Charles Ruohua Liu

The consequence of lymphatic disruption during transplantation of solid organs remains unknown. Long-term survival after organ transplantation is limited by chronic rejection, a poorly understood process involving fibrotic remodeling and functional decline of the graft. Here, we found that transplanted human lungs and hearts with chronic rejection exhibited fibrosis distributed along dysmorphic lymphatics in areas densely concentrated with hyaluronan, an interstitial glycosaminoglycan that depends on lymphatic drainage for clearance. We illustrated similar findings in transplanted mouse lungs and hearts, which were accompanied by lymphographic findings of graft lymphedema. Using unsupervised clustering, we found a subset of stromal cells present in fibrotic syngeneic mouse lung grafts and human lung and heart grafts with chronic rejection that coexpressed hyaluronan synthase 1 and interleukin-1 receptor 1. Shortly after reperfusion of syngeneic mouse lung grafts, we identified neutrophilic expression of interleukin-1 β ( Il1b ) as a driver of hyaluronan synthase 1 up-regulation. We found interleukin-1–mediated hyaluronan accumulation as a mechanism driving fibrosis that occurred independent of alloimmunity in the setting of lymphatic disruption after transplantation. Development of fibrotic remodeling in transplanted mouse lungs was inhibited by preventing hyaluronan synthesis through the administration of 4-methylumbilliferone, accelerating lymphangiogenesis with pharmacologic activation of VEGF (vascular endothelial growth factor) receptor-3, or inhibiting interleukin-1 receptor 1 signaling in the graft. These therapeutic interventions lay the foundation for future clinical strategies to prevent chronic rejection.

A woman with a history of congenital heart disease status post multiple valve operations including mitral valve repair presented with 2 months of low back pain and general malaise. Blood cultures returned positive for Gram-positive cocci. While transthoracic echocardiography did not identify vegetations, transoesophageal echocardiography visualised vegetations on the patient’s mitral valve, which had previously undergone repair with annuloplasty. The patient was found to have infectious endocarditis (IE), caused by Gemella morbillorum. The patient was treated with over 6 weeks of intravenous antibiotics. Cases of Gemella-associated IE are rare and largely relegated to case reports. This report aims to contribute to the literature regarding this subject, and to further characterise the presentation and treatment of Gemella-associated IE. Additionally, this report emphasises the importance of maintaining a high suspicion of IE in a patient with non-specific malaise in the setting of prior cardiac valve operation.

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer-related mortality worldwide. A total of 20% of CRC patients present with distant metastases, most frequently to the liver and lung. In the primary tumor, as well as at each metastatic site, the cellular components of the tumor microenvironment (TME) contribute to tumor engraftment and metastasis. These include immune cells (macrophages, neutrophils, T lymphocytes, and dendritic cells) and stromal cells (cancer-associated fibroblasts and endothelial cells). In this review, we highlight how the TME influences tumor progression and invasion at the primary site and its function in fostering metastatic niches in the liver and lungs. We also discuss emerging clinical strategies to target the CRC TME.

Background: This is the first study to utilize the index of concentration at the extremes (ICE) to examine risk factors for spina bifida in Texas. The ICE is a useful measure for providing the degree to which residents in a certain area are concentrated into groups at the extremes of disadvantage and privilege. We introduce two novel ICE measures (language and nativity), and three existing ICE measures (race/ethnicity, income, and education), which we applied specifically to Texas residents.Methods: We used multivariable mixed‐model Poisson regression analyses to estimate spina bifida birth prevalence and prevalence ratios among singleton live births in Texas, 1999–2014, for each of our ICE measures. Maternal census tract at delivery was included in the models as a random effect. Analyses were stratified by maternal race/ethnicity (Hispanics and non‐Hispanic whites). Live births served as denominators for each category.Results: Among non‐Hispanic white women, those in the most disadvantaged versus the advantaged census tract quintile had adjusted relative risk between 1.6 and 8.5 for having a baby affected by spina bifida. However, Hispanic women in the most disadvantaged versus advantaged census tract quintile for four ICE measures had a 33% to 87% lower risk of having an affected pregnancy.Conclusions: Findings suggest spina bifida risk is associated with neighborhood disadvantage or advantage, and that relationship seems to vary by race‐ethnicity. The varied associations between ICE measures and spina bifida by race/ethnicity highlights the importance of using targeted interventions in the prevention of spina bifida.