The latest medical research on Transplant Pulmonology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about transplant pulmonology gathered by our medical AI research bot.

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Pre-transplant factors associated with mortality after lung transplantation in cystic fibrosis: A systematic review and meta-analysis.

J Cyst Fibros

Mortality risk stratification is essential in lung transplantation (LTx) to allow listing, prioritization and mitigating strategies. In cystic fibrosis (CF) patients, predictors of post-LTx mortality are not established.

For this systematic review and meta-analysis, seven databases were searched until January 3, 2018 to identify predictors of post-LTx mortality in CF. We excluded studies of multi-organ transplantation, re-transplantation and graft survival. For multiple studies assessing the same population during overlapping time-periods, the largest one was analyzed. Risk of bias was assessed with the Newcastle-Ottawa scale (NOS). Pooled hazard ratios were calculated using random-effects models.

Fifty-four studies were included in the systematic review and 11 studies in the meta-analyses (low-to-moderate bias risk, NOS score ≥ 5). Among 10 factors assessed in the meta-analysis, B. cepacia complex (BCC) (N = 1451, unadjusted HR = 2.35, 95%CI:1.80-3.06; I2 = 20.4% and adjusted HR = 2.49, 95%CI:1.74-3.57; I2 = 46.2%) and ascending chronological year of LTx (N = 4207, unadjusted HR = 0.98, 95%CI:0.97-0.98, I2 = 4.8%) were predictors of post-LTx mortality. Male gender (N = 2903, adjusted HR = 1.12, 95%CI:1.0-1.26, I2 = 0%) and age in adults (N = 3677, unadjusted HR = 0.99, 95%CI:0.97-1.00; I2 = 64.1% and N = 2605, adjusted HR = 0.98, 95%CI:0.97-0.99; I2 = 34.3%) had borderline significant associations with post-LTx mortality. P. aeruginosa colonization, forced expiratory volume in one second (FEV1), pulmonary hypertension, body mass index (BMI), pancreatic insufficiency and CF-related diabetes (CFRD) were not predictors of mortality.

BCC was associated with a higher post-LTx mortality whereas FEV1, pulmonary hypertension, BMI, CFRD and female gender were not associated with post-LTx mortality. These findings indicate that CF-specific risk estimates of post-LTx mortality should be considered.

The lung and gut microbiome: what has to be taken into consideration for cystic fibrosis?

J Cyst Fibros

The 15th European Cystic Fibrosis Society (ECFS) Basic Science pre-conference Symposium focused on the topic of the microbiome, asking the question...

Urinary metabolomics reveals unique metabolic signatures in infants with cystic fibrosis.

J Cyst Fibros

United States ClinicalTrials.Gov registry NCT01424696 (clinicaltrials.gov).

Urine metabolomics was performed for 85 infants with predefined clinical phenotypes at approximately one year of age enrolled in BONUS via Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Samples were stratified by disease status (non-CF controls (n = 22); CF (n = 63, All-CF)) and CF clinical phenotype: respiratory hospitalization (CF Resp, n = 22), low length (CF LL, n = 23), and low weight (CF LW, n = 15).

Global urine metabolomics profiles in CF were heterogeneous, however there were distinct metabolic differences between the CF and non-CF groups. Top pathways altered in CF included tRNA charging and methionine degradation. ADCYAP1 and huntingtin were identified as predicted unique regulators of altered metabolic pathways in CF compared to non-CF. Infants with CF displayed alterations in metabolites associated with bile acid homeostasis, pentose sugars, and vitamins.

Predicted metabolic pathways and regulators were identified in CF infants compared to non-CF, but metabolic profiles were unable to discriminate between CF phenotypes. Targeted metabolomics provides an opportunity for further understanding of early CF disease.

Cystic fibrosis is associated with an increased risk of Barrett's esophagus.

J Cyst Fibros

Cystic fibrosis (CF) patients have increased risks of gastrointestinal cancers, including esophageal adenocarcinoma. Gastroesophageal reflux disease (GERD) is highly prevalent in CF and manifests at early ages. CF patients may be at increased risk for long-term sequelae of chronic GERD, including Barrett's esophagus (BE). We aimed to assess whether patients with CF have an increased risk of BE or related neoplasia.

A matched cohort study was performed of adults with and without CF who had undergone upper endoscopy. Non-CF patients were matched in a 4:1 ratio by age, sex, year of exam, and endoscopist. Odds ratios were calculated for the association between CF and BE or related neoplasia, and multivariable logistic regression modeling was performed to adjust for matching variables and additional potential confounders.

122 CF patients underwent endoscopy, and 488 matched controls were identified. Seven (5.7%) CF patients had BE or related neoplasia, including one GE junction adenocarcinoma. Mean age of affected CF patients was 36.0, and 85.7% had a prior solid organ transplant. The odds of BE was significantly increased in CF patients (OR 2.91, 95% CI 1.08-7.81). The risk remained significantly increased in a multivariable model including matching variables (OR 3.32, 95% CI 1.19-9.22) and in a parsimonious model (OR 2.99, 95% CI 1.06-8.42).

Adults with CF have a 3-fold increased risk of BE or related neoplasia and appears to develop at younger ages. Consideration should be given to screening for BE in select CF patients, especially those who have undergone solid organ transplantation.

Dental and periodontal manifestations in patients with cystic fibrosis - A systematic review.

J Cyst Fibros

The oral cavity is an important reservoir of microorganisms and can be a potential source of infection of the respiratory tract in CF patients. The literature on the oral health does not explicitly determine dental problems in these patients. The aim of the study was to systematically review the studies relating to oral status in CF patients.

A systematic review of papers published from 1997 to 2018 regarding oral status in CF children and adults, carried out in accordance with the Cochrane Collaboration guidelines.

The search resulted in 143 studies. Thirteen publications were included in the systematic review.

The role of illness uncertainty in the relationship between disease knowledge and patient-reported outcomes among adolescents and adults with congenital heart disease.

Heart and Lung

Greater general disease knowledge predicts better patient-reported outcomes (PROs) among congenital heart disease (CHD) survivors, but higher illness uncertainty is associated with elevated emotional distress and poorer well-being among patients with chronic disease.

This study explored the relationship of illness uncertainty and disease knowledge with emotional distress and health-related quality of life (HRQoL) among patients with CHD.

Individuals with CHD (N = 169, ages 15-39) completed self-report measures of disease knowledge (general and risk-related), illness uncertainty, depressive and anxiety symptoms, and HRQoL. Pearson correlations and regressions analyses were utilized.

Greater risk-related knowledge was associated with greater anxiety (b = .41, p = .03, 95% CI = [.04, .77]) and poorer emotional HRQoL (b = -.53, p = .03, 95% CI = [-1.02, -.05]) when illness uncertainty was higher.

When individuals with CHD feel uncertain about their disease course and outcomes, knowledge about future cardiovascular risks may result in higher levels of distress.

Markers of cardiogenic shock predict persistent acute kidney injury after out of hospital cardiac arrest.

Heart and Lung

Ischemia and reperfusion injury (IRI) in cardiac arrest patients after return to spontaneous circulation causes dysfunctions in multiple organs. Kidney injury is generally transient but in some patients persists and contributes both to mortality and increased resource utilisation. Ongoing shock may compound renal injury from IRI, resulting in persistent dysfunction. We tested whether cardiac dysfunction was associated with the development of persistent acute kidney injury (PAKI) in the first 72 h after cardiac arrest.

We performed an observational retrospective study from January 2013 to April 2017. We included consecutive patients treated after out-of-hospital cardiac arrest at a single academic medical center with renal function measured and immediately and for 48 h post arrest. We also recorded each patient's pre arrest baseline creatinine, demographic and clinical characteristics. Our primary outcome of interest was PAKI, defined as acute kidney injury (AKI) on at least 2 measurements 24 h apart. We compared demographics and outcomes between patients with PAKI and those without, and used logistic regression to identify independent predictors of PAKI.

Of 98 consecutive patients, we excluded 24 for missing data. AKI was present in 75% of subjects on arrival. PAKI developed in 35% of patients. PAKI patients had a longer hospital length of stay (median 21 vs 11 days) and lower hospital survival (47% vs 71%). Serum lactate levels, dosage of adrenaline during resuscitation and days of dobutamine infusion strongly predicted PAKI.

Among patient who survive cardiac arrest, acute AKI is common and PAKI occurs in more than one third. PAKI is associated both with survival and with length of stay at the hospital. High doses of adrenaline, high serial serum lactate levels, and dose of dobutamine predict PAKI. Evaluation of the trajectory of renal function over the first few days after resuscitation can provide prognostic information about patient recovery.

Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis.

J Cyst Fibros

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. In this study we assessed the effect of antisense oligonucleotide eluforsen on CFTR biological activity measured by Nasal Potential Difference (NPD) in patients with the most common mutation, F508del-CFTR.

This multi-centre, exploratory, open-label study recruited adults with CF homozygous or compound heterozygous for the F508del-CFTR mutation. Subjects received intranasal eluforsen three times weekly for 4 weeks. The primary endpoint was the within-subject change from baseline in total chloride transport (Cl-free+iso), as assessed by NPD. Secondary endpoints included within-subject change from baseline in sodium transport.

In the homozygous cohort (n = 7; per-protocol population), mean change (90% confidence interval) in Cl-free+iso was -3.0 mV (-6.6; 0.6) at day 15, -4.1 mV (-7.8; -0.4, p = .04) at day 26 (end of treatment) and - 3.7 mV (-8.0; 0.6) at day 47. This was supported by improved sodium transport as assessed by an increase in average basal potential difference at day 26 of +9.4 mV (1.1; 17.7, p = .04). The compound heterozygous cohort (n = 7) did not show improved chloride or sodium transport NPD values. Eluforsen was well tolerated with a favourable safety profile.

In F508del-CFTR homozygous subjects, repeated intranasal administration of eluforsen improved CFTR activity as measured by NPD, an encouraging indicator of biological activity.

Family presence during resuscitation (FPDR): A qualitative descriptive study exploring the experiences of emergency personnel post resuscitation.

Heart and Lung

Family presence during resuscitation (FPDR), remains inconsistently implemented by emergency personnel. The benefits for family members is well documented, providing opportunities for family to say goodbye, facilitates closure and enables family to provide emotional support to the patient. The aim of this study was to explore the experiences and attitudes of emergency personnel towards FPDR immediately post resuscitation events.

A descriptive qualitative design was used to explore the experiences of emergency personnel with FPDR. Data was collected from single rural and metropolitan emergency departments in the state of Victoria, Australia. The participants consisted of nurses and doctors who took active roles during resuscitation events. Following transcription of the audiotaped interviews Creswell's (2003) six step analysis process was employed.

A total of 29 interviews of key personnel, following 6 paediatric and 18 adult resuscitation events. Interviews were conducted over a period of two weeks in each venue. The data was organised into six themes following analysis including: care coordinators inconsistently called, gate keepers to implementation, effective communication strategies helping to deliver bad news, life experience generates confidence, allocation of family support person, and family members roles dependent on age of patient.

FPDR is common practice in paediatric events however remains inconsistently implemented during adult resuscitations. A designated family support person is essential to successful implementation of FPDR and should be incorporated in to the allocation of the resuscitation team roles during both adult and paediatric resuscitation events. Education and training is important for clinicians to learn essential communication skills, building practice confidence, which is required to successfully implement FPDR.

Design and rationale of the B-lines lung ultrasound guided emergency department management of acute heart failure (BLUSHED-AHF) pilot trial.

Heart and Lung

Medical treatment for acute heart failure (AHF) has not changed substantially over the last four decades. Emergency department (ED)-based evidence for treatment is limited. Outcomes remain poor, with a 25% mortality or re-admission rate within 30 days post discharge. Targeting pulmonary congestion, which can be objectively assessed using lung ultrasound (LUS), may be associated with improved outcomes.

BLUSHED-AHF is a multicenter, randomized, pilot trial designed to test whether a strategy of care that utilizes a LUS-driven treatment protocol outperforms usual care for reducing pulmonary congestion in the ED. We will randomize 130 ED patients with AHF across five sites to, a) a structured treatment strategy guided by LUS vs. b) a structured treatment strategy guided by usual care. LUS-guided care will continue until there are ≤15 B-lines on LUS or 6h post enrollment. The primary outcome is the proportion of patients with B-lines ≤ 15 at the conclusion of 6 h of management. Patients will continue to undergo serial LUS exams during hospitalization, to better understand the time course of pulmonary congestion. Follow up will occur through 90 days, exploring days-alive-and-out-of-hospital between the two arms. The study is registered on ClinicalTrials.gov (NCT03136198).

If successful, this pilot study will inform future, larger trial design on LUS driven therapy aimed at guiding treatment and improving outcomes in patients with AHF.

Pseudomonas aeruginosa colonization causes PD-L1 overexpression on monocytes, impairing the adaptive immune response in patients with cystic fibrosis.

J Cyst Fibros

Cystic fibrosis (CF) is an endotoxin tolerance (ET)-related disease. Given that increased PD-L1 has been reported in ET, its expression and physiological effects on cystic fibrosis monocytes should be studied.

We analyzed the phenotype and ex vivo response of immune system cells in 32 patients with CF, 19 of them colonized by Pseudomonas aeruginosa. An in vitro model was developed of Pseudomonas aeruginosa colonization using purified lipopolysaccharides (LPS) from one of the most prevalent strains in patients with CF (a CF-adapted Pseudomonas aeruginosa ST395 clone). Changes in the immune response, including cytokine production and T-lymphocyte proliferation, as well as expression of PD-L1, were evaluated.

PD-L1 was overexpressed in the monocytes of patients with CF compared with healthy volunteers, and levels of this immune checkpoint were associated with Pseudomonas aeruginosa colonization. In addition, patients with Pseudomonas aeruginosa colonization showed a patent ET status, including poor inflammatory response, reduced HLA-DR expression and T-lymphocyte proliferation impairment. PD-L1/PD-1 blocking assays reverted the impaired adaptive response. Ultimately, monocytes from healthy volunteers cultured in the presence of the clinically relevant strain of Pseudomonas aeruginosa or serum collected from patients with CF colonized by Pseudomonas aeruginosa reproduced the previous observed features.

Pseudomonas aeruginosa colonization in patients with CF was associated with PD-L1 overexpression and impaired T cell response, and LPS from this pathogen induced the observed phenotype. Our findings open new avenues for the use of anti-PD-1/PD-L1 immunotherapy in patients with CF who are colonized by Pseudomonas aeruginosa.

Regional disparity in outcomes among patients hospitalized for Takotsubo cardiomyopathy in the United States✰.

Heart and Lung

Takotsubo cardiomyopathy (TTCM), an entity first described in Japan over two decades ago following myocardial stunning cases without evidence of coronary stenosis, has emerged as a unique entity with global recognition. We sought to investigate the extent and magnitude of regional variations in its outcomes.

We used the National Inpatient Sample (NIS) of the Agency for Healthcare Research and Quality (2010-2014). Risk-adjusted rates of outcomes across the US geographical regions were calculated by fitting a Poisson regression model with a robust error variance under generalized estimating equations. Discrete numeric variables with over-dispersed count distributions -length of stay and continuous variables with a right skewed spread- cost of hospitalization were modeled using a generalized linear regression with a negative binomial function and gamma function respectively.

We found significant regional variations in-patient mortality. While there was significantly higher risk of in-hospital death in the West (5.28 [4.34-6.44]) vs 4.40 [3.57-5.43] vs 4.10 [3.38-498] vs 4.78 [3.96-5.77]), there was a different pattern of variation in the length of days with longer hospital stay in the Northeast. Likewise, the risk-adjusted rate of non-routine home discharges was highest for Northeast. The West had the highest cost of hospitalization (West: $40,217 vs. South: $28,465) CONCLUSION: Significant geographic variation exists in the cost of hospitalization and in-hospital mortality of TTCM across the US. Understanding this variation requires a detailed understanding of the processes of care and identification of effective strategies to eliminate these disparities.