Background Atrial fibrillation (AF) is associated with diffuse left atrial (LA) fibrosis and a reduction in endocardial voltage. These changes are indicators of AF severity and appear to be predictors of treatment outcome. In this study we report the utility of delayed enhancement MRI (DE-MRI) in detecting abnormal atrial tissue prior to radiofrequency ablation and in predicting procedural outcome. Methods and Results Eighty-one patients presenting for pulmonary vein antrum isolation (PVAI) for treatment of AF underwent 3D DE-MRI of the LA prior to the ablation. Six healthy volunteers were also scanned. DE-MRI images were manually segmented to isolate the LA and custom software was implemented to quantify the spatial extent of delayed enhancement, which was then compared to the regions of low voltage from electroanatomical maps from the PVAI procedure. Patients were assessed for AF recurrence at least six months following PVAI with average follow-up of 9.6 ± 3.7 months (range = 6 to 19 months). Based on the extent of pre-ablation enhancement, 43 patients were classified as having minimal enhancement (average enhancement = 8.0% ± 4.2%), 30 as moderate (enhancement = 21.3% ± 5.8%), and 8 as extensive (enhancement = 50.1% ± 15.4%). The rate of AF recurrence was 6 patients (14.0%) with minimal enhancement, 13 (43.3%) with moderate and 6 (75%) patients with extensive enhancement (p <0.001). Conclusion DE-MRI provides a non-invasive means of assessing LA myocardial tissue in patients suffering from AF and might provide insight into the progress of the disease. Pre-ablation DE-MRI holds promise to predict responders to AF ablation and may provide a metric of overall disease progression.

We define noninvasive MRI methods that allow for the detection and quantification of LA wall scarring after RF ablation in patients with AF. Moreover, there seems to be a correlation between the extent of LA wall injury and short-term procedural outcome.

This review should provide a framework for making the proper diagnosis, implementing appropriate treatment, and advising the family about anticipated outcome.

Diarrheal HUS patients presenting with oligoanuria, dehydration, WBC >20 x 10(9)/L, and hematocrit >23% are at substantial risk for fatal hemolytic uremic syndrome. Such individuals should be referred to pediatric tertiary care centers.

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Prior long-term retrospective studies have described renal sequelae in 25-50 % of post diarrheal hemolytic uremic syndrome (D+HUS ) survivors, but the ability to predict the likelihood of chronic renal related sequelae at the time of hospital discharge is limited. We surveyed 357 children in our HUS registry who had survived an acute episode of D+HUS and were without end stage renal disease (ESRD) at the time of hospital discharge. Of the 357 patients surveyed, 159 had at least one year (mean 8.75 years) of follow-up. Of these, 90 individuals were identified as having had at least one day of oliguria, with 69 individuals having had at least one day of anuria. Incidence of renal related sequelae (proteinuria, low glomerular filtration rate [GFR], and hypertension) were determined among experimental groups based on the duration of oliguria and anuria. One or more sequelae (e.g. proteinuria, low GFR, hypertension) were seen in 25 (36.2%) of those who had no recorded oliguria and 34 (37.8%) of those with no recorded anuria. The prevalence of chronic sequelae increased markedly in those with more than 5 days of anuria or 10 days of oliguria; with anuria being a better predictor of most related sequelae than oliguria. A particularly high incidence of hypertension was seen in patients with > 10 days of anuria (55.6%) in comparison to those with no anuria (OR = 12.8; 95% CI = 2.9 to 57.5). Patients with > 10 days of anuria were also at substantially increased risk for low GFR and proteinuria (OR = 35.2; 95% CI = 5.1 to 240.5). These findings may help to identify children who need periodic and extended follow-up after discharge from the hospital.

For most cancers, metastasis is the point at which clinical treatment shifts from curative intent to extending survival. Biomaterial implants acting as a synthetic premetastatic niche recruit metastatic cancer cells and provide a survival advantage, and their use as a diagnostic platform requires assessing their relevance to disease progression. Here, we showed that scaffold-captured tumor cells (SCAF) were 30 times more metastatic to the lung than primary tumor (PT) cells, similar to cells derived from lung micrometastases (LUNG). SCAF cells were more aggressive in vitro, demonstrated higher levels of migration, invasion, and mammosphere formation, and had a greater proportion of cancer stem cells than PT. SCAF cells were highly enriched for gene expression signatures associated with metastasis and had associated genomic structural changes, including globally enhanced entropy. Collectively, our findings demonstrate that SCAF cells are distinct from PT and more closely resemble LUNG, indicating that tumor cells retrieved from scaffolds are reflective of cells at metastatic sites.

Monitoring metastatic events in distal tissues is challenged by their sporadic occurrence in obscure and inaccessible locations within these vital organs. A synthetic biomaterial scaffold can function as a synthetic metastatic niche to reveal the nature of these distal sites. These implanted scaffolds promote tissue ingrowth, which upon cancer initiation is transformed into a metastatic niche that captures aggressive circulating tumor cells. We hypothesized that immune cell phenotypes at synthetic niches reflect the immunosuppressive conditioning within a host that contributes to metastatic cell recruitment and can identify disease progression and response to therapy. We analyzed the expression of 632 immune-centric genes in tissue biopsied from implants at weekly intervals following inoculation. Specific immune populations within implants were then analyzed by single-cell RNA-seq. Dynamic gene expression profiles in innate cells, such as myeloid-derived suppressor cells, macrophages, and dendritic cells, suggest the development of an immunosuppressive microenvironment. These dynamics in immune phenotypes at implants was analogous to that in the diseased lung and had distinct dynamics compared with blood leukocytes. Following a therapeutic excision of the primary tumor, longitudinal tracking of immune phenotypes at the implant in individual mice showed an initial response to therapy, which over time differentiated recurrence versus survival. Collectively, the microenvironment at the synthetic niche acts as a sentinel by reflecting both progression and regression of disease. Significance: Immune dynamics at biomaterial implants, functioning as a synthetic metastatic niche, provides unique information that correlates with disease progression.