A 75-year-old man with no significant past medical history presented with a 3-week period of fever, fatigue, and a 7-kg weight loss. Physical examination revealed a poor performance status (PS; Eastern Cooperative Oncology Group score 3), emaciation, and anemia of palpebral conjunctiva. Laboratory data included a WBC count of 15.7 K/L, moderate anemia (hemoglobin concentration of 7.2 g/dL), and a platelet count of 757 K/L. Serum chemistry showed total protein, albumin, and C-reactive protein (CRP) of 8.5 g/dL, 1.7 g/dL (␥globulin was 50% in the protein fraction), and 24.51 mg/dL, respectively. In addition, serum immunoglobulin G was increased (4.3 g/dL) as was interleukin-6 (IL-6; 172 pg/mL). A computed tomography (CT) scan of the thorax showed a 3-cm mass in the right hilum and swelling of mediastinal lymph nodes, although there was no evidence of metastasis in remote organs. Accordingly, we considered a differential diagnosis of lung cancer, Castleman's disease, or tuberculosis. Subsequent endobronchial ultrasound-guided transbronchial needle aspiration resulted in the detection of a large-cell carcinoma and a final diagnosis of primary lung cancer at clinical stage T2aN2M0 (stage IIIA) with cancer cachexia.Because it was difficult to start chemotherapy and radiotherapy as a result of the poor PS of the patient, we started prednisolone 0.5 mg/kg (a total of 30 mg) for cachexia. After 2 weeks, his symptoms and PS diminished slightly including a decrease of serum IL-6 level to 112 mg/mL. Consequently, we performed systemic chemotherapy (pemetrexed 500 mg/m 2 once every 3 weeks, two courses) and sequential radiotherapy. These treatments produced no adverse events and were completed. However, the PS of the patient deteriorated to an Eastern Cooperative Oncology Group score of 4, with a decrease in serum albumin to 0.8 g/dL as a result of the recurrence of cancer cachexia and an increase of the serum IL-6 level to 173 pg/mL. Accordingly, we diagnosed his condition as progressive cancer cachexia, which was resistant to treatment with prednisolone, and realized that supportive care is usually considered the best choice of treatment. However, on the basis of the clinical findings, we theorized that the cachexia might be controlled by inhibiting the IL-6 mediated inflammatory response with tocilizumab anti-IL-6 receptor antibody. After approval by the institutional review boards of our institution, agreement by the patient and his family, and receipt of a written informed consent, we began tocilizumab therapy for the patient at 8 mg/kg (a total of 400 mg) every 4 weeks.Soon after this treatment began, the symptoms of the patient rapidly lessened, his appetite improved, and his CRP levels normalized in 2 weeks (Table 1). His overall physical condition recovered enough so that he could walk short distances after 4 weeks; after 8 weeks, he was able to live at home without nursing support. The body weight and albumin level of the patient improved dramatically to 46 kg (from

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Reduced enhancements of bowel wall and mesenteric veins were good indicators of bowel ischemia or necrosis. On the contrary, engorgement of the mesenteric veins was a predictor of a viable bowel.

A disruption of immune checkpoints leads to imbalances in immune homeostasis, resulting in immune-related adverse events. Recent case studies have suggested the association between immune checkpoint inhibitors (ICIs) and the disorders of the coagulation-fibrinolysis system, implying that systemic immune activation may impact a balance between clotting and bleeding. However, little is known about the association of coagulation-fibrinolysis system disorder with the efficacy of ICIs. We retrospectively evaluated 83 lung cancer patients who received ICI at Kumamoto University Hospital. The association between clinical outcome and diseases associated with disorders of the coagulation-fibrinolysis system was assessed along with tumor PD-L1 expression. Among 83 NSCLC patients, total 10 patients (12%) developed diseases associated with the disorder of coagulation-fibrinolysis system. We found that disorders of the coagulation-fibrinolysis system occurred in patients with high PD-L1 expression and in the early period of ICI initiation. In addition, high tumor responses (72%) were observed, including two complete responses among these patients. Furthermore, we demonstrate T-cell activation strongly induces production of a primary initiator of coagulation, tissue factor in peripheral PD-L1high monocytes, in vitro. This study suggests a previously unrecognized pivotal role for immune activation in triggering disorders of the coagulation-fibrinolysis system in cancer patients during treatment with ICI.

ObjectivesTo quantify the risk of pneumococcal pneumonia (PP) and invasive pneumococcal disease (IPD) in adults aged ≥19 years with underlying medical conditions compared with healthy adults of the same age in Japan.DesignAn observational, retrospective, cohort study using two healthcare claims databases in Japan: Japan Medical Data Center (JMDC) and Medical Data Vision (MDV) databases.ParticipantsA total of 10.4 million individuals, representing 9.3 million person-years of follow-up, were included in the analysis. Eleven medical conditions as well as PP and IPD were identified by the International Statistical Classification of Diseases and Related Health Problems version 10 diagnostic codes and/or local disease codes used in Japan.Primary outcome measuresAdjusted rate ratios (RRs) for PP and IPD in adults with a medical condition versus adults without any medical condition were calculated using multivariate Poisson regression models with age and/or sex as covariates.ResultsIn the JMDC and MDV databases, respectively, adults ≥19 years with a medical condition (RRs for PP: 3.3 to 13.4, 1.7 to 5.2; RRs for IPD: 12.6 to 43.3, 4.4 to 7.1), adults with two or more medical conditions (PP: 11.6, 2.8; IPD: 18.7, 5.8) and high-risk adults (PP: 12.9, 1.8; IPD: 29.7, 4.0) were at greater risk of PP and IPD compared with their healthy counterparts. Adults aged 50–64 years with an underlying medical condition (PP rate: 38.6 to 212.1 per 100 000 person-years) had a higher rate of PP than those aged ≥65 years without any condition (PP rate: 13.2 to 93.0 per 100 000 person-years).ConclusionsAdults of all ages with an underlying medical condition are at greater risk of PP and IPD compared with adults without any medical condition. This risk increases with the number of underlying medical conditions. Our results support extending pneumococcal vaccination to younger adults with an underlying medical condition, especially those aged 50–64 years.