Contribution of Puma to Inflammatory Resolution During Early Pneumococcal Pneumonia.

Apoptosis of cells at the site of infection is a requirement for shutdown of inflammatory signaling, avoiding tissue damage, and preventing progression of sepsis. Puma+/+ and Puma-/- mice were challenged with TIGR4 strain pneumococcus and cytokines were quantitated from lungs and blood using a magnetic bead panel analysis. Puma-/- mice exhibited higher lung and blood cytokine levels of several major inflammatory cytokines, including IL-6, G-CSF, RANTES, IL-12, IFN-ϒ, and IP-10. Puma-/- mice were more susceptible to bacterial dissemination and exhibited more weight loss than their wild-type counterparts. RNA sequencing analysis of whole pulmonary tissue revealed Puma-dependent regulation of Nrxn2, Adam19, and Eln. Enrichment of gene ontology groups differentially expressed in Puma-/- tissues were strongly correlated to IFN-ß and -ϒ signaling. Here, we demonstrate for the first time the role of Puma in prohibition of the cytokine storm during bacterial pneumonia. These findings further suggest a role for targeting immunomodulation of IFN signaling during pulmonary inflammation. Additionally, our findings suggest previously undemonstrated roles for genes encoding regulatory and binding proteins during the early phase of the innate immune response of pneumococcal pneumonia.

Gram stain to the rescue: a case report of cerebral phaeohyphomycosis by Cladophialophora bantiana in an immunocompetent 24-year-old.

BACKGROUND: Fungal brain abscesses in immunocompetent patients are exceedingly rare. Cladophialophora bantiana is the most common cause of cerebral phaeohyphomycosis, a dematiaceous mold. Radiological presentation can mimic other disease states, with diagnosis through surgical aspiration and growth of melanized fungi in culture. Exposure is often unknown, with delayed presentation and diagnosis. CASE PRESENTATION: We present a case of cerebral phaeohyphomycosis in a 24-year-old with no underlying conditions or risk factors for disease. He developed upper respiratory symptoms, fevers, and headaches over the course of 2 months. On admission, he underwent brain MRI which demonstrated three parietotemporal rim-enhancing lesions. Stereotactic aspiration revealed a dematiaceous mold on staining and the patient was treated with liposomal amphotericin B, 5-flucytosine, and posaconazole prior to culture confirmation. He ultimately required surgical excision of the brain abscesses and prolonged course of antifungal therapy, with clinical improvement. CONCLUSIONS: Culture remains the gold standard for diagnosis of infection. Distinct microbiologic findings can aid in identification and guide antimicrobial therapy. While little guidance exists on treatment, patients have had favorable outcomes with surgery and combination antifungal therapy. In improving awareness, clinicians may accurately diagnose disease and initiate appropriate therapy in a more timely manner.

Brodifacoum Inhalation and its Clinical Manifestations in a 21-Year-Old Caucasian Man.

Exposure to brodifacoum, a superwarfarin substance, can lead to severe coagulopathic manifestations. Brodifacoum is a lipophilic, vitamin K antagonist with a long half-life. Clinical manifestations are challenging to diagnose if the patient cannot provide information regarding exposure. Herein, we report the first case in the literature, to our knowledge, of a patient who had intentionally inhaled brodifacoum. We performed coagulation studies such as prothrombin time (PT) and international normalized ratio (INR) to monitor vitamin K dependent coagulation factors in the patient, a 21-year-old Caucasian man. On admission to the hospital, the INR of the patient was 12.9; a computed tomography (CT) angiogram detected a mediastinal hemorrhage. In the absence of 4-factor PCC, the patient received 30 plasma transfusions during a 4-day period due to persistent left pleural effusions, along with vitamin K therapy to normalize his coagulation factors. His high-performance liquid chromatography (HPLC) results on hospital day 3 and day 26 confirmed the presence of brodifacoum in his body. We believe that inhalation led the poison to bypass the initial metabolism process of the liver, resulting in rapid anticoagulation and subsequent bleeding diathesis. Management of brodifacoum poisoning is case dependent on the amount of exposure and INR status. Constant INR monitoring, large dose vitamin K therapy and initial plasma transfusions (in the absence of PCC) were able to prevent severe internal bleeding in the patient.