Incidence and risk factors for respiratory tract bacterial colonization and infection in lung transplant recipients.

To evaluate incidence of and risk factors for respiratory bacterial colonization and infections within 30 days from lung transplantation (LT). We retrospectively analyzed microbiological and clinical data from 94 patients transplanted for indications other than cystic fibrosis, focusing on the occurrence of bacterial respiratory colonization or infection during 1 month of follow-up after LT. Thirty-three percent of patients developed lower respiratory bacterial colonization. Bilateral LT and chronic heart diseases were independently associated to a higher risk of overall bacterial colonization. Peptic diseases conferred a higher risk of multi-drug resistant (MDR) colonization, while longer duration of aerosol prophylaxis was associated with a lower risk. Overall, 35% of lung recipients developed bacterial pneumonia. COPD (when compared to idiopathic pulmonary fibrosis, IPF) and higher BMI were associated to a lower risk of bacterial infection. A higher risk of MDR infection was observed in IPF and in patients with pre-transplant colonization and infections. The risk of post-LT respiratory infections could be stratified by considering several factors (indication for LT, type of LT, presence of certain comorbidities, and microbiologic assessment before LT). A wider use of early nebulized therapies could be useful to prevent MDR colonization, thus potentially lowering infectious risk.

The insulin resistance Grb14 adaptor protein promotes thyroid cancer ret signaling and progression.

The growth factor receptor-bound protein (Grb) 14 is an adaptor molecule of the Grb7/10/14 family with characteristic Between Plekstrin and SH2 (BPS) domains serving to avidly bind tyrosine kinases. Grb14 inhibits insulin receptor (IR) catalytic activity through interaction with the BPS domain and impedes peptide substrate binding. Members of this Grb family have also been shown to interact with other kinases through their SH2 domain. Here we examined the functional role of Grb14 in thyroid cancer using loss- and gain-of-function approaches. Stable knockdown of Grb14 in thyroid cancer cells facilitated IR signaling. In contrast, RET phosphorylation was diminished in concert with reduced activation of Akt and signal transducer and activator of transcription 3 (STAT3). Loss of Grb14 also resulted in diminished cell proliferation and invasion both in vitro and in mouse flank xenografts. In complementary studies, forced expression of Grb14 interrupted IR signaling but facilitated RET activation, STAT3 and Akt phosphorylation. Consistent with these findings Grb14 overexpression enhanced cell invasion and resulted in striking metastases in an orthotopic thyroid cancer mouse xenograft model. Primary human thyroid cancer microarrays revealed a positive correlation between Grb14 expression and invasive behavior. Our findings uncover a new role for Grb14 in finely tuning receptor signaling and modulating thyroid cancer progression.