A case of autoimmune enteropathy with CTLA4 haploinsufficiency

Autoimmune enteropathy (AIE) is a rare disease, characterized by intractable diarrhea, villous atrophy of the small intestine, and the presence of circulating anti-enterocyte autoantibodies. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, and mutations in FOXP3, which is a master gene of regulatory T cells (Tregs), are major causes of AIE. Recent studies have demonstrated that mutations in other Treg-associated genes, such as CD25 and CTLA4, show an IPEX-like phenotype. We present the case of a 13-year-old girl with CTLA4 haploinsufficiency, suffering from recurrent immune thrombocytopenic purpura and intractable diarrhea. We detected an autoantibody to the AIE-related 75 kDa antigen (AIE-75), a hallmark of the IPEX syndrome, in her serum. She responded well to a medium dose of prednisolone and a controlled dose of 6-mercaptopurine (6-MP), even after the cessation of prednisolone administration. Serum levels of the soluble interleukin-2 receptor and immunoglobulin G (IgG) were useful in monitoring disease activity during 6-MP therapy. In conclusion, autoimmune-mediated mechanisms, similar to the IPEX syndrome, may be involved in the development of enteropathy in CTLA4 haploinsufficiency. Treatment with 6-MP and monitoring of disease activity using serum levels of soluble interleukin-2 receptor and IgG is suggested for such cases.

Surgery for Bilateral Atrial Thromboses Detected in a Cancer Patient with Cerebral Infarction / 日本心臓血管外科学会雑誌

A 74-year-old man had been taking warfarin for atrial fibrillation, but warfarin was discontinued due to upper gastrointestinal bleeding. One week later, left hemiplegia occurred, and cranial magnetic resonance imaging revealed multiple cerebral infarctions. Systemic examination revealed thrombi in both atria as well as duodenal cancer. Because all of the thrombi in both atria were larger than 30 mm in diameter, the risk of embolism or sudden death was assumed to be high. Although the use of cardiopulmonary bypass for cancer patients is controversial, bilateral atrial thrombectomy was performed 4 weeks after cerebral infarction onset because reasonable survival duration was expected with surgery for duodenal cancer after thrombectomy and further treatment. The timing of and indications for surgery in this case are discussed.

Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer

The effects of first-line chemotherapy on overall survival [OS] might be confounded by subsequent therapies in patients with small cell lung cancer [SCLC]. We examined whether progression-free survival [PFS], post-progression survival [PPS], and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS [r = 0.97, p < 0.05, R[2] = 0.94], PFS was moderately correlated with OS [r = 0.58, p < 0.05, R[2] = 0.24], and tumor shrinkage was weakly correlated with OS [r = 0.37, p < 0.05, R[2] = 0.13]. The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS [p

Osseous Defects Seen in Patients with Anterior Shoulder Instability

Shoulder surgeons need to be aware of the critical size of the glenoid or humeral osseous defects seen in patients with anterior shoulder instability, since the considerable size of osseous defect is reported to cause postoperative instability. Biomechanical studies have identified the size of the osseous defect which affects stability. Since engagement always occurs between a Hill-Sachs lesion and the glenoid rim, when considering the critical size of the Hill-Sachs lesion, we have to simultaneously consider the size of the glenoid osseous defect. With the newly developed concept of the glenoid track, we are able to evaluate whether a large Hill-Sachs lesion is an "on-track" or "off-track" lesion, and to consider both osseous defects together. In case of an off-track Hill-Sachs lesion, if the glenoid defect is less than 25%, no treatment is required. In this case, the Latarjet procedure or arthroscopic remplissage procedure can be a treatment option. However, if the glenoid defect is more than 25%, treatment such as bone grafting is required. This will convert an off-track lesion to an on-track lesion. After the bone graft or Latarjet procedure, if the Hill-Sachs lesion persists as off-track, then further treatment is necessitated. In case with an on-track Hill-Sachs lesion and a less than 25% glenoid defect, arthroscopic Bankart repair alone is enough.