Delayed sternal closure does not reduce complications associated with coagulopathy and right ventricular failure after left ventricular assist device implantation

Delayed sternal closure (DSC) is occasionally adopted after implantation of left ventricular assist device (LVAD). Recent studies suggest that DSC be used for high risk group of patients with coagulopathy, hemodynamic instability or right ventricular failure. However, whether DSC is efficacious for bleeding complication or right ventricular failure is not known. This study is single center analysis of 52 patients, who underwent LVAD implantation. Of those 52 patients, 40 consecutive patients underwent DSC routinely. The sternum was left open with vacuum assist device after implantation of LVAD. Perioperative outcome of the patients who underwent routine DSC were compared with 12 patients who had immediate sternal closure (IC). Mean Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level of IC group and DSC group were 2.7 and 2.6, respectively. Postoperative bleeding (643 vs. 1469 ml, p?<?0.001), duration of inotropic support (109 vs. 172 h, p?=?0.034), and time to extubation (26 vs. 52 h, p?=?0.005) were significantly increased in DSC group. Length of ICU stay (14 vs. 15 days, p?=?0.234) and hospital stay (28 vs. 20 days, p?=?0.145) were similar. Incidence of right ventricular failure and tamponade were similar in the two groups. Routine DSC after implantation of an LVAD did not prove to be beneficial in reducing complications associated with coagulopathy and hemodynamic instability including cardiac tamponade or right ventricular failure. We suggest that DSC be selectively applied for patients undergoing LVAD implant.     

Use of 18F-sodium fluoride bone PET for disability evaluation in ankle trauma: a pilot study

Obesity and high radiologic breast density independently increase breast cancer risk. We evaluated the effect of surgical weight loss on mammographic density (MD). Patients undergoing bariatric surgery and screening mammography (MG) were identified, data regarding demographics, comorbidities, calculated and genetic breast cancer risk was collected. Patients had a MG before and after surgery. Fellowship-trained breast radiologists assigned Breast Imaging Reporting and Data System density categories. Patients underwent sleeve gastrectomy (n = 56) or gastric bypass (n = 7), 78% had hypertension, 48% had diabetes. Four had deleterious BRCA mutations, four were calculated high risk. Mean weight loss = 28.7 kg. Mean initial BMI = 44.3 kg/m2 (range:33–77), final BMI = 33.6 kg/m2 (range:20–62;p < 0.01). Density was unchanged in 53, decreased in 1, increased in 9. Of these 9(14%), 5 changed from almost entirely fatty to scattered MD, and 4 changed from scattered MD to heterogeneously dense. Mean weight loss of the 9 with increased MD was greater than the cohort (37.7vs.28.7 kg;p < 0.01). Surgical weight loss increased MD in 14%. Increased MD masks malignancies, patients may benefit from additional screening based on calculated risk assessments that include MD.     

Stable paclitaxel formulations in oily contrast medium.

Stable paclitaxel/Lipiodol solutions as well as emulsions were developed for the treatment of solid tumors including hepatocellular carcinoma. Paclitaxel could be dissolved in Lipiodol, an oily contrast medium, but precipitated out and formed aggregates with time. Paclitaxel precipitation was due to the inter- and intra-molecular hydrogen bonding of paclitaxel molecules. Time-dependent paclitaxel aggregation was completely prevented by adding small amounts of additional solvents, which are miscible with Lipiodol. It was also notable that paclitaxel helped in stabilizing the water-in-oil (w/o) type emulsion of Lipiodol and Iopamiro. The stability, physical properties and in vitro drug release profiles of the stable paclitaxel solutions and emulsions were characterized. When the stable oily paclitaxel solution was used for the treatment of B16F10 melanoma in C57BL/6 mice, the malignant cells were eradicated completely in 2 weeks, whereas the solid tumor grew rapidly and metastasized to the thigh and to other organs in the control group. Also, the mice survived for more than 1 year after the paclitaxel treatment, whereas all of those in the control group died in 40 days.     

3,3'-Diindolylmethane induces immunotoxicity via splenocyte apoptosis in neonatal mice

3,3′-Diindolylmethane (DIM), a major product of indole-3-carbinol derived from vegetables of the genus Brassica, exhibits chemotherapeutic activity and various immune modulatory effects in animal models and in vitro studies. Although extensive studies have only focused on DIM's beneficial effects, the toxic effects of DIM on the immune systems have not been clearly elucidated. The aim of this study was to explore the immunotoxic effects of DIM in a neonatal mouse and to further evaluate whether DIM administration affects rotavirus (RV)-induced gastroenteritis. Interestingly, multiple immunotoxic effects were observed in the DIM treated group, including decreases in various immune cells (F4/80⁺, CD11c⁺, CD19⁺, and CD3⁺ cells) in the spleen, induction of splenic white pulp atrophy, an increase in immune cell apoptosis, and decreased expression of various toll-like receptors (TLRs) in the spleen and small intestine. Apoptosis was notably promoted by up-regulating caspase-3 activity and by the change in the ratio of Bcl-2/Bax activities. Finally, oral administration of DIM led to deterioration of RV-induced intestinal disease and delayed viral clearance in the intestine and MLNs. Our results indicate that oral administration of DIM in neonatal mice induces immunotoxicity and hampers efficient RV clearance in the intestine. This new information about the immunotoxic roles of DIM in a newborn mouse model may provide valuable clues for the development of a safe supplement, especially one designed for human infants.     

Rapid identification of thrombocytopenia-associated multiple organ failure using red blood cell parameters and a volume/hemoglobin concentration cytogram

Thrombocytopenia-associated multiple organ failure (TAMOF) has a high mortality rate when not treated, and early detection of TAMOF is very important diagnostically and therapeutically. We describe herein our experience of early detection of TAMOF, using an automated hematology analyzer. From 498,390 inpatients, we selected 12 patients suspected of having peripheral schistocytosis, based on the results of red blood cell (RBC) parameters and a volume/hemoglobin concentration (V/HC) cytogram. We promptly evaluated whether the individual patients had clinical manifestations and laboratory findings were consistent with TAMOF. Plasma exchanges were then performed for each patient. All 12 patients had TAMOF. The mean values of RBC parameters were significantly higher in all of the patients than with the reference range, however, 3 patients had % RBC fragments within the reference range. The mean value of ADAMTS-13 activity was slightly lower in patients compared with the reference range. Of the 12 patients, remission was obtained in 9 patients (75%) within 4 to 5 weeks using plasma exchanges. Three patients died. An increased percentage of microcytic hyperchromic cells with anisocytosis and anisochromia indicated the presence of schistocytes, making it an excellent screening marker for TAMOF. Identification of TAMOF with RBC parameters and a V/HC cytogram is a facile and rapid method along with an automated hematology analyzer already in use for routine complete blood cell counting test.     

Association of polycystic ovarian syndrome with human leukocyte antigen polymorphism in Korean women

Although several studies have demonstrated the genetic contribution to polycystic ovarian syndrome (PCOS), the cause of this syndrome remains unclear. The aim of this study was to elucidate the relationship between human leukocyte antigen (HLA) systems and PCOS in Koreans. We compared the HLA-A, B and DRB1 genotype distribution of 52 PCOS patients and 67 healthy Korean women. In addition, we investigated the association of HLA with free-testosterone level. HLA-A*11, A*31 and B*54 showed increased phenotype frequencies (PFs) in PCOS women compared to controls (p = 0.032, OR 2.79; p = 0.019, OR 6.05; p = 0.002, OR 6.40). HLA-DRB1*15 showed negative correlations with the free-testosterone concentration both in total subjects and PCOS patients (p = 0.024 and p = 0.008). The results of the study suggest mild associations of HLA alleles with pathophysiology of PCOS and/or testosterone production in PCOS. Further investigation in a large number of subjects, including subdivision and multi-population studies, will need to be conducted to prove the consistent or variable association in PCOS.     

Synthesis and nuclear factor-κB inhibitory activities of 6- or 7-methylchroman-2-carboxylic acid N-(substituted) phenylamides

A series of 6- or 7-methylchroman-2-carboxylic acid N-(substituted) phenylamides (2a-s, 3a-s) were synthesized. Their abilities to inhibit nuclear factor-κB (NF-κB) activity were evaluated in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. Compounds with substituents such as -H, -CH₃, and -CF₃ on the phenyl ring were poor inhibitors of NF-κB. The most active NF-κB inhibitors contained 4-Cl (3s) and 4-OMe (3g) in the 7-methylchroman-2-carboxamide derivatives and 2-OH (2b) and 4-Cl (2s) in the 6-methylchroman-2-carboxamide derivatives (IC₅₀: 20.2–24.0 μM). These were slightly more potent than a reference compound, KL-1156 (1) (IC₅₀: 43.9 μM).