mmune checkpoint inhibitors activate anti-tumor defenses either through the disruption of inhibitory interactions between antigen-presenting cells and T lymphocytes at so-called checkpoints (anti-PD-1/PD-L1, anti-CTLA-4, anti-TIM-3, anti-LAG-3) or else through the stimulation of activating checkpoints (CD27, CD40, GITR, CD137). They are now used to treat various types of cancer, including lung cancer, renal cell carcinoma, Merkel cell carcinoma, Hodgkin's lymphoma, and urothelial carcinoma (eTable) and special groups of patients, e.g., patients with microsatellite instability (1). In patients with metastatic melanoma, the anti-CTLA-4 antibody ipilimumab, the anti-PD-1 antibodies nivolumab and pembrolizumab, and combination therapy with ipilimumab and an anti-PD-1 antibody can prolong survival and induce response rates of 19% (2), 36-44% (2, 3), and 58-61% (2, 4), respectively. Severe and even life-threatening side effects (classified according to the Common Terminology Criteria for Adverse Events" [CTCAE]; grade 3/4) arise in 17-21% of patients receiving anti-PD-1 monotherapy (2, 3), 20-28% of those receiving ipilimumab (2, 3), 45% of those receiving ipilimumab (1 mg/kg) plus pembrolizumab (4), and 59% of those receiving approved combination therapy with ipilimumab (3 mg/kg) and nivolumab (2) (Table 1). Immune checkpoint inhibitors often induce autoimmune side effects, which can affect all organ systems. These differ from the corresponding spontaneously occurring autoimmune diseases in many ways, including phenotypically, histologically, and serologically. The mechanisms of autoimmune side effects include the activation of T lymphocytes with infiltration of the organ in question (5), direct binding of the checkpoint inhibitor with activation of complement (CTLA-4 expression in the pituitary gland) (6), and immune reactions due to soluble factors (autoantibodies, cytokines). Moreover, the intestinal microbiome seems to influence the development of side effects (7, 8). No predictive factors for the appearance of side effects have yet been identified. Common side effects include colitis, hepatitis, skin reactions, and endocrinopathies (thyroiditis or hypophysitis); rarer ones are myositis, cardiomyositis, and neurological side effects. The side effects are usually readily controllable. Checkpoint inhibitor treatment must be discontinued because of side effects in 7-12% of patients receiving anti-PD-1 therapy, 9-16% of those receiving ipilimumab therapy (2, 3), and 39% of those receiving combination therapy (2).

Disseminated infection with Aspergillus terreus is a rare disease that affects only the immunocompromised host. We report a case of systemic infection with A. terreus resulting in endocarditis, aortic embolization, and splenic infarction in a patient with acute lymphoblastic leukemia. Diagnosis through peripheral blood culture, lack of pulmonary involvement, and onset of disease during complete remission from leukemia constitute uncommon features of this case.

Induction of factor VIII (FVIII) inhibitors sometimes occurs in patients with hemophilia due to frequent supplementation of FVIII. The inhibitor is rarely detected in non-hemophilic patients; however, an association has been described in patients with chronic inflammatory diseases, such as autoimmune diseases (e.g. SLE and rheumatoid arthritis), malignant tumors and drug allergies, and also to pregnant or aged individuals without underlying disease. We report on an 82-year-old patient who was transferred to our hospital after the diagnosis of acquired FVIII inhibitor. On admission the laboratory results showed no detectable FVIII activity (0%, normal range 70-100%), prolongation of coagulation time (APTT 102.4 s), and severe anemia 7.8 g/dL (normal range 12-16 g/dL). On physical examination multiple subcutaneous hematomas were detected and further bleeding in his left pectoralis muscle was observed. Despite extensive investigation no underlying disease was detected. Thirty-six courses of plasma exchange with 360 units of fresh frozen plasma replacement daily were conducted. High dose steroids and mycophenolate mofetil (MMF) were given throughout the course, and cyclophosphamide was administered once. Thirty-four units of erythrocytes were applied during this time. After 36 courses of plasma exchange in combination with high dose steroids, FVIII activity and coagulation time normalized and bleeding could be stopped. The patient was discharged in good health 48 days after admission. Hence, we present a case of severe idiopathic FVIII inhibitor-positive hemophilia successfully treated with the combination of plasma exchange, corticosteroids, cyclophosphamide and MMF.

The authors regret that an error appeared in their original version of Fig. 4. Some of the PE and PS species listed on the x axis of Fig. 4 B were incorrect. The corrected figure and corresponding legend appear below.The online HTML and PDF versions of this paper have been corrected. The error remains only in the print version. -dependent externalization of aminophospholipids (APL) at the surface of eosinophils. OH indicates hydroxyl group. Data are representative of at least three independent experiments. Error bars represent SEM. *, P < 0.05; ***, P < 0.001. Cor rection

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