B rain metastases occur in 10% to 40% of patients with cancer and are the most common central nervous system neoplasm in adults. 28,33 With increased surveillance, improved control of systemic cancer, and prolonged survival, the incidence of patients with brain metastases is increasing. 17 The management of brain metastases has been revolutionized in clinical oncology by 4 developments: improved brain imaging, improved management of systemic diseases, the distribution of stereotactic irradiation, and the extension of less invasive surgical techniques that enable brain metastases to be removed even from eloquent brain areas with minimal morbidity. 5Although stereotactic irradiation and pharmacotherapies contribute to the treatment outcome of patients with brain metastasis, resection is still a mainstay for large brain metastases.The indications for resection include a symptomatic mass, a mass with considerable edema requiring high-dose ABBREVIATIONS DS-GPA = diagnosis-specific graded prognostic assessment; KPS = Karnofsky Performance Status; NLR = neutrophil-to-lymphocyte ratio; OS = overall survival; RPA = recursive partitioning analysis. SUBMITTED OBJECTIVEThe median postoperative survival duration of patients with brain metastases who undergo tumor resection is 12 months. Most of these patients die of systemic metastases or the progression of primary cancer but not brain metastases. The criteria for indicating resection are still controversial. Systemic assessment is restricted, especially in patients who need emergent management for their large-size or life-threatening brain metastases. The neutrophil-tolymphocyte ratio (NLR) is reported to correlate with survival time or progression-free survival in patients with various cancers. However, NLR has not been assessed in patients with brain metastases. The impact of NLR on the survival data of patients who had undergone resection of brain metastases was retrospectively analyzed. METHODS The clinical records of patients who underwent resection of brain metastases at Shizuoka Cancer Center between May 2007 and January 2015 were retrospectively analyzed. NLR was calculated by using the data obtained from the latest examination before resection and before the administration of steroid therapy. Kaplan-Meier curves were used for the assessment of overall survival (OS). RESULTS Of the 105 patients included, 67 patients were male. The median age of the patients was 63 years (range 36-90 years). The primary cancers were lung, colon, breast, uterus, and other cancers in 48, 19, 10, 8, and 20 patients, respectively. The postresection median survival duration was 12 months (range 1-91 months) for the entire series. The optimum NLR threshold value was identified as 5. A significant difference in the median OS was found: 14 months for 82 patients with an NLR < 5 versus 5 months for 23 patients with an NLR ≥ 5 (p = 0.001). CONCLUSIONS In this study, an elevated preoperative NLR is a predictor of worse survival after resection for brain metastases. NLR is a simple, systemic m...

Diabetes causes skin complications, including xerosis and foot ulcers. Ulcers complicated by infections exacerbate skin conditions, and in severe cases, limb/toe amputations are required to prevent the development of sepsis. Here, we hypothesize that hyperglycemia induces skin barrier dysfunction with alterations of epidermal integrity. The effects of hyperglycemia on the epidermis were examined in streptozotocin-induced diabetic mice with/without insulin therapy. The results showed that dye leakages were prominent, and transepidermal water loss after tape stripping was exacerbated in diabetic mice. These data indicate that hyperglycemia impaired skin barrier functions. Additionally, the distribution of the protein associated with the tight junction structure, tight junction protein-1 (ZO-1), was characterized by diffuse and significantly wider expression in the diabetic mice compared to that in the control mice. In turn, epidermal cell number was significantly reduced and basal cells were irregularly aligned with ultrastructural alterations in diabetic mice. In contrast, the number of corneocytes, namely, denucleated and terminally differentiated keratinocytes significantly increased, while their sensitivity to mechanical stress was enhanced in the diabetic mice. We found that cell proliferation was significantly decreased, while apoptotic cells were comparable in the skin of diabetic mice, compared to those in the control mice. In the epidermis, Keratin 5 and keratin 14 expressions were reduced, while keratin 10 and loricrin were ectopically induced in diabetic mice. These data suggest that hyperglycemia altered keratinocyte proliferation/differentiation. Finally, these phenotypes observed in diabetic mice were mitigated by insulin treatment. Reduction in basal cell number and perturbation of the proliferation/differentiation process could be the underlying mechanisms for impaired skin barrier functions in diabetic mice.

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