From 6-wk Lungs to 6 y: Increasing the Donor Pool for Pediatric Lung Transplantation.

BACKGROUND: Lung transplantation in the pediatric population is a challenge. With the donor pool being so small and lungs from young donors rare and precious, every organ available needs to be utilized to its best potential. CASE: Here, we describe the case of a 6-wk-old donor of double lungs to a 5-mo-old baby girl diagnosed with alveolar capillary dysplasia with misalignment of the pulmonary veins. The recipient is doing very well, 6 y after the transplant, now following normal growth. DISCUSSION: The challenges facing pediatric cardiothoracic transplantation in terms of organ supply and demand are enormous. CONCLUSIONS: In this article, we discuss some of the issues around the shortage of organs and alternatives to increase the organ donor pool.

Disparities in lung transplantation in children.

Lung transplantation is a recognized therapy for end-stage respiratory failure in children and young people. It is only available in selected countries and is limited by access to suitable organs. Data on disparities in access and outcomes for children undergoing lung transplantation are limited. It is clear from data from studies in adults, and from studies in other solid organ transplants in children, that systemic inequities exist in this field. While data relating specifically to pediatric lung transplantation are relatively sparse, professionals should be aware of the risk that healthcare systems may result in disparities in access and outcomes following lung transplantation in children.

Feasibility and Efficacy of Life Review Delivered by Virtually-Trained Family Caregivers.

BACKGROUND: Due to the high prevalence of depressive symptoms and Alzheimer's disease and related dementias in older Americans (≥65 years), we developed a six-week depression intervention, Caregiver-Provided Life Review (C-PLR) for care recipients (CRs) with early-stage dementia and mild depression. OBJECTIVE: The objective of the study was to examine the feasibility and efficacy of C-PLR delivered by virtually-trained caregivers (CGs) on CRs who live with dementia and depression in community and long-term care settings (N = 25 CG-CR dyads). METHODS: We used fidelity scores as a measure of CG's feasibility to provide C-PLR. We collected the pre- and post-measures on CRs' depression (primary outcome), life satisfaction, CGs' burden, positive aspects of caregiving, and CG-CR relationship quality (secondary outcomes) and compared them using paired t-tests. We evaluated if the effect differed by race/ethnicity, residential setting, or living alone. RESULTS: The average fidelity check-in score was 14.8±0.78 indicating high feasibility. CGs were 52 years old (mean), 88% female, 64% working, 72% college-educated, and 72% in good-excellent health. CRs were 81 years old (mean), 84% female, and 56% in poor-fair health. CRs' depression significantly improved (p < 0.001), and this effect was found in CRs who were Asian (p = 0.017), White (p = 0.040), community-dwelling (p < 0.001), lived alone (p = 0.045), or with others (p = 0.002). CONCLUSION: This study demonstrated that the C-PLR can be successfully taught to CGs virtually and is effective in reducing CR's depressive symptoms. C-PLR could be implemented more broadly to improve symptoms among CRs in community and residential settings, as well as among a diverse population of CRs.

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

INTRODUCTION: A new UK Lung Allocation Scheme (UKLAS) was introduced in 2017, replacing the previous geographic allocation system. Patients are prioritised according to predefined clinical criteria into a three-tier system: the super-urgent lung allocation scheme (SULAS), the urgent lung allocation scheme (ULAS) and the non-urgent lung allocation scheme (NULAS). This study assessed the early impact of this scheme on waiting-list and post-transplant outcomes. METHODS: A cohort study of adult lung transplant registrations between March 2015 and November 2016 (era-1) and between May 2017 and January 2019 (era-2). Outcomes from registration were compared between eras and stratified by urgency tier and diagnostic group. RESULTS: During era-1, 461 patients were registered. In era-2, 471 patients were registered (19 (4.0%) SULAS, 82 (17.4%) ULAS and 370 (78.6%) NULAS). SULAS patients were younger (median age 35 vs 50 and 55 for urgent and non-urgent, respectively, p=0.0015) and predominantly suffered from cystic fibrosis (53%) or pulmonary fibrosis (37%). Between eras 1 and 2, the odds of transplantation within 6 months of registration were increased (OR=1.41, 95% CI 1.07 to 1.85, p=0.0142) despite only a 5% increase in transplant activity. Median time-to-transplantation during era-1 was 427 days compared with waiting times in era-2 of 8 days for SULAS, 15 days for ULAS and 585 days for NULAS patients. Waiting-list mortality (15% era-1 vs 13% era-2; p=0.5441) and post-transplant survival at 1 year (81.3% era-1 vs 83.3% era-2; p=0.6065) were similar between eras. CONCLUSION: The UKLAS scheme prioritises the critically ill and improves transplantation odds. The true impact on waiting-list mortality and post-transplant survival requires further follow-up.

Case formulation-A vehicle for change? Exploring the impact of cognitive behavioural therapy formulation in first episode psychosis: A reflexive thematic analysis.

OBJECTIVES: Formulation is considered a fundamental process of cognitive behavioural therapy for psychosis (CBTp). However, an exploration into the personal impact of different levels of case formulation (CF) from a service user (SU) perspective is lacking, particularly for those experiencing a first episode of psychosis. DESIGN: This Big Q qualitative design used semi-structured interviews. METHODS: Reflexive thematic analysis (TA) was used to analyse 10 participant interviews. NVivo 12 computer-assisted qualitative data analysis software aided data organisation and analysis. RESULTS: One overarching theme 'CF - A vehicle for change?' was developed as a pattern of shared meaning across the data set. Three main themes related to the overarching theme: (1) Vicious cycles: 'I never really thought about it being me maintaining the problems' (including one subtheme - Self-empowerment: 'Only you can make the changes for yourself'); (2) Early life experiences: 'My experiences have shaped the person that I am, therefore, it's not my fault' (including one subtheme - Disempowerment: '[My] core beliefs have been damaged'); and (3) Keep it simple: 'Don't push it too far over the top in case it becomes like spaghetti'. CONCLUSIONS: Maintenance formulations may be experienced as self-blaming, but also self-empowering, which may help to facilitate change. Longitudinal formulations may be experienced as non-blaming, but also disempowering, which may inhibit change. Simple CF diagrams may also facilitate change, whereas overly complex CFs may inhibit change. How CBTp therapists might look to improve the impact of different levels of CF for service users (SUs) in first episode psychosis (FEP) are described.

Lung transplantation in an 18-month-old with donor specific antibodies - The use of intraoperative, targeted plasma exchange.

BACKGROUND: Sensitised patients undergoing Human Leukocyte Antigen-incompatible transplantation are at increased risk of hyperacute rejection and may be predisposed to antibody-mediated rejection, chronic lung allograft dysfunction and higher mortality. CASE: We present a case of primary lung transplantation in the setting of late identification of donor specific antibodies treated with intraoperative target plasma exchange. The patient was treated with fresh human plasma to a final volume of 1.5 times the patient's systemic circulation. From a pre-transplant mean fluorescence intensity of 5002, donor-specific antibodies were undetectable following plasma exchange on single antigen bead assay. CONCLUSIONS: This method represents a potential desensitisation technique for use in the intraoperative period.

Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease.

BACKGROUND: Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification. METHODS: Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid. RESULTS: No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. CONCLUSIONS: Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.

Can short PROMs support valid factor-based sub-scores? Example of COMQ-12 in chronic otitis media.

PURPOSE: Interpretable factor solutions for questionnaire instruments are typically taken as justification for use of factor-based sub-scores. They can indeed articulate content and construct validities of a total and components but do not guarantee criterion validity for clinical application. Our previous documentation of basic psychometric characteristics for a 12-item patient-reported outcome measure in adult chronic otitis media (COMQ-12) justified next appraising criterion validity of sub-scores. METHODS: On 246 cases at 1st clinic visit, we compared various classes of factor solution, concentrating on the best-fitting 3-factor ones as widely supported. Clinical data offered two independent measures as external criteria: binaural hearing (audiometric thresholds measured via audiometry) for evaluating 'Hearing' sub-score, and oto-microscopic findings for the 'Ear discharge symptoms' sub-score. As criterion for the total, and for semi-generic 'Activities/healthcare' sub-score, the generic Short Form-36 item set offered a widely used multi-item criterion measure. RESULTS: Factor model fit and parsimony again favoured a 3-factor solution for COMQ-12; however insufficient item support and the dominant 1st principal component of variation made sub-scoring problematic. The best solution was bi-factor, from which only the weighted total score met the declared convergent validity standard of r = 0.50. Two of the more specific sub-scores ('Ear discharge symptoms' and 'Hearing') correlated poorly with clinical findings and weighted binaural hearing thresholds. CONCLUSION: The COMQ-12 total is acceptably content-valid for general clinical purposes, but the small item set, reflecting excessive pressure for brevity in clinical application, does not well support three criterion-valid factor-based scores. This distinction should be made explicit, and profile sub-scoring discouraged until good convergent and furthermore divergent criterion validities are shown.

Gains in Quality of Life in Chronic Otitis Media Patients After Surgery, Adjusted for Placebo Bias.

OBJECTIVE: Using a short-form specific questionnaire, we sought to quantify specific and generic benefits of surgery for chronic otitis media (COM) while adjusting for expectancy (placebo) bias. STUDY DESIGN: A prospective observational pretreatment/posttreatment study. SETTING: A national tertiary referral center. PATIENTS: Consecutive adult COM patients were enrolled for 1 year. Of 246 patients, 205 were recommended for surgery, and 167 were operated on the (more) affected ear. INTERVENTIONS: All patients filled out two questionnaires, one specific (Chronic Otitis Media Questionaire-12) and one generic (Short Form-36) at baseline, and then again 6 and 12 months after surgery. MAIN OUTCOME MEASURES: Factor-based scores of questionnaires, standardized response means (SRMs) for treatment effects, with multiple linear regression for implementing bias adjustment. RESULTS: All but one (generic Short Form-36 "mental" scale) of the seven considered measures gave very highly significant ( p < 0.001) improvements. Unadjusted SRMs were large (1.0-2.0 standard deviation units) for audiometry, symptoms of ear discharge, reported hearing, and aggregate specific quality of life, but only moderate for the less specific activity/healthcare. The proposed bias adjustment reduced SRM magnitudes for most measures by about a third, for activity/healthcare and ear discharge by only a tenth to a fifth, and for audiometry not at all. CONCLUSION: Most scores of the specific questionnaire displayed definite placebo-like biases; this demands caution in interpreting improvement after COM surgery. With bias adjustments, credible and worthwhile magnitudes of improvements remained for Chronic Otitis Media Questionnaire-12 total and subscores (0.5-1.09 standard deviation SRM), but not for generic quality of life.

What are the essential ingredients of a CBT case conceptualization for voices and delusions in schizophrenia spectrum disorders? A study of expert consensus.

Evidence supports the use of cognitive behavioural therapy (CBT) for the treatment of patients with schizophrenia spectrum disorders. A case conceptualization (CC) (or case formulation) is seen as the keystone of CBT in terms of making sense of a patient's difficulties, to guide and inform such treatment. Despite the importance placed on CC there is no known consensus amongst experts as to the essential ingredients involved in this fundamental process. This study used the Delphi method to establish expert consensus for the essential components of a CC when working to treat auditory hallucinations (voices), and persecutory delusions. An international panel of 78 CBT for psychosis (CBTp) experts from 12 different countries participated in the main stage of this study. This 3-stage process involved producing and rating statements that addressed key areas of CC in terms of: presenting issues, predisposing, precipitating, perpetuating and protective factors. One presenting issue and 6 perpetuating factors were endorsed as essential by >80% of the expert panel. The exact same items were endorsed for both voices, and persecutory delusions. The findings are unique in that a large panel of international experts reached consensus that case conceptualizations (CCs) should be parsimonious and focused on the perpetuating (maintaining) factors to facilitate change. Overall, the proposed recommendations should lead to core guidance for the process of developing CCs, and improvements in training for clinicians that conceptualize voices, and persecutory delusions in CBT for schizophrenia spectrum disorders.

Inhaled hypertonic saline after pediatric lung transplant-Caution required?

Management of pulmonary infection following lung transplant is multifaceted and includes respiratory physiotherapy. Inhaled hypertonic saline (HTS) has been introduced as an adjunct to physiotherapy in pediatric transplant patients. There are no published studies investigating the use of HTS in this population. This study aimed to evaluate the effect of inhaled HTS, in the acute post-operative period, in pediatric lung transplant patients. A retrospective case-note review was completed at a single UK pediatric transplant center. An intervention group who received HTS was compared to a historical control group. Participants were frequency matched for age, gender, and diagnosis (14 per group); median age in years was 13.7(IQR 12.7-15.3) in the controls and 14.8(IQR 12.4-16.1) in the intervention group. Primary outcome was the requirement of invasive and non-invasive ventilation. Secondary outcomes included oxygen use and length of stay. Median days of invasive ventilation were shorter in the control group (1, 95% CI 1-1) compared to the intervention group (2, 95% CI 1-2.5) (P < .05). Days of non-invasive ventilation and oxygen were higher in the HTS group, but this was not statistically significant. The controls displayed shorter median length of stay (23 days, 95% CI 20-24) compared to the intervention group (31 days, 95% CI 24.5-39) (P < .05). The results of this small study provide uncertainty regarding the safety of inhaled hypertonic saline after lung transplant. There was a trend of poorer acute outcomes in patients who received HTS. However, the findings should be interpreted with caution and further investigation using larger samples is required.

Cell-Free DNA in Pediatric Solid Organ Transplantation Using a New Detection Method of Separating Donor-Derived from Recipient Cell-Free DNA.

BACKGROUND: The use of cell-free DNA (cfDNA) as a noninvasive biomarker to detect allograft damage is expanding rapidly. However, quantifying the low fraction of donor-derived cfDNA (ddcfDNA) is challenging and requires a highly sensitive technique. ddcfDNA detection through unique donor single nucleotide polymorphisms (SNPs) is a recent new approach, however there are limited data in pediatric solid organ transplant (SOT) recipients. METHODS: We developed an assay using a combination of 61 SNPs to quantify the ddcfDNA accurately using a custom R script to model for both the patient and donor genotypes requiring only a single sample from the allograft recipient. Performance of the assay was validated using genomic DNA (gDNA), cfDNA and donor samples where available. RESULTS: The R "genotype-free" method gave results comparable to when using the known donor genotype. applicable to both related and unrelated pairs and can reliably measure ddcfDNA (limit of blank, below 0.12%; limit of detection, above 0.25%; limit of quantification 0.5% resulting in 84% accuracy). 159 pediatric SOT recipients (kidney, heart, and lung) were tested without the need for donor genotyping. Serial sampling was obtained from 82 patients. CONCLUSION: We have developed and validated a new assay to measure the fraction of ddcfDNA in the plasma of pediatric SOT recipients. Our method can be applicable in any donor-recipient pair without the need for donor genotyping and can provide results in 48 h at a low cost. Additional prospective studies are required to demonstrate its clinical validity in a large cohort of pediatric SOT recipients.

Pediatric lung transplantation: Results of volume reduction in smaller children.

Pediatric LTX is challenged by the scarcity of suitable donor organs. To alleviate the problem of size matching, volume reduction of the donor is a possible option. Previous reports address mostly older teenagers, and data about younger patients are lacking. The purpose of this study was to investigate whether trimming had influence on the morbidity and mortality in slightly younger recipients, operated in a single center. Between 2015 and 2018, 20 patients were transplanted at the GOSH London. The mean age was 11.5 (±4.6) years. Nine patients underwent volume reduction prior to transplantation (T group). The other patients received classical bilateral LTX (NT group). Ischemia times were longer in the T group, but this difference was not statistically significant. We observed no 30-day mortality. Hospital survival in the T group was 78% vs 90% in the NT group. After almost 3 years, mortality in the T group was 22% vs 28% in the NT group. None of these differences was statistically significant. The mean duration of MV, intensive care stay, and hospital stay were 11.5, 19.9, and 44.8 days, respectively. Results were equal in terms of morbidity, defined as respiratory and neurological complications or the need for ECMO. Results show that volume reduction prior to LTX is a feasible option, even in smaller children. While awaiting long-term results, accepting larger donor organs could be a strategy to further reduce waiting list time and subsequently lower the mortality on the waiting list.

Outcome according to subspecies following lung transplantation in cystic fibrosis pediatric patients infected with Mycobacterium abscessus.

BACKGROUND: Mycobacterium abscessus infection has been associated with variable outcomes following lung transplantation. M abscessus comprises three subspecies (M abscessus subsp abscessus, M abscessus subsp massiliense, and M abscessus subsp bolletii). We investigated whether lung transplantation outcome in cystic fibrosis (CF) patients in a single center was related to the M abscessus subspecies and genetic cluster. METHODS: CF patients with chronic M abscessus infection transplanted at Great Ormond Street Hospital between 2004 and 2017 were retrospectively examined. All M abscessus isolates were identified to subspecies level by polymerase chain reaction and sequencing. Genetic cluster was determined by variable number tandem repeat profiling and whole-genome sequencing (WGS), and sequence type inferred from WGS. RESULTS: Thirteen patients with chronic M abscessus infection underwent heart/lung or lung transplantation. Subspecies identification showed n = 1 with M abscessus bolletii, n = 5 with M abscessus massiliense, and n = 7 with M abscessus abscessus infection. Eight (62%) patients (one with M abscessus massiliense and seven with M abscessus abscessus) died post-lung transplant. The patient with M abscessus bolletii and three patients with M abscessus massiliense did well post-transplant. One patient with M abscessus massiliense is receiving ongoing treatment. CONCLUSIONS: Dramatically worse outcomes are observed in patients infected with M abscessus subspecies abscessus, the majority of whom were infected with ST-1 and ST-26 strains. Patients infected with other M abcsessus strains can have acceptable outcomes.

The LINC00961 transcript and its encoded micropeptide, small regulatory polypeptide of amino acid response, regulate endothelial cell function.

AIMS: Long non-coding RNAs (lncRNAs) play functional roles in physiology and disease, yet understanding of their contribution to endothelial cell (EC) function is incomplete. We identified lncRNAs regulated during EC differentiation and investigated the role of LINC00961 and its encoded micropeptide, small regulatory polypeptide of amino acid response (SPAAR), in EC function. METHODS AND RESULTS: Deep sequencing of human embryonic stem cell differentiation to ECs was combined with Encyclopedia of DNA Elements (ENCODE) RNA-seq data from vascular cells, identifying 278 endothelial enriched genes, including 6 lncRNAs. Expression of LINC00961, first annotated as an lncRNA but reassigned as a protein-coding gene for the SPAAR micropeptide, was increased during the differentiation and was EC enriched. LINC00961 transcript depletion significantly reduced EC adhesion, tube formation, migration, proliferation, and barrier integrity in primary ECs. Overexpression of the SPAAR open reading frame increased tubule formation; however, overexpression of the full-length transcript did not, despite production of SPAAR. Furthermore, overexpression of an ATG mutant of the full-length transcript reduced network formation, suggesting a bona fide non-coding RNA function of the transcript with opposing effects to SPAAR. As the LINC00961 locus is conserved in mouse, we generated an LINC00961 locus knockout (KO) mouse that underwent hind limb ischaemia (HLI) to investigate the angiogenic role of this locus in vivo. In agreement with in vitro data, KO animals had a reduced capillary density in the ischaemic adductor muscle after 7 days. Finally, to characterize LINC00961 and SPAAR independent functions in ECs, we performed pull-downs of both molecules and identified protein-binding partners. LINC00961 RNA binds the G-actin sequestering protein thymosin beta-4x (Tß4) and Tß4 depletion phenocopied the overexpression of the ATG mutant. SPAAR binding partners included the actin-binding protein, SYNE1. CONCLUSION: The LINC00961 locus regulates EC function in vitro and in vivo. The gene produces two molecules with opposing effects on angiogenesis: SPAAR and LINC00961.

Language in schizophrenia and aphasia: the relationship with non-verbal cognition and thought disorder.

Objective: To determine the relationship between language abnormalities and broader cognitive impairment and thought disorder by examining language and cognition in schizophrenia and aphasia (a primary language disorder).Methods: Cognitive and linguistic profiles were measured with a battery of standardised tests, and compared in a clinical population of n = 50 (n = 30 with schizophrenia and n = 20 with aphasia) and n = 61 non-clinical comparisons (n = 45 healthy controls and n = 16 non-affected first-degree relatives of patients with schizophrenia).Results: Both clinical groups showed linguistic deficits. Verbal impairment was more severe in participants with aphasia, whereas non-verbal performance was more affected in participants with schizophrenia. In schizophrenia, but not in aphasia, verbal and non-verbal performance were associated. Formal thought disorder was associated with impairment in executive function and in grammatical, but not naming, tasks.Conclusion: While patients with schizophrenia and aphasia showed language impairments, the nature and cognitive basis of these impairments may be different; language performance disassociates from broader cognitive functioning in aphasia but may be an intrinsic expression of a broader cognitive impairment in schizophrenia. Thought disorder may represent a core malfunction of grammatical processing. Results suggests that communicative ability may be a valid target in cognitive remediation strategies in schizophrenia.

Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus.

A 15-year-old patient with cystic fibrosis with a disseminated Mycobacterium abscessus infection was treated with a three-phage cocktail following bilateral lung transplantation. Effective lytic phage derivatives that efficiently kill the infectious M. abscessus strain were developed by genome engineering and forward genetics. Intravenous phage treatment was well tolerated and associated with objective clinical improvement, including sternal wound closure, improved liver function, and substantial resolution of infected skin nodules.

Role of TPBG (Trophoblast Glycoprotein) Antigen in Human Pericyte Migratory and Angiogenic Activity.

Objective- To determine the role of the oncofetal protein TPBG (trophoblast glycoprotein) in normal vascular function and reparative vascularization. Approach and Results- Immunohistochemistry of human veins was used to show TPBG expression in vascular smooth muscle cells and adventitial pericyte-like cells (APCs). ELISA, Western blot, immunocytochemistry, and proximity ligation assays evidenced a hypoxia-dependent upregulation of TPBG in APCs not found in vascular smooth muscle cells or endothelial cells. This involves the transcriptional modulator CITED2 (Atypical chemokine receptor 3 CBP/p300-interacting transactivator with glutamic acid (E)/aspartic acid (D)-rich tail) and downstream activation of CXCL12 (chemokine [C-X-C motif] ligand-12) signaling through the CXCR7 (C-X-C chemokine receptor type 7) receptor and ERK1/2 (extracellular signal-regulated kinases 1/2). TPBG silencing by siRNA transfection downregulated CXCL12, CXCR7, and pERK (phospho Thr202/Tyr204 ERK1/2) and reduced the APC migratory and proangiogenic capacities. TPBG forced expression induced opposite effects, which were associated with the formation of CXCR7/CXCR4 (C-X-C chemokine receptor type 4) heterodimers and could be contrasted by CXCL12 and CXCR7 neutralization. In vivo Matrigel plug assays using APCs with or without TPBG silencing evidenced TPBG is essential for angiogenesis. Finally, in immunosuppressed mice with limb ischemia, intramuscular injection of TPBG-overexpressing APCs surpassed naïve APCs in enhancing perfusion recovery and reducing the rate of toe necrosis. Conclusions- TPBG orchestrates the migratory and angiogenic activities of pericytes through the activation of the CXCL12/CXCR7/pERK axis. This novel mechanism could be a relevant target for therapeutic improvement of reparative angiogenesis.

Successful lung donation at the age of 6 weeks: Challenges and lessons learned.

A clinical case of successful procurement and transplantation of bilateral lungs from 6-week-old infant with sepsis secondary to bacterial meningitis is reported. Forty-one-day-old male infant (height 60 cm, weight 4 kg) died of cerebral edema secondary to Escherichia coli meningitis and bacteremia. Preretrieval assessment included the following: arterial gases; pO2 50.4 kPa (378 mm Hg), pCO2 4.9 kPa (37 mm Hg), on FiO2 100%, PEEP 5 cm H2 O. Fiberoptic bronchoscopy showed no secretions nor mucosal inflammation; CXR revealed clear lung fields and pleural spaces. Inspection revealed dense adhesions in pericardial cavity and purulent left hemithorax effusion (urgent Gram-stain came back as negative) but there was no consolidation in the lung. Good compliance of the lungs on inflation/deflation test was observed. The lungs were retrieved using the technique described. The recipient was a 4-month-old infant with alveolar capillary dysplasia and malaligned pulmonary veins. Implantation of the lungs was performed via bilateral thoracosternotomy on cardiopulmonary bypass, cooling to 30°C. Elective support with nitric oxide was used postoperatively. Two years after the transplantation, the recipient doing well with normal lung function. Lung procurement from a 6-week donor with infectious complications and prolonged ventilation is a challenging undertaking but can be successful and should be attempted whenever possible given the paucity of organs available for pediatric recipients.