Sarcoidosis lung transplantation waitlist mortality, a national registry database study.

Background: The Lung Allocation Score (LAS) prioritises lung transplantation candidates, balancing waitlist mortality and post-transplant survival. The score groups sarcoidosis candidates based on mean pulmonary artery pressure: those with ≤30 mmHg (sarcoidosis A) are grouped with COPD and those with >30 mmHg (sarcoidosis D) with idiopathic pulmonary fibrosis (IPF). We hypothesise that sarcoidosis candidates have a higher waitlist mortality than other candidates within their LAS grouping. Methods: This is a retrospective cohort study of consecutive lung transplantation candidates from the Scientific Registry of Transplant Recipients database from May 2005 to May 2019. We included candidates aged ≥18 years diagnosed with sarcoidosis, COPD or IPF. Univariate, multivariate and survival estimate analyses were performed. Results: We identified 385 sarcoidosis A, 642 sarcoidosis D, 7081 COPD and 10 639 IPF lung transplantation candidates. 17.3% of sarcoidosis D, 14.8% of IPF, 14.3% of sarcoidosis A and 9.8% of COPD candidates died awaiting transplant. Sarcoidosis A was an independent risk factor for waitlist mortality. Sarcoidosis A had a lower waitlist survival probability compared to COPD. Sarcoidosis D had the highest waitlist mortality. IPF candidates had lower waitlist survival probability than sarcoidosis D in the first 60 days after listing. Conclusion: Based on our results, the grouping of candidates with sarcoidosis in allocation systems should be revised to mitigate waitlist mortality disparity.

Predictors of lung transplant waitlist mortality for sarcoidosis.

RATIONALE: Unlike in other chronic lung diseases, criteria for lung transplant referral in sarcoidosis is not well-established. Waitlist mortality may offer clues in identifying clinical factors that warrant early referral. We aim to identify predictors for transplant waitlist mortality to improve referral criteria for patients with sarcoidosis. METHODS: We conducted a retrospective analysis of 1034 sarcoidosis patients listed for lung transplantation from May 2005 to May 2019 in the Scientific Registry of Transplant Recipients (SRTR) database. All patients were listed after the establishment of the Lung Allocation Score (LAS). We compared patients who died on the transplant waitlist to those who survived to transplantation. Potential predictors of waitlist mortality were assessed utilizing univariate and multivariate analysis performed via logistic regression modeling. RESULTS: Of 1034 candidates listed after LAS implementation, 704 were transplanted and 110 died on the waitlist. Significant predictors of waitlist mortality on multivariate analysis include female gender (OR 2.445; 95% CI 1.513-3.951; p = 0.0003) and severe pulmonary hypertension (OR 1.619; 95% CI 1.067-2.457; p = 0.0236). Taller minimum donor height (OR 0.606; 95% CI 0.379-0.969; p = 0.0365) and blood type B (OR 0.524; 95% CI 0.281-0.975 p = 0.0415) were associated with decreased likelihood of death on the waitlist. CONCLUSION: Among patients with sarcoidosis on the lung transplant waitlist, taller minimum donor height and blood type B were found to be protective factors against death on the waitlist. Female gender and severe pulmonary hypertension have a higher likelihood of death and earlier referral for transplantation in patients with these characteristics should be considered.

Bronchoscopic lung volume reduction: status quo.

Emphysema is associated with irreversible loss of lung compliance leading to gas trapping and hyperinflation. Surgical lung volume reduction has proven to improve lung function, exercise capacity, cardiac health and survival in patients with advanced emphysema; however, this procedure is associated with significant morbidity and mortality. Bronchoscopic lung volume reduction (BLVR) has emerged as an alternative approach for these patients. In this article, we review the different techniques used for the purpose of this procedure, its advantages and disadvantages. In addition, we discuss in length valve therapy and the studies that led to its recent FDA approval. Finally, we provide thought-provoking challenges that may be topics for further future investigation to enhance the efficacy and benefit of this technique.

Sleep Duration and Efficiency Associated With Better Functional Exercise Capacity in Black Smokers at Risk for COPD.

BACKGROUND: Black smokers have earlier development of lung disease as well as poorer sleep health than whites. RESEARCH QUESTION: In a sample of black smokers, to what extent does sleep health modify the association between smoking level and functional exercise capacity? DESIGN AND METHODS: Cross-sectional data from 209 black smokers (≥ 1 cigarette in last month), aged 40 to 65 years with no evidence of sleep-disordered breathing (apnea-hypopnea index < 15) or severe COPD (FEV1 > 50%), were used for the current study. Self-reported smoking rate, objectively measured sleep efficiency (SE), total sleep time (TST), and the 6-min walk test (6MWT) for functional exercise capacity were the key assessments. RESULTS: The mean age was 54.8 years (SD, 5.96), and mean cigarettes smoked per day (cpd) was 8.71 (SD, 6.78). Mean SE was 69.9% (SD, 12.3%), and mean TST was 307.99 min (SD 92.2). In adjusted linear regression models of the 6MWT (meters), TST (slope estimate, -0.14; P = .14) and SE (slope estimate, -1.0; P = .19) were negatively associated with 6MWT. The smoking rate × SE interaction was highly significant (slope estimate, 0.18; P = .007) such that in individuals who smoked ≥ 10 cpd, every additional percentage of SE garnered an additional distance of 0.83 to 6.62 m. Similarly, the smoking rate × TST interaction was significant (slope estimate, 0.019; P = .03) such that in smokers who smoked ≥ 10 cpd, every additional minute of TST garnered an additional distance of 0.04 to 0.60 m. INTERPRETATION: Higher SE and, to a lesser extent, longer TST, in black adults who smoke ≥ 10 cpd is associated with better 6MWT performance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03534076; URL: www.clinicaltrials.gov.

Mortality for sarcoidosis patients on the transplant wait list in the Lung Allocation Score era: Experience from a high volume center.

RATIONALE: Sarcoidosis progresses to end stage fibrotic lung disease in 10% of patients and may necessitate lung transplantation. Organ allocation is currently determined by the Lung Allocation Score (LAS), but its performance in a sarcoidosis population has not been evaluated. OBJECTIVES: To determine sarcoidosis-specific wait list mortality and identify predictive factors of death on the transplantation wait list. METHODS: This was a single-center retrospective study of all sarcoidosis patients listed for lung transplant from March 2012 to February 2019. We compared patients who were transplanted to those who died awaiting organs. We collected baseline listing characteristics, physiologic testing, and outcomes data. Statistical analysis was performed by 2-tailed Student's t-test, Mann-Whitney U test, and Chi-Square analysis (where appropriate). Receiver-operating characteristic curves were constructed for variables reaching statistical significance. RESULTS: Twenty eight sarcoidosis patients were included in analysis. Mortality among wait listed patients was 18%, which exceeded the mortality of COPD and IPF. LAS scores did not differ at initial listing (41 vs. 46, p = 0.35) or at transplant/death (41 vs. 41, p = 0.91); wait list times also did not statistically differ (307 days vs. 177 days, p = 0.19). We identified bilirubin (AUC = 0.92), DLCO (AUC = 0.84), FEV1/FVC at transplant/death (AUC = 0.85), and composite physiologic index (AUC = 0.86) as predictors of death on the transplant list. Pulmonary hypertension was not associated with death. CONCLUSION: Unexpected sudden death was common in our cohort and was associated with markers of advanced fibrotic disease, not pulmonary hypertension.

Coagulopathy and functional hyposplenism during an episode of thrombotic thrombocytopenic purpura in a HgbS/ß (+)-thalassemia patient.

We report a case of TTP in a sickle cell/ß+-thalassemia heterozygote with nonspecific complaints and a evidence of hemolysis, initially attributed to sickle crisis. Included in this case is a discussion of the development of functional hyposplenism, a rarely reported complication, limitation of ADAMTS-13 in diagnosis, and the use of platelet transfusion.

Drosophila lilliputian is required for proneural gene expression in retinal development.

BACKGROUND: Proper neurogenesis in the developing Drosophila retina requires the regulated expression of the basic helix-loop-helix (bHLH) proneural transcription factors Atonal (Ato) and Daughterless (Da). Factors that control the timing and spatial expression of these bHLH proneural genes in the retina are required for the proper formation and function of the adult eye and nervous system. RESULTS: Here we report that lilliputian (lilli), the Drosophila homolog of the FMR2/AF4 family of proteins, regulates the transcription of ato and da in the developing fly retina. We find that lilli controls ato expression at multiple enhancer elements. We also find that lilli contributes to ato auto-regulation in the morphogenetic furrow by first regulating the expression of da prior to ato. We show that FMR2 regulates the ato and da homologs MATH5 and TCF12 in human cells, suggesting a conservation of this regulation from flies to humans. CONCLUSIONS: We conclude that lilliputian is part of the genetic program that regulates the expression of proneural genes in the developing retina.

Identification of novel regulators of atonal expression in the developing Drosophila retina.

Atonal is a Drosophila proneural protein required for the proper formation of the R8 photoreceptor cell, the founding photoreceptor cell in the developing retina. Proper expression and refinement of the Atonal protein is essential for the proper formation of the Drosophila adult eye. In vertebrates, expression of transcription factors orthologous to Drosophila Atonal (MATH5/Atoh7, XATH5, and ATH5) and their progressive restriction are also involved in specifying the retinal ganglion cell, the founding neural cell type in the mammalian retina. Thus, identifying factors that are involved in regulating the expression of Atonal during development are important to fully understand how retinal neurogenesis is accomplished. We have performed a chemical mutagenesis screen for autosomal dominant enhancers of a loss-of-function atonal eye phenotype. We report here the identification of five genes required for proper Atonal expression, three of which are novel regulators of Atonal expression in the Drosophila retina. We characterize the role of the daughterless, kismet, and roughened eye genes on atonal transcriptional regulation in the developing retina and show that each gene regulates atonal transcription differently within the context of retinal development. Our results provide additional insights into the regulation of Atonal expression in the developing Drosophila retina.