Organizing pneumonia following treatment with pembrolizumab for metastatic malignant melanoma - A case report.

Pembrolizumab is a monoclonal antibody against the programmed cell death 1 (PD-1) receptor, and is widely used for the treatment of various malignancies, most commonly malignant melanoma. Here we report the first documented and pathology proven case of Organizing Pneumonia complicating treatment with Pembrolizumab. This was a man who presented with a dense lung consolidation four months following treatment with Pembrolizumab. A thorough microbiological workup was negative and his findings did not improve with broad spectrum anti-microbial treatment. Transbronchial biopsy revealed organizing pneumonia, and treatment with cortico-steroids resulted in complete resolution of clinical and radiological disease. This report highlights the importance of recognizing immune related adverse events, specifically pulmonary inflammation, in patients receiving treatment with novel immune-modulating agents.

Lymphocytic interstitial pneumonia associated with common variable immunodeficiency resolved with intravenous immunoglobulins.

Lymphocytic interstitial pneumonia (LIP) is a rare form of interstitial lung disease. A few case reports have described an association with common variable immunodeficiency (CVID). Corticosteroids are usually used to treat symptomatic patients but their efficacy has never been studied in a controlled trial. We describe a patient with LIP and CVID who was treated monthly with intravenous immunoglobulins (IVIG) without steroids. The patient improved dramatically. We believe that, in selected cases of LIP and immunodeficiency, IVIG given monthly should be considered as the only treatment without adding steroids.

Rhinolalia as a presenting sign of pneumomediastinum complicating post peripheral blood stem cell transplantation bronchiolitis obliterans.

A 26-year-old male with graft vs. host disease (GVHD) presented with rhinolalia (a squeaky voice of nasal quality) as a presenting sign for pneumonasopharynx and pneumomediastinum secondary to bronchiolitis obliterans. The patient underwent HLA-identical related peripheral blood stem cells transplantation 8 months before the diagnosis. Three weeks after transplantation he began to suffer from GVHD Grade III that involved the gut, liver, and skin and later on the lungs. Due to severe obstructive bronchiolitis obliterans the patient developed intensive cough evolving into pneumomediastinum and pneumonasopharynx with rhinolalia. The patient was treated conservatively with complete resolution. Although rare, pneumomediastinum and pneumonasopharynx can be a life-threatening event, and one should be aware of the signs and symptoms on physical examination, which may be as subtle as rhinolalia alone.

The effect of enoxaparin on bleomycin-induced lung injury in mice.

We have evaluated the effect of enoxaparin, a potent antithrombotic drug, on bleomycin (Bleo)-induced pulmonary inflammation in mice. Pulmonary injury was induced by a single intratracheal (i.t.) instillation of Bleo. Four groups of female C57BL/6 mice, each received one of four treatments: (1) i.t. Bleo and daily intraperitoneal (i.p.) injections of enoxaparin (EN) starting one day before i.t. instillation of Bleo (Bleo-EN); (2) i.t. Bleo and i.p. injections of saline (Bleo-Sal); (3) i.t. saline and i.p. enoxaparin (Sal-EN); (4) i.t. saline and i.p. saline (Sal-Sal). Animals were sacrificed 14 days after i.t. treatment. Lung injury was evaluated by analysis of bronchoalveolar lavage fluid and histologically by an overall semiquantitative index of lung injury and a quantitative image analysis assessing alveolar wall area fraction and fibrosis fraction. Treatment of mice with enoxaparin did not ameliorate Bleo-induced lung injury. Our study does not establish a critical role of procoagulant activity in the evolution of Bleo-induced lung injury and does not support the use of antithrombotic therapy for the prevention of pulmonary fibrosis.

Dopaminergic denervation reverses behavioral deficits induced by prenatal exposure to phenobarbital.

Mice were prenatally exposed to phenobarbital. As adults, these mice (B animals) were deficient in the hippocampally related eight-arm maze performance, a behavior apparently dependent on the integrity of the septohippocampal cholinergic pathways. Preliminary studies suggest possible parallel alterations in their hippocampal cholinergic innervations. The dopaminergic septal innervations are known to indirectly inhibit the septohippocampal cholinergic innervations. Consequently, the septal dopaminergic innervations of adult B mice were destroyed by 6-hydroxydopamine (6-OHDA). Mice treated with 6-OHDA had an improvement in maze performance which was most marked with increased experience. Concomitant increase in choline acetyltransferase (ChAT) was also demonstrated in these mice (79%, P less than 0.001). Similar increase in ChAT could be demonstrated in control mice after 6-OHDA treatment, but the behavioral changes were small and did not reach statistical significance, possibly due to the ceiling effect of the studied behavior. Thus, the dopaminergic innervations in the septum regulate cholinergic activity and its related behaviors along the septohippocampal pathway, and thereby ameliorate behavioral deficits induced by early phenobarbital administration.