Gastroesophageal Reflux Disease in a One-Week-Old Infant Presenting With Cyanosis and Respiratory Distress.

Gastroesophageal reflux (GER) is a common occurrence in infancy and early childhood. While GER is considered physiologic, gastroesophageal reflux disease (GERD) can result when extensive GER leads to troublesome symptoms such as choking, gagging, vomiting, refusal to feed, and poor weight gain. In extreme cases, GERD can cause severe respiratory complications such as apnea and aspiration pneumonia. We present the case of a one-week-old Amish female who had no prenatal care and presented with severe hypoxemia, tachypnea, and costal retractions. Further history from the family revealed persistent irregular breathing, sweating during feeds, and episodic perioral cyanosis. The patient required stabilization in the intensive care unit and received an extensive workup to rule out sepsis, cyanotic heart disease, other infectious etiologies, and other common causes of respiratory distress. The patient underwent a modified barium swallow study and was diagnosed with aspiration pneumonitis resulting from GERD and oropharyngeal dysphagia. Infantile cyanosis and respiratory distress can be manifestations of a variety of underlying illnesses. Once common causes of cyanosis have been excluded, GERD or disordered feeding should be considered as a potential etiology.

Inducing regulated necrosis and shifting macrophage polarization with anti-EMMPRIN antibody (161-pAb) and complement factors.

Treatment of solid tumors is often hindered by an immunosuppressive tumor microenvironment (TME) that prevents effector immune cells from eradicating tumor cells and promotes tumor progression, angiogenesis, and metastasis. Therefore, targeting components of the TME to restore the ability of immune cells to drive anti-tumoral responses has become an important goal. One option is to induce an immunogenic cell death (ICD) of tumor cells that would trigger an adaptive anti-tumoral immune response. Here we show that incubating mouse renal cell carcinoma (RENCA) and colon carcinoma cell lines with an anti-extracellular matrix metalloproteinase inducer polyclonal antibody (161-pAb) together with complement factors can induce cell death that inhibits caspase-8 activity and enhances the phosphorylation of receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase-like domain (MLKL). This regulated necrotic death releases high levels of dsRNA molecules to the conditioned medium (CM) relative to the necrotic death of tumor cells induced by H2 O2 or the apoptotic death induced by etoposide. RAW 264.7 macrophages incubated with the CM derived from these dying cells markedly enhanced the secretion of IFNß, and enhanced their cytotoxicity. Furthermore, degradation of the dsRNA in the CM abolished the ability of RAW 264.7 macrophages to secrete IFNß, IFNγ-induced protein 10 (IP-10), and TRAIL. When mice bearing RENCA tumors were immunized with the 161-pAb, their lysates displayed elevated levels of phosphorylated RIPK3 and MLKL, as well as increased concentrations of dsRNA, IFNß, IP-10, and TRAIL. This shows that an antigen-targeted therapy using an antibody and complement factors that triggers ICD can shift the mode of macrophage activation by triggering regulated necrotic death of tumor cells.