Risk factors for unplanned reoperation after corrective surgery for adult spinal deformity.

To determine the major risk factors for unplanned reoperations (UROs) following corrective surgery for adult spinal deformity (ASD) and their interactions, using machine learning-based prediction algorithms and game theory. Patients who underwent surgery for ASD, with a minimum of two-year follow-up, were retrospectively reviewed. In total, 210 patients were included and randomly allocated into training (70% of the sample size) and test (the remaining 30%) sets to develop the machine learning algorithm. Risk factors were included in the analysis, along with clinical characteristics and parameters acquired through diagnostic radiology. Overall, 152 patients without and 58 with a history of surgical revision following surgery for ASD were observed; the mean age was 68.9 years (SD 8.7) and 66.9 years (SD 6.6), respectively. On implementing a random forest model, the classification of URO events resulted in a balanced accuracy of 86.8%. Among machine learning-extracted risk factors, URO, proximal junction failure (PJF), and postoperative distance from the posterosuperior corner of C7 and the vertical axis from the centroid of C2 (SVA) were significant upon Kaplan-Meier survival analysis. The major risk factors for URO following surgery for ASD, i.e. postoperative SVA and PJF, and their interactions were identified using a machine learning algorithm and game theory. Clinical benefits will depend on patient risk profiles.

Loss of myeloid-specific lamin A/C drives lung metastasis through Gfi-1 and C/EBPε-mediated granulocytic differentiation.

The immune-suppressive tumor microenvironment promotes metastatic spread and outgrowth. One of the major contributors is tumor-associated myeloid cells. However, the molecular mechanisms regulating their differentiation and function are not well understood. Here we report lamin A/C, a nuclear lamina protein associated with chromatin remodeling, was one of the critical regulators in cellular reprogramming of tumor-associated myeloid cells. Using myeloid-specific lamin A/C knockout mice and triple-negative breast cancer (TNBC) mouse models, we discovered that the loss of lamin A/C drives CD11b+ Ly6G+ granulocytic lineage differentiation, alters the production of inflammatory chemokines, decreases host antitumor immunity, and increases metastasis. The underlying mechanisms involve an increased H3K4me3 leading to the upregulation of transcription factors (TFs) Gfi-1 and C/EBPε. Decreased lamin A/C and increased Gfi-1 and C/EBPε were also found in the granulocytic subset in the peripheral blood of human cancer patients. Our data provide a mechanistic understanding of myeloid lineage differentiation and function in the immune-suppressive microenvironment in TNBC metastasis.

Sandwich technique using fibrin-coated collagen fleece for sellar reconstruction in large dural defects during transsphenoidal surgery.

PURPOSE: Various surgical methods to prevent intraoperative and postoperative cerebrospinal fluid (CSF) leaks during transsphenoidal approach (TSA) surgeries have been reported, but surgical techniques to address large dural defects have been less thoroughly investigated in the literature. The authors retrospectively evaluated the usefulness of the sandwich technique using fibrin-coated collagen fleece (TachoSil) to prevent intraoperative CSF leakage from large dural defects in TSA surgery. METHODS: In total, 101 cases of intraoperative CSF leaks were observed among 465 patients who underwent TSA surgery at a single university hospital between 2002 and 2014. Among them, cases with Grade 3 intraoperative CSF leakages and large diaphragmatic/dural defects were reconstructed via the sandwich technique using TachoSil or via the conventional technique using simple intrasellar packing with fat or synthetic materials, and these cases were enrolled in this study. RESULTS: A total of 28 cases with Grade 3 intraoperative CSF leakages were identified and analyzed. The sandwich technique using TachoSil was applied in 13 cases, and the conventional technique was applied in 15 cases. The postoperative CSF leakage was significantly decreased by the sandwich technique as compared to the conventional technique (retrospectively, 0 cases vs. 4 cases (30.8%); P=0.044). CONCLUSION: The sandwich technique using TachoSil can effectively prevent CSF leakage in cases with large dural defects during TSA surgery.

The Relationship between Waist Circumference and Work-related Injury in Reference to the Fourth Korea National Health and Nutrition Examination Survey.

OBJECTIVE: This study aims to investigate the relationship between waist circumference and work-related injury in reference to the fourth Korea National Health and Nutrition Examination Survey. METHODS: By analyzing data from the fourth Korea National Health and Nutrition Examination Survey conducted from 2007 to 2009, we estimated the rate of injury experience according to socioeconomic status, including occupational property, of 8,261 subjects. We performed logistic regression analysis with work-related injury experience rate as dependent variable and waist circumference as an independent variable, Odds ratios (OR) were calculated, which reflect the likelihood of work-related injury experience rate, and 95% confidence interval (95% CI) while controlling for relevant covariates with stratifying by sex, age, nature of injury, site of injury and occupational group. RESULTS: Among 797 persons who had injury experience over the past 1 year, 293 persons (36.8%) had work-related injury experience. After adjusting the confounding variables, the work-related injury was related to abnormal waist circumference (OR = 1.35; 95% CI: 1.02 ~ 1.78). In subgroups, ORs were higher in men (OR = 1.42; 95% CI: 1.02 ~ 1.98), professional, manager, and administrator (OR = 2.41; 95% CI: 1.10 ~ 5.28). Higher rate of injuries were noted in back and waist (OR = 2.92; 95% CI: 1.49 ~ 5.73), and transport accident had increased risk (OR = 1.60; 95% CI: 1.13 ~ 2.28). CONCLUSIONS: Work-related injury rate differed depending on the waist circumference. The abdominal obesity was associated with higher risk of work-related injury. This study would be useful in selecting appropriate priorities for work-related injury management in Korea.

Gemini vitamin D analog suppresses ErbB2-positive mammary tumor growth via inhibition of ErbB2/AKT/ERK signaling.

Numerous synthetic vitamin D analogs have been studied for their effects on the prevention and treatment of breast cancer. However, the inhibitory effects of naturally occurring 1alpha,25-dihydroxyvitamin D3 or its synthetic analogs on ErbB2 overexpressing mammary tumorigenesis have not been reported. Gemini vitamin D analogs are novel synthetic vitamin D derivatives with a unique structure of two six-carbon chains at C-20. We have previously shown that Gemini vitamin D analogs significantly inhibited carcinogen-induced estrogen receptor (ER)-positive mammary tumorigenesis and reduced ER-negative MCF10DCIS.com xenograft tumor growth without hypercalcemic toxicity. In the present study, we have determined the inhibitory effect of a potent Gemini vitamin D analog BXL0124 (1alpha,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-cholecalciferol) on the ErbB2/Her-2/neu overexpressing mammary tumorigenesis. The Gemini BXL0124 inhibits ErbB2-positive mammary tumor growth and down-regulates the phosphorylation of ErbB2, ERK and AKT in tumors of MMTV-ErbB2/neu transgenic mice. These effects of Gemini BXL0124 in vivo were confirmed by using the ErbB2 overexpressing tumor cells derived from the mammary tumors of MMTV-ErbB2/neu mice. In conclusion, the Gemini vitamin D analog BXL0124 inhibits the growth of ErbB2 overexpressing mammary tumors through regulating the ErbB2/AKT/ERK signaling pathways, suggesting that Gemini vitamin D analog may be considered for translational studies.

Mixed tocopherols prevent mammary tumorigenesis by inhibiting estrogen action and activating PPAR-gamma.

PURPOSE: Tocopherols are lipophilic antioxidants present in vegetable oils. Although the antioxidant and anticancer activities of alpha-tocopherol (vitamin E) have been studied for decades, recent intervention studies with alpha-tocopherol have been negative for protection from cancer in humans. The tocopherols consist of four isoforms, which are the alpha, beta, gamma, and delta variants, and recent attention is being given to other isoforms. In the present study, we investigated the inhibitory effect of a tocopherol mixture rich in gamma- and delta-tocopherols against mammary tumorigenesis. EXPERIMENTAL DESIGN: Female Sprague Dawley rats were treated with N-methyl-N-nitrosourea (NMU), and then fed diets containing 0.1%, 0.3%, or 0.5% mixed tocopherols rich in gamma- and delta-tocopherols for 9 weeks. Tumor burden and multiplicity were determined, and the levels of markers of inflammation, proliferation, and apoptosis were evaluated in the serum and in mammary tumors. The regulation of nuclear receptor signaling by tocopherols was studied in mammary tumors and in breast cancer cells. RESULTS: Dietary administration of 0.1%, 0.3%, or 0.5% mixed tocopherols suppressed mammary tumor growth by 38%, 50%, or 80%, respectively. Tumor multiplicity was also significantly reduced in all three mixed tocopherol groups. Mixed tocopherols increased the expression of p21, p27, caspase-3, and peroxisome proliferator activated receptor-gamma, and inhibited AKT and estrogen signaling in mammary tumors. Our mechanistic study found that gamma- and delta-tocopherols, but not alpha-tocopherol, activated peroxisome proliferator activated receptor-gamma and antagonized estrogen action in breast cancer. CONCLUSION: The results suggest that gamma- and delta-tocopherols may be effective agents for the prevention of breast cancer.