Protective Role of IL-6 in Vascular Remodeling in Schistosoma Pulmonary Hypertension

Schistosomiasis is one of the most common causes of pulmonary arterial hypertension worldwide, but the pathogenic mechanism by which the host inflammatory response contributes to vascular remodeling is unknown. We sought to identify signaling pathways that play protective or pathogenic roles in experimental Schistosoma-induced pulmonary vascular disease via whole-lung transcriptome analysis. Wild-type mice were experimentally exposed to Schistosoma mansoni ova by intraperitoneal sensitization followed by tail-vein augmentation, and the phenotype was assessed by right ventricular catheterization and tissue histology, as well as RNA and protein analysis. Whole-lung transcriptome analysis by microarray and RNA sequencing was performed, and RNA sequencing was analyzed according to two bioinformatics methods. Functional testing of the candidate IL-6 pathway was determined using IL-6 knockout mice and the signal transducers and activators of transcription protein-3 (STAT3) inhibitor S3I-201. Wild-type mice exposed to S. mansoni demonstrated increased right ventricular systolic pressure and thickness of the pulmonary vascular media. Whole-lung transcriptome analysis determined that the IL-6-STAT3-nuclear factor of activated T cells c2(NFATc2) pathway was up-regulated, as confirmed by PCR and the immunostaining of lung tissue from S. mansoni-exposed mice and patients who died of the disease. Mice lacking IL-6 or treated with S3I-201 developed pulmonary hypertension, associated with significant intima remodeling after exposure to S. mansoni. Whole-lung transcriptome analysis identified the up-regulation of the IL-6-STAT3-NFATc2 pathway, and IL-6 signaling was found to be protective against Schistosoma-induced intimal remodeling

Additional file 2: Figure S1. of Unexpected effects of different genetic backgrounds on identification of genomic rearrangements via whole-genome next generation sequencing

Numbers of Candidate SV Calls Before Filtering Process. The numbers of candidate SV calls detected in 10 samples of different genetic backgrounds before any filtering process. The numbers of total SVs include ITX (intra-chromosomal translocations), DELs (deletions), INV (inversions), INS (insertions), and CTXs (inter-chromosomal translocations) in 10 sequenced samples, including 6 tumor samples (119J, 125J, 196J, 202J, 46J, and 90J) and 4 control samples (control 1, control 2, kidney and wt B6) plus 129S1 whose sequences were downloaded from Sanger’s Institute (see details in Methods). (PDF 361 kb

Real-World Implementation of Sickle Cell Transition Programs As Part of a State Quality Improvement Network

The Florida Department of Health's Division of Children's Medical Services administers, with facilitation service from the National Institute for Children's Health Quality, a Statewide Network of Access and Quality program composed of five pediatric hematology-oncology organizations throughout Florida. Recognizing the importance of an adequate transition process to minimize morbidity and even mortality among youth with sickle cell disease (SCD), we have worked together for three years in several projects related to transition including educating medical providers and our own practices about SCD, transition, and GotTransition™ Six Core Elements ®. In June 2022, we began a new project with the aim statement that by December 2023, 80% or higher of the sickle cell patients ages 14-21 years attending clinic at the five hematology centers would have a readiness assessment and a transition plan updated at least once during the previous 12 months as assessed on monthly chart audits. At onset, 486 patients met criteria to be on a transition program due to age and cognitive ability. Two programs had previously participated in The Sickle Cell Trevor Thompson Transition Project (ST3P Up) (NCT 03593395), a Patient-Centered Outcomes Research Institute (PCORI) sponsored sickle cell transition study and learned to implement the GotTransition Six Core Elements. Three programs did not have transition programs implemented. The change ideas were either collective or implemented in a particular program depending on the program decision. The collective change ideas consisted of educating the clinical staff about GotTransition and quality improvement strategies, identifying eligible patients through patient roster, and implementing either monthly audits of ten random charts or reviewing charts of all patients who came the previous month for missed opportunities. The program-specific change ideas consisted of prospective review of patients who were scheduled to come to clinic within the week, staff huddles to discuss patients on transition, conversion of paper-based ASH or TIP-RFT sickle cell readiness assessment into electronic medical record (EMR) version, the use of smart phrases to document the readiness assessment and plan, and sharing ownership of the process with different members of the staff for sustainability. Data and learning from improvement strategies were reviewed twice a month with all group members in virtual one-hour meetings. Two quality improvement consultants encouraged and coached sites. Figures show the run charts of the aggregate data. Per the Health Care Data Guide [Provost and Murray vbk://9781119690122] we used the median of the first three data points as a surrogate baseline in the absence of not having any prior data. We froze and extended the baseline median, looked at data collected after the changes were made and adjusted the median once improvement signals emerged. At the aggregate level, the mean percentage with a readiness assessment increased from 50% in June 2022 to 80% in May 2023 and the median performance throughout the 12 months increased from 50% to 81%. The mean percentage with a transition plan increased from 36% in June 2022 to 80% in May 2023 with an increase in the median performance across the 12 months from 36% to 78%. The activities which were identified as most successful were planning ahead of time to assess patients, having electronic document versions of the readiness assessments and documenting plans with smart phrases on the EMRs. Our network was successful in working together, sharing knowledge, and achieving goals. We plan to assess patient reported outcomes such as patient satisfaction with transition and completion of transition process as future projects

Additional file 1: Table S1 of Unexpected effects of different genetic backgrounds on identification of genomic rearrangements via whole-genome next generation sequencing

The numbers of CTXs in each sample after filtering process and chromosome coordinates of all CTXs. 10 sequenced samples include 6 tumor samples (119J, 125J, 196J, 202J, 46J, and 90J) and 4 control samples (mouse control 1, mouse control 2, kidney and wt B6) plus 129S1 whose sequences were downloaded from Sanger’s Institute (see details in Methods). (XLSX 541 kb