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Rationale It remains unclear how gastroesophageal reflux disease (GERD) affects allograft microbial community composition in lung transplant recipients and its impact on lung allograft inflammation and function. Objectives Our objective was to compare the allograft microbiota in lung transplant recipients with or without clinically diagnosed GERD in the first year after transplant and assess associations between GERD, allograft microbiota, inflammation, and acute and chronic lung allograft dysfunction (ALAD and CLAD). Methods A total of 268 BAL samples were collected from 75 lung transplant recipients at a single transplant center every 3 months after transplant for 1 year. Ten transplant recipients from a separate transplant center provided samples before and after antireflux Nissen fundoplication surgery. Microbial community composition and density were measured using 16S ribosomal RNA gene sequencing and quantitative polymerase chain reaction, respectively, and inflammatory markers and bile acids were quantified. Measurements and Main Results We observed a range of allograft community composition with three discernible types (labeled community state types [CSTs] 1–3). Transplant recipients with GERD were more likely to have CST1, characterized by high bacterial density and relative abundance of the oropharyngeal colonizing genera Prevotella and Veillonella . GERD was associated with more frequent transitions to CST1. CST1 was associated with lower inflammatory cytokine concentrations than pathogen-dominated CST3 across the range of microbial densities observed. Cox proportional hazard models revealed associations between CST3 and the development of ALAD/CLAD. Nissen fundoplication decreased bacterial load and proinflammatory cytokines. Conclusions GERD was associated with a high bacterial density, Prevotella- and Veillonella- dominated CST1. CST3, but not CST1 or GERD, was associated with inflammation and early development of ALAD and CLAD. Nissen fundoplication was associated with a reduction in microbial density in BAL fluid samples, especially the CST1-specific genus, Prevotella .

We identified 42 patients with spirometrically-significant AR, 56 patients with stable AR, and 81 patients with stable no-AR with available BAL samples (one sample per patient). BAL at time of spirometrically-significant AR, compared to other groups, had elevated levels of TCA (ANOVA<0.05), as well as markers of inflammation (IL6, CXCL8, S100A8, IL1b, and S100A12) (ANOVA<0.05 for all). In multivariable models, levels of GCA and TCA were associated with allograft survival independent of AR group (P<0.05 for both). These are preliminary results that are now being reviewed by co-authors from all sites. Additional analyses are ongoing. This is an ancillary study of the CTOT-20 multi-center trial: approval of the abstract by the CTOT publication committee is pending.

Rationale: Gastroesophageal reflux disease (GERD) may affect lung allograft inflammation and function through its effects on allograft microbial community composition in lung transplant recipients. Objectives: Our objective was to compare the allograft microbiota in lung transplant recipients with or without clinically diagnosed GERD in the first post-transplant year, and assess associations between GERD, allograft microbiota, inflammation and acute and chronic lung allograft dysfunction (ALAD/CLAD). Methods: 268 bronchoalveolar lavage samples were collected from 75 lung transplant recipients at a single transplant centre every 3 months post-transplant for 1 year. Ten transplant recipients from a separate transplant centre provided samples pre/post-anti-reflux Nissen fundoplication surgery. Microbial community composition and density were measured using 16S rRNA gene sequencing and qPCR, respectively and inflammatory markers and bile acids were quantified. Measurements and Main Results: We observed three community composition profiles (labelled community state types, CSTs 1-3). Transplant recipients with GERD were more likely to have CST1, characterized by high bacterial density and relative abundance of the oropharyngeal colonizing genera Prevotella and Veillonella. GERD was associated with more frequent transition to CST1. CST1 was associated with lower per-bacteria inflammatory cytokine levels than the pathogen-dominated CST3. Time-dependant models revealed associations between CST3 and development of ALAD/CLAD. Nissen fundoplication decreased bacterial load and pro-inflammatory cytokines. Conclusion: GERD was associated with a high bacterial density, Prevotella/Veillonella dominated CST1. CST3, but not CST1 or GERD, was associated with inflammation and early development of ALAD/CLAD. Nissen fundoplication was associated with decreases in microbial density in BALF samples, especially the CST1-specific genus, Prevotella.

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Background: Thyrotropin (also known as thyroid stimulating hormone (TSH)) receptors antibodies (TRAb) activate thyroid follicular cells in the autoimmune condition known as Graves' hyperthyroidism, which causes thyrotoxicosis and swelling of the thyroid gland. Objective: Using a thorough retrospective cohort design, this research assessed the effectiveness of antithyroid drugs (ATDs) and risk variables linked to the recurrence of Graves' hyperthyroidism. Methods: With enough follow-up data, we evaluated 2100 individuals who had just received a Graves' hyperthyroidism diagnosis. Evaluation of the treatment results of the subjects and risk factors for recurrence-free survival, particularly alterations in thyrotropin receptors antibodies. Results: The participants' average age was 44.8 years, and 64% of them were females. After using ATD for a median of 22.9 months (interquartile range (IQR) 16.9-34.4), 1450 participants were given the option to discontinue the medication. Initial remission ratio was 56.6%. 95.24% of participants completed the second round of ATD therapy after the initial recurrence and the remission ratio was 56.6%. 7.14% of participants required surgery, and 10.9% received radioactive iodine treatment, throughout the course of a median follow-up duration of 67 months. About 29.7% of patients were still receiving ATD medication for chronic lower-dose maintained or recurring illness. Male gender, being younger (<45 years old), and fluctuating or smoldering of TRAb levels were all distinct risk indicators for the first recurrence following ATD therapy. Conclusions: ATD therapy is a viable choice for both chronic condition and the first therapy of Graves' hyperthyroidism. The individual risk indicators of recurring must be determined to identify the effective therapeutic duration for ATD therapy.