,516 lung transplants, of which 1,090 (9.5%) were DCD lung transplants with complete data. DCD-III comprised 94.1% of the DCD cohort. Among the participating centers, the proportion of DCD-LTx performed each year increased from 0.6% in 2003 to 13.5% in 2016. DCD donor management included extubation in 91%, intravenous heparin in 53% and pre-transplant normothermic ex vivo donor lung perfusion in 15%. The median time interval from WLST to cardiac arrest was 15 minutes (IQR: 11-22 minutes) and to cold flush 32 minutes (IQR: 26-41minutes). Compared with DBD, donor age was higher in DCD-III donors (46 years [IQR: 34-55] vs 40 years [IQR: 24-52]), bilateral LTx was performed more often (88.3% vs 76.6%), and more recipients had chronic obstructive pulmonary disease and emphysema as their transplant indication. Five-year survival rates were comparable (63% vs 61%, p = 0.72). In multivariable analysis, recipient and donor ages, indication diagnosis, procedure type (single vs bilateral and double LTx), and transplant era (2003-2009 vs 2010-2016) were independently associated with survival (p CONCLUSION: This ISHLT DCD Registry report with 5-year follow-up demonstrated similar favorable long-term survival in DCD-III and DBD lung donor recipients at 22 experienced centers globally. These data indicate that more extensive use of DCD-LTx would increase donor organ availability and may reduce waiting list mortality. (C) 2019 International Society for Heart and Lung Transplantation. All rights reserved.

This paper explores the spatial and embodied effects of Islamophobia in Paris by focusing on victims' use and adoption of specific strategies in order to avert potential situations of discrimination. We draw upon thirty-three qualitative interviews highlighting the main victims of Islamophobia – young women who wear a headscarf – and present an analysis of their spatial strategies. First, experiences of oppression restrict and limit mobility as veiled women avoid spaces in central, privileged and crowded districts especially when they are alone or with their children. Instead, they use familiar places where they feel comfortable and welcome (such as their neighbourhood or community restaurants and cafes). Second, experiences of oppression have also changed the embodied strategies of veiled women who either feel the need to be strong and integrated, or more discreet and less visible, especially through their clothes. Finally, veiled Muslim women reinvent new mobility and embodied practices in response to geopolitical events; these activist strategies highlight the sophisticated responses of Muslim women in the context of feminist geopolitics and politicisation of their religious faith. This paper hereby contributes to the political and feminist geographies of Muslim women and their multiple negotiations of ‘Muslimness’ in response to anti-Muslim acts.

Background: Oral pirfenidone reduces lung function decline and mortality in idiopathic pulmonary fibrosis (IPF). Systemic exposure can have significant side effects including nausea, rash, photosensitivity, weight loss, and fatigue. Dosage reductions in response to side effects may be suboptimal in slowing the rate of disease progression. This trial (ATLAS) assessed the safety, tolerability, and efficacy of pirfenidone solution for inhalation (AP01) in patients with IPF. Methods: This phase 1b randomized, open-label, dose-response trial is being performed at 25 sites in six countries (ANZCTR: ACTRN12618001838202). Patients diagnosed with IPF within 5 years, forced vital capacity (FVC) 40–90% predicted, and intolerant, unwilling, or ineligible for oral pirfenidone or nintedanib were randomly assigned 1:1 to nebulized AP01 50 mg once daily (QD) or 100 mg twice daily (BID) for 48 weeks. The primary efficacy measure was absolute change in FVC % predicted. Findings: Participants were recruited between May 31, 2019, and April 30, 2020; of 141 IPF patients screened, 91 were enrolled (50 mg QD: n=46, 100 mg BID: n=45). Changes in FVC % predicted (95% CI) over 48 weeks, estimated as slopes, were −­5·3 (−8·0, −2·7) in the 50 mg QD and −0·5 (−3·3, 2·3) in the 100 mg BID groups (evaluable n=39 and 34, respectively); difference was 4·8 (1·0, 8·7); p=0·0152. The most common treatment-related adverse events (all mild to moderate) included cough (14, 15·4%), rash (11, 12·1%), nausea (8, 8·8%), throat irritation (5, 5·5%), dysgeusia and fatigue (4 each, 4·4%), and dizziness and dyspnoea (3 each, 3·3%). Interpretation: Mean FVC % predicted was stable in the 100 mg BID group, and FVC response was significantly better than in the 50 mg QD group. Nausea and rash side effects commonly associated with oral pirfenidone were less frequent with AP01. Further study of AP01 is warranted. Trial Registration: This phase 1b randomized, open-label, dose-response trial is being performed at 25 sites in six countries (ANZCTR: ACTRN12618001838202). Funding: Avalyn Pharma Declaration of Interest: MLS, DN, LF, KO, and ABM are all employees of the sponsor, Avalyn Pharma. Authors AGW, AB, MLWilsher, PH, MS, and WP report no conflicts of interest. NC received a grant from Boehringer Ingelheim and consulting fees from Boehringer Ingelheim, Carrick, Carrick, Redex, UCB, and Novartis; speaker fees and travel sponsorship from Boehringer Ingelheim and Roche; and payment for participation on data safety monitoring/advisory board from Boehringer Ingelheim. IG reports consulting fees from Amplia, Ad Alta, and Accendatech; speaking fees from Boehringer Ingelheim; and payment for participation in a safety review committee from Accendatech. TJC reports receiving grants/contracts from Boehringer Ingelheim, Roche, Bristol Myers Squibb, Biogen, Galapagos, and Avalyn Pharma; speaker’s honoraria from Boehringer Ingelheim and Roche; and payment for participation on data safety monitoring/advisory board from Boehringer Ingelheim, Roche, Bristol Myers Squibb, and Promedior. EJ received honoraria for lectures from Boehringer Ingelheim, Roche, AstraZeneca, MDS, Chiesi; sponsored travel to meetings from Boehringer Ingelheim and Roche; and payment for participation in advisory boards from Boehringer Ingelheim, Roche, AstraZeneca, Novartis, MDS, Berlin-Chemie, and Chiesi. MWijsenbeek reports payments to her institution from Boehringer Ingelheim, Roche, the Netherlands Organisation for Health Research and Development, the Dutch Lung Foundation, the Dutch Pulmonary Fibrosis Patient Association, the Thorax Foundation, ErasmusMC, and Sarcoidoisis.nl. Consulting fees were paid to her institution by Boehringer Ingelheim, Roche, Galapagos, Bristol Myers Squibb, Galecto, and Respivant; honoraria were paid to her institution by Boehringer Ingelheim, Roche, and Novartis. MWijsenbeek received sponsored travel from Boehringer Ingelheim and Roche, and her institution received payment for her participation in data safety monitoring/advisory board from Savara and Galapagos. CG received consulting fees from Avalyn Pharma. GR reports receiving support from Avalyn Pharma for consulting and for chairing the Data Safety Monitoring Board during the conduct of the study; personal and consulting fees from Boehringer Ingelheim, Respivant, and Roche; grants from the NIH; and consulting fees from Bellerophon Therapeutics, Biogen, Bristol Myers Squibb, Fibrogen, Nitto, Promedior, Respivant, and Veracyte. Ethical Approval: The trial was approved by local ethics committees, and all patients provided written informed consent before trial entry.

Purpose Gastroparesis (GP) affects 23-91% lung transplant (LT) recipients and may be associated with increased gastro-oesophageal reflux disease (GORD), an established risk factor for Chronic Lung Allograft Dysfunction (CLAD). The temporal association between GP, CLAD and GORD remains unclear. This study assessed whether patients with GP post LT experienced more GORD, CLAD and inferior nutrition-related outcomes. Methods Single centre retrospective review of adult LT recipients between January 2015 and December 2018 was conducted. GP was identified by either abnormal Gastric emptying studies (GES) or significant food residue retained within the stomach on upper endoscopy. GES were performed on patients symptomatic for gastroparesis - bloating, early satiety, nausea. Reflux was diagnosed via routine performance of 24-hour pH studies on all patients irrespective of symptoms, from 3 months post LT. Outcome variables included demographics, diagnosis of CLAD, survival at 3, 12 months, surgery duration, fundoplication pre and post LT, presence of GORD and weight trajectory post LT. Presence of GP was compared to the above variables. Results 149 patients were analysed; 27.5% (n=41) had GP, diagnosed through GE study (n=33), or Endoscopy (n=8). There was no association between GP and GORD (p=0.265), CLAD (p=0.529), 3-month (p=0.621), or 12-month (p=0.645) survival. GP was associated with an increased BMI, both as a continuous and categorical variable (BMI: 25.0 SD 4.6 vs 23.3 SD 3.9 kg/m2, p=0.030), and patients with GP were more likely to have unintentional weight loss at 6 weeks (GP: -6.2 ± 5.7%, 95% CI -4.4 to -8.1 vs. no GP: -1.7 ± 5.8%, 95% CI -3 to -0.56; p Conclusion Patients with gastroparesis post LT did not have worse short-term survival, GORD or CLAD outcomes. They were, however, more likely to experience unintentional weight loss. Intensive Dietetic input post LT is required in patients identified with GP to prevent malnutrition.

Objective Lung transplantation is associated with high rates of bleeding and frequent blood transfusion. The authors aimed to determine if point-of-care coagulation testing (POCCT) reduced transfusion requirements. Design, Settings, and Participants A before-and-after cohort analysis conducted at a single tertiary referral center. Ninety-three sequential adult patients between January 2010 and January 2014 undergoing isolated lung transplant without preoperative extracorporeal support were analyzed. Intervention ROTEM and multi-plate POCCT were introduced on July 1, 2012, with an associated algorithm based on the results. Measurements and Main Results Statistically significant decreases in the proportion of patients receiving PRBCs (87% v 65%; p = 0.015), FFP (72% v 30%; p v 37%; p = 0.002) were found after the intervention. There were small decreases in median chest tube blood loss at 2 hours (300 mLs v 215 mLs; p = 0.03) and 4 hours (440 mLs v 350 mLs; p = 0.050) but not at 12 hours postoperatively. There were no changes in reoperation for bleeding (9% v 4%; p = 0.158) or in-hospital mortality (6% v 2%; p = 0.617). The cost of blood products administered decreased from a median of $3,935.00 to $991.00 (p Conclusions Use of POCCT in lung-transplant surgery is associated with significant reductions in blood product use and cost. There were no detectable changes in outcome aside from a small decrease in early postoperative bleeding.

Purpose Calculation of estimated energy requirements (EER) is critical in achieving nutritional targets in pre-lung transplantation (LT) candidates. This study compared bedside prediction of EER using simple equations with a more complex technology based EER using a multisensor device (Sensewear v8.1, SW). SW estimated energy requirements was then compared to estimated energy intake (EEI) at pre-LT assessment. Methods Single institution retrospective cross-sectional observational study of adult patients assessed for LT between Oct 2016 and Apr 2019. Patients wore the SW device on their left tricep for a minimum of 3 days. Patients with poor compliance, Results 117 patients were included. 55% male, mean age 51.8 ±13.8years, BMI 25.1±4.5kg/m2. 4 patients were assessed as underweight, 53 healthy weight, 44 overweight and 17 obese. 17% of patients were assessed as malnourished (SGA-B, mild-moderately malnourished). Respiratory disease: CF (15%), COPD (41%), IPF (31%), other (13%). Food record data existed for 82% of candidates (n=96). There was strong agreement between all predictive equations and SW. Schofield had the strongest correlation (0.836, p Conclusion Whilst all EER equations correlated well with SW as the reference standard, Schofield had the strongest agreement with SW, while larger variations were observed with other equations (over/underestimation) which may be clinically relevant for some patients. EER predictive energy equations provide a simple, rapid and accurate assessment of nutritional requirements in pre-lung transplantation.

Purpose While physical activity level (PAL) is an important functional measure in people with chronic respiratory disease, little is known about PAL post lung transplantation (LTx). Aim: To compare PAL pre- and post-LTx and determine the relationship between changes in PAL and demographic (age), lung function (FEV1%) and exercise capacity measures. Methods Using a prospective observational design, participants were assessed pre- and 12 months post-LTx. PAL was defined as total energy expenditure in twenty-four hours/basal metabolic rate. PAL, mean minutes/day being physically active (1.69 metabolic equivalents (METs) or greater), and mean minutes/day performing moderate activity (3.0 METs or greater) were measured using the SenseWear multi-sensor device. Age, FEV1%, six-minute walk distance (6MWD), and quadriceps strength corrected for body weight (QS%) were assessed. Results 67 participants (40 males; 29 COPD, 15 idiopathic pulmonary fibrosis, 12 cystic fibrosis, 11 other), mean (SD) age 50.7 ± 12.4 years were included. Mean FEV1% increased by 52.6 ± 32.1% (p=0.001) and 6MWD increased by 174 ± 128m (p=0.001) 12 months after transplant, but QS% did not improve (-2.0 ± 21.0%, p=0.437). Mean PAL at 12 months (1.49 ± 0.23) had significantly improved compared to pre-LTx (1.40 ± 0.29, p=0.028). However, 17 (25.4%) participants remained extremely inactive (PAL below 1.4) and 37 (55.2%) participants were sedentary (PAL 1.4 to 1.69). Mean time physically active increased by 32 ± 130 minutes/day (p=0.045) but time performing moderate activity remained unchanged (p=0.062). Post-LTx, PAL was correlated with 6MWD (r=0.58, p=0.001), QS% (r=0.47, p=0.001) and age (r=-0.24, p=0.050) but not FEV1% (p=0.575). ∆PAL was correlated with ∆6MWD (r=0.37, p=0.002) but not with ∆QS% (p=0.090), age (p=0.716), or ∆FEV1% (p=0.875). Conclusion Most recipients remain physically inactive 12 months after lung transplantation despite significant improvements in lung function and exercise capacity. Age, exercise capacity and quadriceps strength appear important determinants of post-transplant PAL. However, there were only modest increases in physical activity post-transplantation.

The increased skin cancer incidence in organ transplant recipients is well-known, but the skin cancer burden at any one time is unknown. Our objective was to estimate the period prevalence of untreated skin malignancy and actinic keratoses in high-risk kidney and liver transplant recipients and to assess associated factors. Organ transplant recipients underwent full skin examinations by dermatologically trained physicians. The proportion of examined organ transplant recipients with histopathologically confirmed skin cancer in the 3-month baseline period was estimated. Prevalence ratios with 95% confidence intervals indicated significant associations. Of 495 high-risk organ transplant recipients (average age = 54 years, time immunosuppressed = 8.9 years), 135 (27%) had basal cell carcinoma, squamous cell carcinoma or Bowen's disease (intraepidermal carcinoma) present and confirmed in the baseline period, with respective prevalence proportions of 10%, 11%, and 18% in kidney transplant recipients and 10%, 9%, and 13% in liver transplant recipients. Over 80% had actinic keratosis present, with approximately 30% having 5 or more actinic keratoses. Organ transplant recipients with the highest skin cancer burden were Australian born, were fair skinned (prevalence ratio = 1.61, 95% confidence interval = [1.07, 2.43]), reported past skin cancer (prevalence ratio =3.39, 95% confidence interval = [1.93, 5.95]), and were receiving the most frequent skin checks (prevalence ratio = 1.76, 95% confidence interval = [1.15, 2.70]). In conclusion, high-risk organ transplant recipients carry a substantial measurable skin cancer burden at any given time and require frequent review through easily accessible, specialized services.

Shahid Husain, MD, MS, Amparo Sole, MD, PhD, Barbara D. Alexander, MD, MHS, Saima Aslam, MD, MS, Robin Avery, MD, Christian Benden, MD, Eliane M. Billaud, PharmD, PhD, Daniel Chambers, MBBS, MD, Lara Danziger-Isakov, MD, Savitri Fedson, MD, Kate Gould, MD, Aric Gregson, MD, Paolo Grossi, MD, PhD, Denis Hadjiliadis, MD, Peter Hopkins, MD, Me-Linh Luong, MD, Debbie J.E. Marriott, MD, Victor Monforte, MD, Patricia Munoz, MD, PhD, Alessandro C. Pasqualotto, MD, PhD, Antonio Roman, MD, Fernanda P. Silveira, MD, Jeffrey Teuteberg, MD, MS, Stephen Weigt, MD, Aimee K. Zaas, MD, MHS, Andreas Zuckerman, MD, and Orla Morrissey, MD, PhD

Lung volume reduction of emphysematous lobes results in clinical improvement for patients with severe emphysema. However, some segments within a lobe are often substantially more diseased than others, thereby warranting a more targeted approach of the emphysematous parts of a lobe. We therefore did a study to assess whether or not selective sequential treatment of the more diseased upper lobe segments with bronchoscopic vapour ablation led to clinical improvement.For the multicentre, parallel-group, randomised, controlled, open-label Sequential Staged Treatment of Emphysema with Upper Lobe Predominance (STEP-UP) trial, adult patients aged 45-75 years with severe, upper lobe-predominant emphysema with a forced expiratory volume in 1 s (FEV1) between 20% and 45%, substantial hyperinflation, and post-rehabilitation 6-min walk test (6MWT) greater than 140 m were enrolled from 13 hospital sites in Europe (ten sites) and Australia (three sites). A computer-generated blocked randomisation scheme (block size three per site based on a random table from an independent biostatistician) stratified by site was used to randomly assign enrolled patients 2:1 to segmental vapour ablation (treatment group) or standard medical management (control group). Patients and investigators were not masked to group assignment. The primary efficacy endpoints were statistically significant changes in FEV1 and St George's Respiratory Questionnaire (SGRQ-C) scores between trial groups at 6 months, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01719263.Between June 30, 2013, and Oct 1, 2014, 134 patients were screened and 70 were enrolled and randomly assigned: 46 to the treatment group and 24 to the control group. One patient in the treatment group did not receive treatment because of physician decision post-randomisation; this patient is excluded from all analyses. The mean relative improvement in FEV1 between the treatment group versus the control group was 14·7% (95% CI 7·8-21·5%; p0·0001) and in SGRQ-C was -9·7 points (95% CI -15·7 to -3·7; p=0·0021). COPD exacerbation was the most common serious adverse event, occurring in 11 (24%) of 45 patients in the treatment group and one (4%) of 24 in the control group. One exacerbation resulted in a patient death 84 days after treatment; this was judged by the data and safety monitoring board to be possibly related to treatment. No pneumothorax occurred within 30 days of treatment.Compared with standard medical management, targeted thermal vapour ablation of more diseased segments and preservation of less diseased segments resulted in clinically meaningful and statistically significant improvements in lung function and quality of life at 6 months, with an acceptable safety profile.Uptake Medical.

Purpose Gram -ve bacteria have recently been found to induce O-antigen-specific IgG2 and IgA ‘inhibitory’ antibodies (iAb) in the host which are not only impotent but block complement-mediated killing. Our group has demonstrated the clinical benefit of plasmapheresis in patients infected with Pseudomonas aeruginosa (Psa) strains which have deployed this virulence factor. Here we assessed the prevalence and clinical impact of iAb in a large lung transplant cohort. Methods Our centre maintains a biobank of sera from the majority of recipients. Recipients with at least one archival serum sample from the first post-transplant year were included. Presence of iAb in sera was determined by measuring titre of IgG2 and IgA against the three most prevalent (∼80% coverage) local Psa serotypes. Presence of iAb was confirmed by serum-bactericidal assays against serotype matched Psa. Results 123 recipients (54(44%) female; aged 54yrs (range 19-70); 38(31%) cystic fibrosis (CF), 89(72%) Psa colonised; median follow-up 33 (19.3-70.6) months) with 425 archived sera were studied. 25% of the whole cohort and 47% of CF subjects had iAb. iAb were persistent in subjects with multiple sera. The demographic factors independently associated with iAb were CF (OR 4.52, 95% CI 1.83-11.23, p 0.001) and younger age (OR 0.95, 95% CI 0.92-0.98, p 0.002); however, Psa-colonisation, gender, transplant type, CMV status, induction agent use and follow-up time were unassociated. In those with iAb, CLAD-free and overall survival was inferior in all (overall, CF, Psa-colonised) cohorts (Figure 1). iAb and CMV mismatch status but not Psa-colonisation status, were independently associated with inferior CLAD free survival and overall survival. Conclusion iAb are prevalent after lung transplantation, in part explain the known association between Psa-colonisation and CLAD, and independently predict poor outcomes. Development of strategies to counter iAb could significantly improve outcomes in patients with Gram -ve infection.

Erratic tacrolimus blood levels are associated with liver and kidney graft failure. We hypothesized that erratic tacrolimus exposure would similarly compromise lung transplant outcomes. This study assessed the effect of tacrolimus mean and standard deviation (SD) levels on the risk of chronic lung allograft dysfunction (CLAD) and death after lung transplantation.We retrospectively reviewed 110 lung transplant recipients who received tacrolimus-based immunosuppression. Cox proportional hazard modeling was used to investigate the effect of tacrolimus mean and SD levels on survival and CLAD. At census, 48 patients (44%) had developed CLAD and 37 (34%) had died.Tacrolimus SD was highest for the first 6 post-transplant months (median, 4.01; interquartile range [IQR], 3.04-4.98 months) before stabilizing at 2.84 μg/liter (IQR, 2.16-4.13 μg/liter) between 6 and 12 months. The SD then remained the same (median, 2.85; IQR, 2.00-3.77 μg/liter) between 12 and 24 months. A high mean tacrolimus level 6 to 12 months post-transplant independently reduced the risk of CLAD (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.63-0.86; p0.001) but not death (HR, 0.96; 95% CI, 0.83-1.12; p = 0.65). In contrast, a high tacrolimus SD between 6 and 12 months independently increased the risk of CLAD (HR, 1.46; 95% CI, 1.23-1.73; p0.001) and death (HR, 1.27; 95% CI, 1.08-1.51; p = 0.005).Erratic tacrolimus levels are a risk factor for poor lung transplant outcomes. Identifying and modifying factors that contribute to this variability may significantly improve outcomes.

BACKGROUND: The objective of this study was to review the international experience in lung transplantation using lung donation after circulatory death (DCD).METHODS: In this retrospective study, data from the International Society for Heart and Lung Transplantation (ISHLT) DCD Registry were analyzed. The study cohort included DCD lung transplants performed between January 2003 and June 2013, and reported to the ISHLT DCD Registry as of April 2014. The participating institutions included 10 centers in North America, Europe and Australia. The control group was a cohort of lung recipients transplanted using brain-dead donors (DBDs) during the same study period. The primary end-point was survival after lung transplantation.RESULTS: There were 306 transplants performed using DCD donors and 3,992 transplants using DBD donors during the study period. Of the DCD transplants, 94.8% were Maastricht Category whereas 4% were Category IV and 1.2% Category V (euthanasia). Heparin was given in 54% of the cases, donor extubation occurred in 90% of the cases, and normothermic ex vivo lung perfusion (EVLP) was used in 12%. The median time from withdrawal of life support therapy (WLST) to cardiac arrest was 15 minutes (5th to 95th percentiles of 5 to 55 minutes), and from WLST to cold flush was 33 minutes (5th to 95th percentiles of 19.5 to 79.5 minutes). Recipient age and medical diagnosis were similar in DCD and DBD groups (p = not significant ENS]). Median hospital length of stay was 18 days in DCD lung transplants and 16 days in DBD transplants (p = 0.016). Thirty-day survival was 96% in the DCD group and 97% in the DBD group. One-year survival was 89% in the DCD group and 88% in the DBD group (p = NS). Five-year survival was 61% in both groups (p = NS). The mechanism of donor death within the DCD group seemed to influence recipient early survival. The survival rates through 30 days were significantly different by donor mechanism of death (p = 0.0152). There was no significant correlation between the interval of WLST to pulmonary flush with survival (p = 0.11).CONCLUSION: This large study of international, multi-center experience demonstrates excellent survival after lung transplantation using DCD donors. It should be further evaluated whether the mechanism of donor death influences survival after DCD transplant. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.

Dominant discourses tend to represent young people as politically apathetic, disengaged and inert. Yet, in late 2010, tens of thousands of young people across the UK protested against government proposals to change the ways in which higher education is funded. In numerous universities across the country, students occupied buildings, facilitated protests and challenged university leaders to speak out against the proposed changes. At Newcastle University, a group of highly organised students occupied the Fine Art lecture theatre for seventeen days in late 2010 in resistance to these changes. In this paper, we draw upon a detailed analysis of twenty-seven interviews with young people who participated in the Newcastle Occupation, supplemented by participant observation of Occupation meetings. We argue that the students created an intentionally dialogic space in the Occupation in a number of ways, including how they organised it, how they used social media and the internet, the actions they participated in and the ways in which they engaged with the elite. These insights offer an important contribution to debates and young people and politics and exemplify the ways in which the student activists involved in the Newcastle Occupation were sophisticated political agents who strategically and tactfully engaged with politics matters.

In this paper, we take an intersectional approach, and examine how gender, religion, class and place intersect and shape the political participations of young Muslim women in Scotland. In particular, we demonstrate how gendered Islamophobia, class status and the political geographies of Scotland are central factors for shaping political identities and political participations. First, we show that although our participants experience discriminatory processes of gendered Islamophobia, which can result in complex barriers to participation, there is also a political confidence, with many engaging in politics and civic life through a variety of mechanisms. For many, participation is motivated by the understanding that it is a way of countering stereotypes of “Muslim women” and the multiple discriminations they face. Second, we examine how the class backgrounds of the young women influence and play a role in their political participations. We argue that class related factors such as education, social mobility and social capital shape and enable their political participations. Third, we demonstrate how the political geographies of Scotland have worked as a politics of belonging, engendering the participation of many of the young Muslim women in Scottish society.

Purpose Alveolar macrophages are key regulators of the innate immune response and participate in the stem cell niche to organise tissue repair and lung homeostasis . The fate of donor alveolar macrophages is poorly understood as existing studies have relied on sex chromosome labelling or HLA typing methodologies. We sought to confirm the existence of a long-lived pool of donor-derived alveolar macrophages using single cell RNA sequencing in sex mismatched lung transplant patients. Methods BAL cells from 17 individuals, including 11 non-transplant (7 female) and 6 lung transplant recipients (3 male->female, 1 female->male) were isolated and sorted for live cells. Single cells were captured and barcoded using the 10X Genomics Single Cell 3′ Gene Expression platform. Sequencing data was filtered and aligned to human reference genome and count tables analysed in Seurat and Monocle packages. Results Our analysis revealed 2 transcripts specific to female and male cells respectively; XIST (X-inactive specific transcript) and RPS4Y1 (Ribosomal Protein S4 Y-Linked 1) with 70% of cells able to be sex matched (Table1). Of 4 sex mismatched lung transplant patients, only 1 male 8.4 months post-transplant, had alveolar macrophages of donor origin (17.5%). Engrafting monocytes acquired a near identical phenotype to donor macrophages, with trajectory inference of recipient cells revealing arrested expression of genes associated with chemotaxis (CCL2) and tissue remodelling (TIMP1) and upregulation of scavenger receptor (MSR1) and lipid metabolism (FABP4 and SCD) genes (Figure 1). Conclusion Our work questions the existence of long-lived self-renewing populations of alveolar macrophages. Knowledge of the transcriptional programs associated with cell fate transition from peripheral blood derived monocyte to alveolar macrophage will aid in deciphering the pathogenesis of lung diseases involving monocyte/macrophage lineages.

Purpose Severely limited functional status with poor rehabilitation potential is considered an absolute contraindication to lung transplantation. However, defining a threshold of functional status or rehabilitation potential suitable for active listing is complex. Therefore, the study aim was to determine if candidates pre-transplant quadriceps strength along with demographics and respiratory function can predict six-minute walk distance (6MWD) at three months post-transplant. Methods This study used a prospective observational repeated measures design. All lung transplant recipients at a single institution between Dec 2006 and May 2018 were considered for inclusion. Candidates’ demographics (age, sex, lung condition) and transplant hospital admission length of stay were recorded.6MWD, and quadriceps strength corrected for body weight (QS%) were recorded pre- and three months post-transplant. Results 278 lung transplant recipients (142 male; mean age 45.7 ± 14.2 years; FEV133.6 ± 18.6%; 92 cystic fibrosis, 83 chronic obstructive pulmonary disease (COPD), 39 idiopathic pulmonary fibrosis) were studied. Pre-transplant 6MWD was 380.5 ± 138.6m and QS% was 98.8 ± 26.4%. Three months post-transplant 6MWD was 503.3 ± 116.2m. In a multivariate linear regression analysis, increased QS% pre-transplant(β=0.81, p=0.001), younger age(β=-1.59, p=0.011), male recipients (β=29.24, p=0.011), and reduced length of stay post-transplant (β=-2.77, p=0.001) were identified as independent predictors of increased 6MWD. In addition, a diagnosis of COPD (β=-64.47, p=0.001) or idiopathic pulmonary fibrosis (β=-51.96, p=0.017) independently predicted reduced 6MWD at three months post-transplant. Conclusion Pre-transplant quadriceps strength, age, sex, and diagnosis are independent predictors of post-transplant six-minute walk distance. Of these identified measures, onlypre-transplant quadriceps strength is potentially modifiable. Quadriceps strength should be considered when assessing candidacy and should be a key outcome measure when assessing efficacy of interventions designed to improve post-transplant outcomes.

In this paper, we analyse the short term mission experiences of young UK Christians volunteering in Latin America to explore the relationships between international volunteering, faith and subjectivity. We draw on understandings of global citizenship and cosmopolitanism as processes rather than end points to reveal the contingent and multilayered ways subjectivities evolve and are performed through international volunteering. We particularly explore how faith based and secular imaginaries come together to shape a cosmopolitanism that smoothes over inequality and injustice. We highlight the need to acknowledge the multiple ways global subjectivities are expressed by analysing research diaries kept by the young volunteers. These reveal how volunteers’ negotiation of their faith, public imaginaries of development and everyday encounters with inequality, produce instabilities that have significance for thinking about cosmopolitan sensibilities and global citizenship.

Background Because infection has been associated with the development of bronchiolitis obliterans syndrome (BOS), we hypothesized that post-transplant hypogammaglobulinemia would be associated with infection and BOS. Methods Cross-sectional levels of serum immunoglobulins were measured on 2 occasions in our transplant cohort and models developed to explain serum immunoglobulin levels and BOS-free survival. Results A total of 139 patients (median age, 46.6 years) were evaluated at 47 months (range, 15–74 months) after transplant, and 87 were re-evaluated at 72 months (40–107 months). Of this cohort, 44% were immunoglobulin (Ig) G deficient and levels remained stable across the study period, and 27% were IgA deficient and levels fell slightly over time ( p = 0.003). Both immunoglobulin classes were lower in patients with a history of invasive fungal infection, whereas IgA levels were lower in patients with a history of community-acquired respiratory viral infection. Low IgG was independently associated with shorter BOS-free survival (hazard ratio, 0.79; 95% confidence interval, 0.71–0.88; p Conclusion Serum immunoglobulin deficiency is common after lung transplantation and is associated with community-acquired respiratory viral infection, invasive fungal infection, and BOS.

Very soon after the World Trade Center attacks on September 11th 2001, political geography underwent something of a terror turn e a significant refocusing of attention on the war on terror that led to some important work on geopolitics, terrorism and securitisation. Every disciplinary turn has its emphases and omissions, and perhaps inevitably this turn has constructed the events it studies in unintended ways. In particular, there have been many assertions about the impacts of the war on terror on everyday life, yet relatively little attention to empirical evidence. The World Trade Center attacks were rapidly heralded as marking a sea-change for global politics and for local social, political and spatial relations, although recent interventions have emphasised continuities as well as breaks with the past (Gregory & Pred, 2007; Hopkins & Smith, 2008). Further, the flurry of work has been dominated by analyses that centre on ‘big’ politics and the global as the most pressing issue and scale of analysis. As political geographers, we have not always paused to reflect on what is taking place at other scales, as a part of, or despite, the ‘big’ processes. I have written elsewhere (Pain, 2009, 2010) about the dangers of ascribing fear as a taken for granted effect of the war on terror and securitisation; it has been a consistent theme in political geography since 2001. Hopkins’ text is one of the first in a growing group of studies to question some of these assumptions and reorient our attention.

Influenza A H1N1 2009 led to 189 deaths during the Australian pandemic. Community-acquired respiratory viruses not only can cause prolonged allograft dysfunction in lung transplant recipients but have also been linked to bronchiolitis obliterans syndrome (BOS). We report the impact of the 2009 H1N1 pandemic on Australian lung transplant recipients. An observational study of confirmed H1N1 cases was conducted across five Australian lung transplant programs during the pandemic. An electronic database collected patient demographics, clinical presentation, management and outcomes up to a year follow-up. Twenty-four H1N1 cases (mean age 43 ± 14 years, eight females) were identified, incidence of 3%. Illness severity varied from upper respiratory tract symptoms only in 29% to lung allograft dysfunction (≥10% decline FEV1) in 75% to death in 5 (21%) cases (pre-existing BOS grade 3, n = 4). Treatment with oseltamivir occurred in all but one case confirmed after death, reduced immunosuppression, n = 1, augmented corticosteroid therapy, n = 16, and mechanical/noninvasive ventilation, n = 4. There was BOS grade decline within a year in six cases (32%). In conclusion, Australian lung transplant recipients were variably affected by the H1N1 pandemic mirroring the broader community with significant morbidity and mortality. After initial recovery, a considerable proportion of survivors have demonstrated BOS progression.

See Related Article, page 1418 Antibody mediated rejection (AMR) is a recognized cause of hyperacute rejection, along with acute and chronic allograft dysfunction, after lung transplantation. Donorspecific anti-human leukocyte antigen (HLA) antibodies (DSAs) are typically associated with AMR and compromised lung allograft survival. Until recently, no standardized diagnostic criteria existed for pulmonary AMR, and as a result, the AMR Working Group was established by the International Society for Heart and Lung Transplantation with the primary aim of providing a formal consensus definition. Levine et al outlined such a consensus report in the Journal of Heart and Lung Transplantation in April 2016 with a clear overview of pathology of AMR and staging into clinical and sub-clinical phenotypes. Nonetheless, significant questions remain whether DSAs detected by highly sensitive and specific single-antigen bead assays are clinically relevant and predictive of poor graft function in an individual patient. Not all DSAs induce tissue inflammation, with multiple studies confirming upwards of 40% of lung transplant recipients with DSAs but no clinical evidence of AMR. Furthermore, the functional consequences of a detected DSA should not be extrapolated by the mean fluorescence intensity (MFI) because this neither reflects the injurious potential nor the titre of the relevant antibody. The detection and clinical importance of circulating DSAs may be further weakened by the diagnostic limitations in the testing platforms and limited binding affinity of the antibody with the donor antigen target. Some authors have also postulated whether absorption of all sera DSAs into a transplanted organ may further limit detection of antibody within the circulation, impeding a major diagnostic criterion of AMR. The addition of C4d staining of transbronchial biopsy specimens often highlights

The 6-minute walk distance (6MWD) is a widely used clinical indicator of exercise capacity. Although used as part of the assessment process in determining a candidate's suitability for lung transplantation (LT), the literature describing the impact of the 6MWD in predicting survival on LT waiting lists is limited. This study aimed to determine the hazard function associated with the 6MWD, and its utility relative to other prognostic variables.A retrospective chart review was conducted on 163 patients who were listed for single or double LT, and either survived to transplant or died while on the waiting list. A Cox regression for survival analysis, stratified by diagnostic group, was conducted utilizing the 6MWD, demographic variables and measures of cardiopulmonary function.The 6MWD proved to be the only significant covariate in the Cox regression for survival analysis (p0.001), with all other variables eliminated as non-significant. Furthermore, there was a protective effect for each unit increase in the 6MWD [Exp (B) = 0.994, 95% confidence interval 0.990 to 0.997].This research demonstrates that the 6MWD is useful for stratifying patients on the LT waiting list by identifying those patients with a significantly higher risk of mortality.

Parvovirus B19 (PVB) is a non-enveloped, single-stranded DNA virus of the Parvoviridae family pathogenic to humans. Despite numerous case reports of pure red cell aplasia in lung transplant (LT) recipients after PVB infection, the epidemiology remains poorly outlined. Over a 3-year period, 3 of 54 LT patients with unexplained anemia tested positive for circulating PVB by a nested polymerase chain reaction (PCR) assay. All of these patients presented with anemia and leukopenia, with a favorable long-term prognosis.

Objective To assess the safety and early clinical results of a multicenter evaluation of airway bypass with paclitaxel-eluting stents for selected patients with severe emphysema. Methods Airway bypass was performed with a fiberoptic bronchoscope in three steps: identification of a blood vessel–free location with a Doppler probe at the level of segmental bronchi, fenestration of the bronchial wall, and placement of a paclitaxel-eluting stent to expand and maintain the new passage between the airway and adjacent lung tissue. All adverse events were recorded, as well as 1- and 6-month pulmonary function tests and dyspnea index. Results Thirty-five patients received the airway bypass procedure with a median of 8 stents implanted per patient. At 1-month follow-up, statistically significant differences in residual volume, total lung capacity, forced vital capacity, forced expiratory volume, modified Medical Research Council scale, 6-minute walk, and St George's Respiratory Questionnaire were observed. At the 6-month follow-up, statistically significant improvements in residual volume and dyspnea were demonstrated. One death occurred after bleeding during the procedure. Retrospective analysis revealed that the degree of pretreatment hyperinflation may be an important indicator of which patients achieve the best short- and long-term results. Conclusions The airway bypass procedure reduces hyperinflation and improves pulmonary function and dyspnea in selected patients with severe emphysema. Duration of benefit appears to correlate with the degree of pretreatment hyperinflation. These preliminary clinical results support further evaluation of the procedure.

Background Ischemia–reperfusion injury (IRI) is a prominent cause of primary graft failure after lung transplantation and is associated with an altered surfactant profile. Experimental animal studies have found that replacement with exogenous surfactant administered via fiber-optic bronchoscopy (FOB) enhanced recovery from IRI with improved pulmonary compliance and gas exchange after lung transplantation. We report our clinical experience with FOB instillation of surfactant in severe IRI after human lung transplantation. Methods This study is a retrospective review of 106 consecutive lung or heart–lung transplants performed at a single institution. Severe IRI was defined as diffuse roentgenographic alveolar infiltrates, worsening hypoxemia and decreased lung compliance within 72 hours of lung transplantation. One vial of surfactant (20 mg/ml phospholipid) was instilled into each segmental bronchus upon diagnosis of IRI. Results Six patients (5 bilateral sequential and 1 re-do heart–lung transplant), mean age 46 years, were diagnosed with IRI and surfactant was administered at a mean of 37 hours (range 2.3 to 98) post-transplant. Mean graft ischemia time was 376 minutes (range 187 to 625) and cardiopulmonary bypass time 174 minutes (range 0 to 210). Mean Pao 2 [mm Hg]/Fio 2 ratio before and 48 hours after surfactant instillation was 70 and 223, respectively. Significant resolution of radiologic infiltrates was evident in all cases within 24 hours. Successful extubation occurred at a mean of 13.5 days and survival is presently 100% at 19 months (range 3 to 54). Conclusions Bronchoscopic instillation of surfactant improves oxygenation and prognosis after severe IRI in lung transplant recipients. It represents a cost-effective, relatively non-invasive therapeutic alternative to extracorporeal membrane oxygenation.

s S43 Recipients of larger volumes of MSC (2 and 4 million cells/kg) have shown no improvement in FEV1 but have only 2 months follow at the time of this report (See Figure 2). Conclusion: Preliminary results from this study suggest a beneficial effect on lung function derived from low volume infusion of allogeneic bone-marrow derived MSC. This effect may not occur on recipients of larger volumes of stem cells but longer follow up is needed.

Many lung transplant programs now use organs from donors after circulatory death (DCD). However, brain dead donors far outnumber DCD donors, particularly in the United States. At 12 years after the first report of a DCD transplant by Love et al, the numbers of DCD transplants in the United States remained dismal at a utilization rate of 1.9%. To obtain more information related to the infrequent use of DCD lungs, the International Society for Heart and Lung Transplantation (ISHLT) DCD working group performed a survey in 2014. The group sent separate questionnaires to active and non-active DCD centers. Of the 62 centers that responded to the survey, 50% of them had active DCD programs. Of the non-active DCD centers, 82% expressed interest in initiating a DCD program. Centers with and centers without DCD programs had similar perceptions of outcomes of DCD lung transplantation. About 80% of all respondents believed that lung transplant outcomes for recipients of DCD and brain dead donors have similar results. Regarding the primary reason for not using DCD donors, 85% of respondents stated that the main barriers consisted of complex logistics and absence of protocols related to DCD. Some centers also expressed concerns about starting a DCD program without having ex vivo lung perfusion technology (EVLP) in place. The medical literature contains detailed protocols that lead to successful DCD recovery with and without EVLP. DCD recovery requires a trained team of surgeons for the lung retrieval; however, some transplant teams overstate the complexity of the procedure. Once mechanical ventilation is restored after asystole and death declaration, flushing and preservation of the lungs occurs in a similar fashion as for DBD donation. The exact role of EVLP in category 3 DCD has not been established. Excellent results have been obtained without the routine use of EVLP. In contrast, EVLP may help to exclude lungs with injuries that have not been recognized after withdrawal of life support therapies (i.e., aspiration) and may help to expand more safely the utilization criteria for DCDs, including the acceptance of longer agonal times. Logistical issues, such as absence of protocols and insufficient numbers of trained personnel, create the primary obstacles to initiating and maintaining a successful DCD program. Because 30% to 40% of potential DCD donors do not go into cardiac arrest in a suitable time frame (60–90 minutes) for donor lung recovery, economic constraints also affect the willingness of transplant programs to use DCD. Transplant centers would be hesitant to send a team to a donor site if significant travel and operating room costs would be incurred if the lungs will not be evaluated because of absence of donor cardiac arrest in a suitable time. Better predictive tools for probability of cardiac arrest, collaboration with retrieval teams at donor sites, and creative ideas of lung preservation after cardiac arrest so that transplant teams may not need to be on standby before death is declared may overcome these limitations. Key priorities for successful use of DCD in lung transplantation in the near future should consist of knowledge transfer, education, and overcoming logistical barriers.

"Culture-negative" wound infection and mediastinitis secondary to Mycoplasma hominis have been reported after cardiothoracic surgery but no case cluster has ever been described. We report 4 cases of infection in 3 cardiac and 1 bilateral sequential lung transplant recipient over 3 weeks of hospitalization. Successful treatment was achieved with early aggressive surgical intervention and combination antibiotics of clindamycin, doxycycline and/or ciprofloxacin. This cluster raises the question of nosocomial transmission of infection and supports a recommendation for single-room isolation and universal precautions for infected individuals.

Background: Post-transplant lymphoproliferative disease (PTLD) is a serious, often fatal complication after solid organ transplantation. Primary Epstein-Barr virus (EBV) infection is the major risk factor for PTLD after lung transplantation, with 30% to 50% of EBV-naive patients who seroconvert and are diagnosed with PTLD. Method: In this study, we analyzed the incidence of PTLD in lung and heart–lung transplant recipients before 1996 (historic group) and then compared the impact of long-term anti-viral prophylaxis on the development of PTLD in EBV-seronegative recipients from January 1996 to December 2000 (post-1996 group). Routine induction therapy was not given after 1995. Patients not surviving 30 days, 25 of 341 (7.3%), were excluded. Results: Historic group: PTLD developed in 7 of 167 (4.2%) patients, at a mean of 394 ± 278 (95–885) days. The mortality was 87.5% at a mean follow-up of 186 ± 207 (17–520) days after diagnosis. Post-1996 group: Eighteen of 149 (12.3%) patients were EBV seronegative at the time of transplantation, and of these 15 (83%) began receiving continuous anti-viral prophylaxis: acyclovir or valacyclovir or ganciclovir from January 1996. None of the EBV-seronegative recipients receiving continuous anti-viral prophylaxis were diagnosed with PTLD; however, 1 of 3 (33%) of the EBV-seronegative recipients who did not receive anti-viral prophylaxis were diagnosed with PTLD. In the EBV-seronegative recipients, no deaths had been caused by PTLD at a mean follow-up of 806 ± 534 (39–1,084) days. In the post-1996 group, PTLD developed in 1 of 131 (0.76%) EBV-seropositive recipients. Conclusion: Continuous, specific anti-viral prophylaxis in high-risk EBV-seronegative recipients significantly reduces the incidence of PTLD after lung transplantation in the absence of induction therapy.

Study objectives: To assess the utility of nasopharyngeal tube insertion in the management of hypoxemia during flexible bronchoscopy (FB) in lung transplant recipients, and to determine the incidence and risk factors of upper-airway obstruction (UAO) leading to significant hypoxemia during FB. Setting: Heart-lung transplant unit of a university hospital. Patients and methods: Ninety-six lung transplant recipients (47 men and 49 women; mean SD age, 41.4 13.1 years) underwent 714 FB procedures from January 1997 to May 2000. Intervention: A fall in oxygen saturation (< 90%) in patients receiving 6 L/min of oxygen via nasal prongs was treated with insertion of a nasopharyngeal tube, continued oxygen supplementation, and withdrawal of the bronchoscope to the trachea. If oxygen desaturation persisted at < 90% despite additional oxygen administration via a 7F catheter placed either just above the larynx or in the proximal trachea, the bronchoscope was withdrawn, reversal of sedation was administered, and bag and mask ventilation was instituted until satisfactory spontaneous ventilation was achieved. Results: Forty-six patients (47.9%) were treated with nasopharyngeal tube insertion on 102 occasions at a mean duration of 168 178 days after lung transplantation. In 90 of 102 procedures (88.2%), significant hypoxemia due to UAO was successfully treated with nasopharyngeal tube insertion. The mean oxygen saturation after nasopharyngeal tube insertion was 97 3%. Male gender, increase in body mass index after lung transplantation, and presence of obstructive sleep apnea were significant factors associated with the need for nasopharyngeal tube insertion during FB in lung transplant recipients. Conclusions: Significant oxygen desaturation during FB in lung transplant recipients is mainly due to UAO. Insertion of a nasopharyngeal tube is a novel and a highly effective approach to the management of acute hypoxemia during FB. (CHEST 2002; 121:1350–1354)

Ajay J. Iyengar , David S. Winlaw , Leeanne E. Grigg , David S. Celermajer , Yves d’Udekem 1 Department of Cardiac Surgery, Royal Children’s Hospital, Melbourne, Australia Heart Centre for Children, The Children’s Hospital at Westmead, Sydney, Australia Department of Cardiology, The Royal Melbourne Hospital, Melbourne, Australia Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia Corresponding author.