The innate immune response to lower respiratory tract E. Coli infection and the role of the CCL2-CCR2 axis in neonatal mice.

Neonates have greater morbidity/mortality from lower respiratory tract infections (LRTI) compared to older children. Lack of conditioning of the pulmonary immune system due to limited environmental exposures and/or infectious challenges likely contributes to the increase susceptibility in the neonate. In this study, we sought to gain insights into the nature and dynamics of the neonatal pulmonary immune response to LRTI using a murine model. METHODS: Wildtype (WT) and Ccr2-/- C57BL/6 neonatal and juvenile mice received E. coli or PBS by direct pharyngeal aspiration. Flow cytometry was used to measure immune cell dynamics and identify cytokine-producing cells. Real-time PCR and ELISA were used to measure cytokine/chemokine expression. RESULTS: Innate immune cell recruitment in response to E. coli-induced LRTI was delayed in the neonatal lung compared to juvenile lung. Lung clearance of bacteria was also significantly delayed in the neonate. Ccr2-/- neonates, which lack an intact CCL2-CCR2 axis, had higher mortality after E. coli challenged than Ccr2+/+ neonates. A greater percentage of CD8+ T cells and monocytes from WT neonates challenged with E. coli produced TNF compared to controls. CONCLUSION: The pulmonary immune response to E. coli-induced LRTI differed significantly between neonatal and juvenile mice. Neonates were more susceptible to increasing doses of E. coli and exhibited greater mortality than juveniles. In the absence of an intact CCL2-CCR2 axis, susceptibility to LRTI-induced mortality was further increased in neonatal mice. Taken together these findings underscore the importance of age-related differences in the innate immune response to LRTI during early stages of postnatal life.

Incidence, reasons, and risk factors for readmission after surgery for benign distal esophageal disease.

BACKGROUND: Our aim was to ascertain the incidence of, reasons for, and risk factors associated with hospital readmission after an operation for benign distal esophageal disease. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database (2012-2014), patients with a primary diagnosis of gastroesophageal reflux disease, paraesophageal hiatal hernia, or achalasia who underwent fundoplication, paraesophageal hernia repair, or Heller myotomy were identified. The primary outcome was hospital readmission. Multivariable logistic regression analysis was used to identify risk factors associated with hospital readmission. RESULTS: Of the 14,478 patients included in this study, 801 (5.5%) were readmitted at a median of 11 days (interquartile range 6-17) postprocedure. Intolerance of oral intake (21.8%), respiratory complications (11.6%), abdominal pain (6.0%), and venous thromboembolic events (4.7%) were some of the most common reasons for readmission. Open operative approach (odds ratio 1.34, 95% confidence interval 1.05-1.71), chronic steroid use (odds ratio 1.48, 95% confidence interval 1.10-2.00), emergency admission (odds ratio 1.50, 95% confidence interval 1.01-2.21), and predischarge complication (odds ratio 1.91, 95% confidence interval 1.42-2.59) were associated most strongly with hospital readmission. CONCLUSION: Implementing standardized perioperative strategies, such as nutritional counseling, early ambulation, intensive pulmonary toilet, and deep vein thrombosis prophylaxis, may help decrease the number of preventable readmissions and enhance the overall quality of care in this patient population.

Recruited monocytes modulate malaria-induced lung injury through CD36-mediated clearance of sequestered infected erythrocytes.

Pulmonary complications occur in a significant percentage of adults and children during the course of severe malaria. The cellular and molecular innate immune mechanisms that limit the extent of pulmonary inflammation and preserve lung function during severe Plasmodium infections remain unclear. In particular, the contributions to pulmonary complications by parasitized erythrocyte sequestration and subsequent clearance from the lung microvasculature by immune cells have not been clearly defined. We used the Plasmodium berghei ANKA-C57BL/6 mouse model of severe malaria to investigate the mechanisms governing the nature and extent of malaria-associated lung injury. We have demonstrated that sequestration of infected erythrocytes on postcapillary endothelial surfaces results in acute lung injury and the rapid recruitment of CCR2(+)CD11b(+)Ly6C(hi) monocytes from the circulation. These recruited cells remain in the lungs as monocyte-derived macrophages and are instrumental in the phagocytic clearance of adherent Plasmodium berghei-infected erythrocytes. In contrast, alveolar macrophages do not play a significant role in the clearance of malaria-infected cells. Furthermore, the results obtained from Ccr2(-/-), Cd36(-/-), and CD36 bone marrow chimeric mice showed that sequestration in the absence of CD36-mediated phagocytic clearance by monocytes leads to exaggerated lung pathologic features. In summary, our data indicate that the intensity of malaria-induced lung pathologic features is proportional to the steady-state levels of Plasmodium-infected erythrocytes adhering to the pulmonary vasculature. Moreover, the present work has defined a major role of recruited monocytes in clearing infected erythrocytes from the pulmonary interstitium, thus minimizing lung damage.

Does Quality of Care Matter? A Study of Adherence to National Comprehensive Cancer Network Guidelines for Patients with Locally Advanced Esophageal Cancer.

INTRODUCTION: The aim of this study was to assess whether adherence to National Comprehensive Cancer Network (NCCN) guidelines leads to differences in survival in patients diagnosed with locally advanced esophageal cancer. METHODS: This is a retrospective cohort study of patients with stage II and III esophageal cancer included in the Cancer Registry at the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Hospital from 2008 to 2013. Seven quality indicators were identified using the 2014 NCCN guidelines, and individual and overall quality measure scores were calculated and used to define low and high quality of care groups. RESULTS: One hundred forty-one patients met inclusion criteria, and 88 patients (62.4 %) were identified as receiving high-quality care. Adherence to guidelines ranged from 63.1 to 100.0 %, with an overall compliance of 81.3 %. Risk factors for receiving low quality of care included advanced age, non-white race, lower education level, and unspecified primary site of tumor. A significantly better overall survival was observed in patients who received high-quality care (HR, 0.58; 95 %, 0.37-0.90, p = 0.015). CONCLUSIONS: Delivery of high-quality care is associated with improved survival in these patients. Efforts should be directed at minimizing disparities in treatment in regards to race and educational levels.

Hydraulic testing of intravascular axial flow blood pump designs with a protective cage of filaments for mechanical cavopulmonary assist.

To provide hemodynamic support to patients with a failing single ventricle, we are developing a percutaneously inserted, magnetically levitated axial flow blood pump designed to augment pressure in the cavopulmonary circulation. The device is designed to serve as a bridge-to-transplant, bridge-to-recovery, bridge-to-hemodynamic stability, or bridge-to-surgical reconstruction. This study evaluated the hydraulic performance of three blood pump prototypes (a four-bladed impeller, a three-bladed impeller, and a three-bladed impeller with a four-bladed diffuser) whose designs evolved from previous design optimization phases. Each prototype included the same geometric protective cage of filaments, which stabilize the rotor within the housing and protect the housing wall from the rotating blades. All prototypes delivered pressure rises over a range of flow rates and rotational speeds that would be sufficient to augment hemodynamic conditions in the cavopulmonary circulation. The four-bladed impeller outperformed the two remaining prototypes by >40%; this design was able to generate a pressure rise of 4-28 mm Hg for flow rates of 0.5-10 L/min at rotational speeds of 4,000-7,000 RPM. Successful development of this blood pump will provide clinicians with a feasible therapeutic option for mechanically supporting the failing Fontan.