Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH). The prognosis of PVOD patients remains poor, since no effective medical therapy is yet available. Imatinib is a tyrosine kinase inhibitor specific for platelet-derived growth factor receptor and is expected as a treatment option for pulmonary arterial hypertension (PAH). Recently, it has been reported that imatinib improved functional capacity of a patient with PVOD. We here report a patient with suspected PVOD who has been successfully treated with imatinib and is alive for 6 years after diagnosis. A 57-year-old woman was admitted to a hospital for severe dyspnea. Echocardiography suggested the presence of PH, because tricuspid regurgitation pressure gradient was elevated. The patient was then transferred to our hospital by an ambulance ahead of schedule due to fever and worsening dyspnea. Because the patient had no left heart disease, we diagnosed that she had PAH associated with severe right heart failure. We immediately started treatment with nitric oxide (NO) for her severe hypoxia; however, it caused pulmonary edema. We suspected PVOD from CT characteristics and pulmonary edema after PAH-targeted vasodilator therapy, and then started oral imatinib treatment. In response to imatinib, her pulmonary edema gradually improved. Since then, the patient has been alive for 6 years with imatinib and pulmonary vasodilators. At present, lung transplantation is the only effective therapy for PVOD with limited availability. We therefore propose that imatinib may be a treatment option for PVOD and a bridge to lung transplantation.
Bisphosphonates (BPs) have been used as antiresorptive agents to treat patients with osteoporosis or metastatic bone cancer, each of which is characterized by bone loss due to the increased bone resorption. However, BPs could cause osteonecrosis of the jaw (ONJ), known as bisphosphonate-related osteonecrosis of the jaw (BRONJ). ONJ is associated with severe pain and deteriorated quality of life. ONJ is also caused by administration of denosumab, a monoclonal antibody against receptor activator of NFκB ligand (RANKL), that functions as a powerful antiresorptive agent. Accordingly, antiresorptive agent-related ONJ (ARONJ) has been advocated, the incidence of which is continuing to increase in Japan as a super-aging society. Importantly, the jawbone is more susceptible to infection compared with bones in other parts of the body, due to the unique anatomical and physiological characteristics; for example, the jawbone with a high remodeling rate is stimulated by teeth during mastication. The risk factors of ARONJ include dental infection, poor occlusal or oral hygiene status, and bone-invasive dental treatment, such as tooth extraction, dental implants, and dentures. Proper collaboration between doctors and dentists is of utmost importance to understand the current status of ARONJ and prevent developing ARONJ. It is also important to ensure that the patients treated with BPs or denosumab can receive appropriate dental treatment. More recently, angiogenesis inhibitors were reported to cause ONJ; thus, medication-related ONJ (MRONJ) has been advocated. This article overviews the concept of MRONJ by focusing on antiresorptive agents and the status of BRONJ in Japan.
Ocular neovascular diseases are featured by abnormal angiogenesis in the eye, and they seriously threaten the human visual health. These diseases include proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), retinopathy of prematurity (ROP), and retinal vein occlusion (RVO). In fact, ocular neovascular diseases represent the leading causes of vision impairment and blindness worldwide. Ocular neovascularization, the process of pathological vessel formation in eye, underlies ocular neovascular diseases. Cytokines have important regulatory roles in neovascularization through immunological networks. Interleukin (IL)-17, the signature cytokine produced by T helper 17 (Th17) cells, has proven to be involved in ocular neovascularization. However, roles of IL-17 in ocular neovascular diseases still remain controversial. This review provides an overview of the functional roles of IL-17 in ocular neovascular diseases from basic research to clinical evidence by focusing on PDR, AMD, ROP, and RVO. The possible roles of IL-17 in neovascularization are achieved through a regulatory network of cytoskeleton remodeling, vascular endothelial growth factor (VEGF), VEGF-related cytokines, and complement components. Current applications as well as potential therapies targeting IL-17 with genome editing systems are also outlined and discussed. Targeting IL-17 might be a promising therapeutic strategy against ocular neovascular diseases.
Although cigarette smoking is a major risk factor for lung cancer, genetic susceptibility may also affect lung cancer risk. To explore the role of genetic risk, this case-control study investigated the association between family history of cancer at several sites and lung cancer risk. A total of 1,733 lung cancer cases and 6,643 controls were selected from patients aged 30 years and over admitted to a single hospital in Japan between 1997 and 2009. Information on family history of cancer was collected using a self-administered questionnaire and odds ratios (ORs) were estimated by unconditional logistic regression. Family history of lung cancer in first-degree relatives was associated with an increased risk of lung cancer among both sexes. According to histology and type of relatives, a parental history of lung cancer was significantly associated with an increased risk of female adenocarcinoma (OR = 1.72). Stratification by smoking status revealed that this significant positive association in women was limited to ever-smokers (OR = 4.13). In men, a history of lung cancer in siblings was significantly associated with an increased risk of small cell carcinoma (OR = 2.28) and adenocarcinoma (OR = 2.25). Otherwise, positive associations between history of breast (OR = 1.99) and total (OR = 1.71) cancers in siblings and the risk of male adenocarcinoma were observed. These results suggest that inherited genetic susceptibility may contribute to the development of lung cancer. In men, shared exposure to environmental factors among siblings may also be responsible for the increase in lung cancer risk.
Early initiation of enteral nutrition improves clinical outcomes in critical patients with serious burns. Post-pyloric tube feeding is a valuable therapeutic option for severely burned patients with poor gastric emptying. How early post-pyloric feeding can be initiated to provide more benefits to patients has not yet been examined. A fire erupted at a recreational water park in New Taipei City, Taiwan, on June 27, 2015. The results of early initiation versus delayed post-pyloric feeding in severely burned patients in this mass-casualty incident were compared. Door-to-post-pyloric feeding time ≤ 24 h was considered as early post-pyloric feeding (EPF) and that > 24 h was considered as delayed post-pyloric feeding (DPF). Thirteen patients with severe burn injuries (> 40% of the total body surface area) were assigned to undergo either EPF (five patients) or DPF (eight patients). This study is a “fortuitously controlled” study, and the authors were able to formulate and test whether EPF is better than DPF by comparing the two groups. In patients in the EPF, the intake of calories increased rapidly and was maintained throughout the study period. In addition, rapid restoration of plasma magnesium concentrations as well as pronounced recovery of platelet count in the EPF group was observed. In conclusion, our findings indicate that the time from injury to the onset of post-pyloric feeding is crucial, and EPF allows for the administration of calculated caloric needs. Therefore, EPF can be successfully initiated with beneficial outcomes of nutritional reconstruction in severely burned patients.
Epithelioid angiomyolipoma (EAML) has been known as a potentially malignant tumor which occasionally recur and/or metastasize to other organs, and clinically and pathologically recognized as distinct entity. However, the mechanisms of recurrence and/or metastasis (recurrence/metastasis) has still remained unknown. Here, we report two cases of renal EAML associated with recurrence/metastasis, and three cases of EAML in kidney or liver without recurrence/metastasis. According to the previous histological predictive models of EAML, the primary tumor was classified as low risk group in one of the cases with recurrence/metastasis in spite of its malignant behavior. Therefore, we considered that further investigation about the mechanisms of recurrence/metastasis in EAML is required for a malignancy prediction. We focused on some cell-cycle modulators, including mouse double minute 2 homolog (MDM2), which is ubiquitin ligase well-known to promote malignant behaviors by p53 ubiquitination and degradation, and also other cellular processes including genomic instability and epithelial-mesenchymal transition in p53-independent manners in various human malignancies. Immunohistochemical evaluation revealed that MDM2 protein expression increased stepwise throughout every steps of metastasis/recurrence in both cases, although it was negative in primary tumors. In conclusion, this is the first study demonstrating that MDM2 could play an important role in the molecular mechanisms of recurrence/metastasis of EAML. Further analyses focusing on MDM2 pathway could contribute to the identification of novel prognostic factors and/or therapeutic targets in EAML patients.
Media coverage of disasters potentially damages mental health. Moreover, its effects may differ as recipients may have different emotional responses toward media. The present study examined whether social capital, known to be protective against mental problems, influences a recipient’s emotional response toward news media broadcasting of natural disasters via newspapers, television and internet in Japan. Three social capital components, social participation, social support and cognitive social capital, were considered in the present study as each component reportedly had different effect on mental health. This nationwide cross-sectional survey was undertaken in 2015 among 1,200 Japanese citizens aged 15 to 79 years who were selected using the multi-stage sampling procedure. Data were collected via the drop-off pick-up method using a printed structured questionnaire. Negative and positive emotions were classified based on recipients’ responses against news media. Among 1,190 participants who reported emotions toward news media, 30.9% (368) had experienced any natural disasters, 37.4% (445) belonged to at least one formal or informal organization (social participation), 40.2% (478) had high social support, and 68.8% (819) had high cognitive social capital. High social support was associated with both reduced negative emotional response (OR 0.66, 95% Confidence Interval (CI) 0.47-0.93) and increased positive emotional response (OR 1.48, 95% CI 1.04-2.12) in multivariate analyses, while high cognitive social capital was only associated with increased positive emotional response (OR 1.62, 95% CI 1.11-2.37). These results suggest protective effects of social support and cognitive social capital against news media coverage of natural disasters.
About 20% of patients with breast cancer are likely to develop breast cancer-related lymphedema (BCRL) following an axillary clearance, and BCRL can be refractory or irreversible to treatment. The aim of this pilot randomized controlled study was to evaluate the effectiveness of a 10-min holistic self-care program for patients with BCRL in Japan. The intervention group (n = 22) practiced the BCRL self-care program including 1) modified Japanese Radio Taiso (Rajio Taiso, national calisthenics in Japan), 2) gentle arm exercises combined with deep breathing, 3) central lymphatic drainage, and 4) skin care using a traditional lymphatic drainage technique daily for 6 months, while the control group (n = 21) received usual care from their hospitals. There was significant group*time interaction in the relative edema volume and relative volume change of the hand, with the intervention group having the better outcome. The intervention group showed significant improvement in transepidermal water loss as well as the mental health component summary score of the SF-8, most of BCRL-related symptoms, self-care time and score, frequencies of exercise, self-lymphatic drainage and skin care, and perceived adherence and effectiveness to self-care, although we were unable to exclude the possibility of the Hawthorne effect. Notably, even in the control group, the self-care was similarly increased, but the significant improvements were detected only in transepidermal water loss on the forearm and upper arm, pain and coldness. In conclusion, the patients who practiced the holistic BCRL self-care for 6 months have shown greater improvement.