A pilot study of autologous CD34-depleted bone marrow mononuclear cell transplantation via the hepatic artery in five patients with liver failure

Background aimsMany rodent experiments and human studies on stem cell therapy have shown promising therapeutic approaches to liver diseases. We investigated the clinical outcomes of five patients with liver failure of various causes who received autologous CD34-depleted bone marrow-derived mononuclear cell (BM-MNC) transplantation, including mesenchymal stromal cells, through the hepatic artery.MethodsCD34-depleted BM-MNCs were obtained from five patients waiting for liver transplantation by bone marrow aspiration and using the CliniMACS CD34 Reagent System (Miltenyi Biotech, Bergisch Gladbach, Germany), and autologous hepatic artery infusion was performed. The causes of hepatic decompensation were hepatitis B virus (HBV), hepatitis C virus (HCV), propylthiouracil-induced toxic hepatitis and Wilson disease.ResultsSerum albumin levels improved 1 week after transplantation from 2.8 g/dL, 2.4 g/dL, 2.7 g/dL and 1.9 g/dL to 3.3 g/dL, 3.1 g/dL, 2.8 g/dL and 2.6 g/dL. Transient liver elastography data showed some change from 65 kPa, 33 kPa, 34.8 kPa and undetectable to 46.4 kPa, 19.8 kPa, 29.1 kPa and 67.8 kPa at 4 weeks after transplantation in a patient with Wilson disease, a patient with HCV, and two patients with HBV. Ascites decreased in two patients. One of the patients with HBV underwent liver transplantation 4 months after the infusion, and the hepatic progenitor markers (cytokeratin [CD]-7, CD-8, CD-9, CD-18, CD-19, c-Kit and epithelial cell adhesion molecule [EpCAM]) were highly expressed in the explanted liver.ConclusionsSerum albumin levels, liver stiffness, liver volume, subjective healthiness and quality of life improved in the study patients. Although these findings were observed in a small population, the results may suggest a promising future for autologous CD34-depleted BM-MNC transplantation as a bridge to liver transplantation in patients with liver failure.     

Lead Accumulation as Possible Risk Factor for Primary Open-Angle Glaucoma

The objective of this study was to investigate the relationship between preeclampsia and iodine levels and magnesium concentration in the blood of subjects in the northeast Anatolia region where iodine deficiency is common. Blood specimens were obtained from 24 preeclamptic and 16 healthy pregnant women. Iodine levels in blood were determined by the Foss method based on the Sandell–Kolthoff reaction. Serum protein-bound iodine (PBI) levels and magnesium concentration in maternal blood were lower in patients with severe preeclampsia compared to normal pregnant women (8.46?±?1.22 vs. 11.46?±?1.71 μg/dL, p?<?0.001, 1.63?±?0.05 vs. 1.86?±?0.05 mg/dL, p?<?0.001, respectively). Serum PBI levels and magnesium concentration in umbilical cord blood were higher in patients with severe preeclampsia than in normal pregnant women (8.84?±?1.9 vs. 7.33?±?1.07 μg/dL, p?<?0.05, 2.48?±?0.03 vs. 2.02?±?0.01 mg/dL, p?<?0.001, respectively). There was a positive correlation between the serum PBI levels in maternal blood and magnesium concentration in maternal blood in patients with severe preeclampsia (r?=?0.41, p?<?0.05). Thus, iodine may be one factor contributing to the pathophysiology of preeclampsia. Iodine supplementation may be effective therapy in preeclamptic in pregnant women.     

Iron Deficiency Without Anemia Is Associated with Anger and Fatigue in Young Japanese Women

Iron deficiency without anemia (IDNA), the most prevalent nutritional deficiency worldwide, affects young women of reproductive age. This study aimed to elucidate the relationship between IDNA and mental and somatic symptoms including anger and fatigue using the Japanese version of the Cornell Medical Index Health Questionnaire (CMI–J). Data regarding demographic characteristics, anthropometry, hematological, and biochemical indices of the iron status, frequencies of selected food intakes assessed by self-administered food frequency questionnaires (FFQs), frequencies of nonspecific symptoms, and grades of neurotic tendencies assessed by CMI–J were collected from 76 young women aged 18–22 years living in the metropolitan area of Tokyo, Japan. The subjects were classified as having IDNA (hemoglobin (Hb)?≥?12 g/dL and serum ferritin?<?20 ng/mL; n?=?29), having iron deficiency anemia (IDA) (Hb?<?12 g/dL and serum ferritin?<?20 ng/mL; n?=?10), or having a normal iron status (Hb?≥?12 g/dL and serum ferritin?≥?20 ng/mL; n?=?36). One subject was excluded from the analyses because of Hb?<?12 g/dL and serum ferritin?≥?20 ng/mL. Fisher’s protected least significant difference and the Dwass–Steel–Chritchlow–Fligner multiple comparison tests were used to compare the data of the three groups. P values <0.05 were considered significant. Sections M–R (mental complaints) were significantly higher in the IDNA subjects than in the normal subjects. No significant difference in CMI scores was found between the normal and IDA subjects. Sections I (fatigability), Q (anger), and R (tension) were significantly higher in the IDNA subjects than in the normal subjects, regardless of no significant differences between the normal and IDA subjects in those sections. Young women with IDNA demonstrated a significantly higher proportion of neurotic tendencies (grades II–IV). The intake frequency score of canned or bottled green tea fortified with vitamin C was significantly higher in the IDNA subjects than the IDA subjects. The findings suggest that IDNA may be a risk factor for anger, fatigue, and tension in women of childbearing age.     

Hair Selenium Levels in Hepatic Steatosis Patients

The purpose of this study was to assess hair selenium levels of liver patients suffering from hepatic simple steatosis and non-alcoholic steatohepatitis (NASH) in central areas of China. Selenium was measured by an atomic absorption spectrophotometer equipped with the hydride generation system. The levels of selenium in healthy individuals ranged between 0.3 and 0.9 μg/g, and mean hair selenium levels in the male population and female population were 0.59?±?0.18 and 0.57?±?0.15 μg/g, respectively. These concentrations did not vary significantly (P?>?0.05) in relation to the gender. One hundred-eighteen individuals of both sexes aged between 15 and 60 years with hepatic simple steatosis and NASH were selected for this study. The mean and standard deviation of hair selenium concentrations observed in male and female patients with hepatic simple steatosis were 0.54?±?0.16 and 0.50?±?0.15 μg/g, respectively, while the mean and standard deviation of hair selenium concentrations observed in male and female patients with NASH were 0.40?±?0.14 and 0.41?±?0.12 μg/g. Analysis of t test showed a significant difference between NASH (P?<?0.001) patients in hair selenium concentrations when compared with controls.     

Activation of the EIF2α/ATF4 and ATF6 Pathways in DU-145 Cells by Boric Acid at the Concentration Reported in Men at the US Mean Boron Intake

We aimed to evaluate the association of exposure to lead with glycated hemoglobin (HbA1c), fasting glucose levels (FGLs), and the likelihood for dysglycemia. We accessed data from Canada Health and Measures Survey. General linear models were used to estimate the association between blood lead concentrations (BPb) and both HbA1c and FGLs, while controlling for confounders. Multivariate logistic regression was used for assessing the relation between BPb and the likelihood for dysglycemia. FGLs in participants with moderate BPb (2.5–5.0 μg/dL) were 1.03 (95 % CI 1.00–1.06) times higher compared with participants with BPb < 2.5 μg/dL. Equivalent figures for those with BPb ≥ 5.0 μg/dL were 1.10 (95 % CI 1.01–1.20) times, relative to the lowest stratum. This association was attenuated using HbA1c to define dysglycemia. Lead exposure was associated with the likelihood for neither FGLs ≥ 1.10 g/L nor HbA1c ≥ 5.7 %. The association between lead exposure and dysglycemia, if any, is likely to be very modest, at least at the population level.     

The Association Between Effective Dose of Magnesium and Mild Compulsive Exercise on Spatial Learning,Memory, and Motor Activity of Adult Male Rats

The relationship of minerals and trace elements with inflammatory bowel disease (IBD) is complex. Alterations in their metabolism can be induced by the diseases and their complications. To study the role of trace elements in IBD patients’ serum zinc and copper and their related enzymes, including superoxide dismutase (SOD), activity were measured in patients with IBD patients as well as in healthy subjects. In addition, the correlation between serum trace element levels, albumin, total protein, urea level, copper/zinc ratio, and disease activity (DA) was determined in these subjects. Serum samples were obtained from 35 patients (19 ulcerative colitis (UC) and 16 Crohn’s disease (CD)) in the active phase of the disease and 30 healthy control subjects. Serum levels of zinc, copper, SOD activity, albumin, total protein, and urea were measured. The results were compared between the two groups using independent Student’s t test in statistical analysis. Serum levels of zinc, SOD activity, albumin, and total protein were significantly lower (P < 0.05) in patients than controls, while serum urea level was significantly higher in patients compared to controls. Copper concentrations did not differ between patients with IBD (mean ± SD, 58.8 ± 20.7 μg/d) and controls (55.57 ± 12.6 μg/d). Decreased levels of zinc and SOD activity are associated with increased inflammatory processes indicating inappropriate antioxidant system in patients with IBD. Additionally, lower levels of albumin and total protein with higher level of urea reflect metabolic problems in liver system.     

Elevated Fructosamine Levelsin Acquired Immunodeficiency Syndrome

ObjectiveTo investigate whether the mechanism of increased glycation in acquired immunodeficiency syndrome (AIDS) is due to an alteration in a circulatory plasma enhancer.MethodsWe assessed glycation of serum protein and hemoglobin in patients with AIDS without altered carbohydrate metabolism. Fasting concentrations of glucose, ethanol, vitamin E, fructosamine, hemoglobin, hemoglobin A1c (A1C), and partial pressure of alveolar oxygen (Pao₂) were determined in 50 men with AIDS and in 25 age-matched healthy men in whom normal glucose tolerance was established by oral glucose tolerance tests.ResultsFasting serum glucose was not significantly different between the men with AIDS (87 ± 4 mg/dL) and the healthy male volunteers (84 ± 6 mg/dL); however, A1C (6.9 ± 0.2%) and serum fructosamine levels (288 ± 15 μmol/L) were significantly higher (P < .01) in the patients with AIDS than in the normal subjects (A1C, 5.6 ± 0.1%; fructosamine, 204 ± 14 μmol/L). Moreover, both A1C and fructosamine concentrations were significantly higher (P < .01) in the patients with AIDS than in the normal subjects divided into subgroups on the basis of fasting plasma glucose concentrations (70 to 79 mg/dL, 80 to 89 mg/dL, and 90 to 99 mg/dL). None of the study participants had anemia (hemoglobin < 12 g/dL) or hypoxia (Pao₂ < 95 mm Hg), and serum ethanol was undetectable. Furthermore, vitamin E concentrations were not significantly different between the patients with AIDS (25 ± 3 mg/L) and the normal subjects (22 ± 4 mg/L).ConclusionOn the basis of this study, glycation of some circulating proteins appears to be enhanced in AIDS and may be induced by an undetermined plasma enhancer, inasmuch as known circulating factors promoting glycation were absent. (Endocr Pract. 2008;14:686-690)     

Anemia in Patients With Diabetes and Prediabetes With Normal Kidney Function: Prevalence and Clinical Outcomes

ObjectiveAnemia is a known complication of diabetes mellitus (DM); however, its prevalence and prognostic relevance in patients with DM and pre-DM with normal kidney function have not been well defined. This study assessed the prevalence of anemia in patients with DM and pre-DM and evaluated its association with clinical outcomes during a 4-year follow-up period.MethodsThis retrospective analysis included patients with DM and pre-DM referred to the Meir Medical Center Endocrine Institute in 2015. Patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min or any other recognized cause of anemia were excluded. The risk of developing microvascular or macrovascular complications or of death during the 4-year follow-up period was determined.ResultsA total of 622 patients (408 with DM and 214 with pre-DM) were included. The mean age of the patients was 64 ± 10.6 years, and 70% were women. The baseline hemoglobin A1C level was 7.1% ± 1.7% (54 mmol/mol), and the eGFR was 86.1 ± 15.3 mL/min. At the time of inclusion, 77 patients (19%) with DM and 23 (11%) with pre-DM had anemia (hemoglobin level 11.9 ± 0.8 and 11.8 ± 0.8 g/dL, respectively), compared with normal hemoglobin levels of 13.8 ± 0.9 and 13.7± 0.9 g/dL, respectively, in the others. A multivariable analysis demonstrated an inverse correlation between baseline hemoglobin (as a continuous variable) and mortality (P = .035), microvascular complications (P = .003), and eGFR decline (P < .001) but not between baseline hemoglobin and macrovascular complications (P = .567).ConclusionThis study found a significant prevalence of anemia unrelated to renal failure, both in patients with DM and pre-DM. Anemia in these patients is associated with the development of microvascular complications, eGFR decline, and mortality. These results underscore the need for intensive lifestyle and pharmacologic interventions in these patients.     

Efficacy of Various Combined Blood Purification Techniques for Treating Patients with Non-viral Acute Liver Failure

We sought to study the clinical efficacy of various combined blood purification techniques in patients with non-viral acute liver failure complicated by multiple organ dysfunction syndrome (MODS). For this purpose, 19 patients diagnosed of mid- or late-stage liver failure with MODS score-4 were randomly divided into 3 treatment groups of PE+HP+CVVHDF, PE+CVVHDF, and HP+CVVHDF, respectively. Pre- and post-treatment heart rate (HR), mean arterial pressure (MAP), arterial blood gases (pH, PaO₂, and PaCO₂), hepatic function, platelet count, and blood coagulation were determined. The data show significant improvement in HR, MAP, PaO₂/FiO₂, total bilirubin (TBIL), and alanine aminotransferase (ALT) levels after treatment (P < 0.05). TBIL decreased more significantly after treatment in PE+CVVHDF and PE+HP+CVVHDF groups (P < 0.01). Significant improvement in prothrombin time and albumin was observed only in PE+CVVHDF and PE+HP+CVVHDF groups (P < 0.05). The decrease of TBIL and improvement of PaO₂/FiO₂ ratio were more pronounced in PE+HP+CVVHDF than in HP+CVVHDF group (P < 0.05). To conclude, liver function was relatively improved by all the three combined blood purification techniques used; however, PE+HP+CVVHDF approach was found more efficient in the removal of toxic metabolites, especially bilirubin. The data suggest that the combined blood purification techniques used were effective and involved minor side effects.     

Preoperative oral supplementation with carbohydrate and branched-chain amino acid-enriched nutrient improves insulin resistance in patients undergoing a hepatectomy: a randomized clinical trial using an artificial pancreas

Glucose metabolism is adversely affected in patients following major surgery. Patients may develop hyperglycemia due to a combination of surgical stress and postoperative insulin resistance. A randomized trial was conducted to elucidate the effect of preoperative supplementation with carbohydrates and branched-chain amino acids on postoperative insulin resistance in patients undergoing hepatic resection. A total of 26 patients undergoing a hepatectomy for the treatment of a hepatic neoplasm were randomly assigned to receive a preoperative supplement of carbohydrate and branched-chain amino acid-enriched nutrient mixture or not. The postoperative blood glucose level and the total insulin requirement for normoglycemic control during the 16 h following hepatic resection were determined using the artificial pancreas STG-22. Postoperative insulin requirements for normoglycemic control in the group with preoperative nutritional support was significantly lower than that in the control group (P = 0.039). There was no incidence of hypoglycemia (<40 mg/dL) observed in patients, including those with diabetes mellitus, when the STG-22 was used to control blood glucose levels. STG-22 is a safe and reliable tool to control postoperative glucose metabolism and evaluate insulin resistance. The preoperative oral administration of carbohydrate and branched-chain amino acid-enriched nutrient is of clinical benefit and reduces postoperative insulin resistance in patients undergoing hepatic resection.     

Inhibitory effect of tumor necrosis factor α on gluconeogenesis in perfused rat liver

Tumor necrosis factor α (TNFα) is a cytokine involved in many metabolic responses in both normal and pathological states. Considering that the effects of TNFα on hepatic gluconeogenesis are inconclusive, we investigated the influence of this cytokine in gluconeogenesis from various glucose precursors. TNFα (10 μg/kg) was intravenously injected in rats; 6 h later, gluconeogenesis from alanine, lactate, glutamine, glycerol, and several related metabolic parameters were evaluated in situ perfused liver. TNFα reduced the hepatic glucose production (p < 0.001), increased the pyruvate production (p < 0.01), and had no effect on the lactate and urea production from alanine. TNFα also reduced the glucose production (p < 0.01), but had no effect on the pyruvate production from lactate. In addition, TNFα did not alter the hepatic glucose production from glutamine nor from glycerol. It can be concluded that the TNFα inhibited hepatic gluconeogenesis from alanine and lactate, which enter in gluconeogenic pathway before the pyruvate carboxylase step, but not from glutamine and glycerol, which enter in this pathway after the pyruvate carboxylase step, suggesting an important role of this metabolic step in the changes mediated by TNFα.     

The Roles of Albumin Levels in Head and Neck Cancer Patients with Liver Cirrhosis Undergoing Tumor Ablation and Microsurgical Free Tissue Transfer

Objective

To evaluate the changes of serum albumin levels during the peri-operative period, and correlate these changes to surgical outcomes, postoperative morbidity and mortality in head and neck cancer patients with cirrhosis.

Methods

57 patients with liver cirrhosis out of 3,022 patients who underwent immediate free flap reconstruction after surgical ablation of head and neck cancer performed over a 9-year period were included in the study. Two sets of groups were arranged based on the preoperative albumin (>3.5 g/dL vs. ≤ 3.5 g/dL) and POD1 albumin (>2.7 g/dL vs. ≤ 2.7 g/dL) levels and were compared with respect to patient-related variables, surgical outcomes, medical and surgical complications, and mortalities.

Results

All patients had significant decreases in albumin levels postoperatively. Hypoalbuminemia, both preoperative and postoperative, was associated with the model for end-stage liver disease (MELD) score, the amount of blood loss, the duration of ICU stay and hospital stay, and postoperative medical and surgical complications. In particular, preoperative hypoalbuminemia (serum albumin ≤ 3.5 g/dL) was associated strongly with medical complications and mortality, while postoperative hypoalbuminemia (serum albumin ≤ 2.7 g/dL) with surgical complications.

Conclusion

Our study demonstrated the prognostic values of albumin levels in head and neck cancer patient with liver cirrhosis. The perioperative albumin levels can be utilized for risk stratification to potentially improve surgical and postoperative management of these challenging patients.     

Protective effects of vitamins (C and E) and melatonin co-administration on hematological and hepatic functions and oxidative stress in alloxan-induced diabetic rats

The present study aimed to investigate the potential effects of vitamins (C and E)/melatonin co-administration on the hematologic and hepatic functions and oxidative stress in alloxan-induced diabetic rats. The intraperitoneal injection of alloxan (120 mg/kg b.w. for 2 days) induced a significant increase of blood glucose levels (hyperglycemia) associated with serious hematologic disorders (P?<?0.01) evidenced by the decrease in the levels of red blood cell count (RBC) (?18 %), hematocrit (Ht) (?18 %), hemoglobin content (Hb) (?36 %), mean corpuscular hemoglobin (MCH) (?17 %), and mean corpuscular hemoglobin concentration (MCHC) (?16 %). The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and the plasmatic levels of total cholesterol and triglyceride contents of diabetic rats were, however, noted to undergo significant increases by 42 % (P?<?0.01), 134 % (P?<?0.001), 27.5 % (P?<?0.01), 147 % (P?<?0.001), and 67 % (P?<?0.01), respectively, as compared to the control animals. Furthermore, a significant increase in malondialdehyde (MDA) content and a significant decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were observed in the plasma and hepatic tissues of diabetic rats when compared to the controls. Interestingly, the treatment with vitamins (C, E) in combination with melatonin was noted to reduce the plasma levels of glucose, lower the MDA levels, and restore the hematologic parameters and biochemical and antioxidant levels of diabetic rats back to normal values, alleviating diabetes metabolic disorders in rats.     

Investigation of in vitro and in vivo antioxidant potential of secoisolariciresinol diglucoside

The present study was designed to evaluate the in vitro and in vivo ameliorative antioxidant potential of secoisolariciresinol diglucoside (SDG). In vitro antioxidant activity of synthetic SDG was carried out using DPPH, reducing power potency, and DNA protection assays. Wistar albino rats weighing 180–220 g were used for in vivo studies and liver damage was induced in the experimental animals by a single intraperitoneal (I.P.) injection of CCl₄ (2 g/kg b.w.). Intoxicated animals were treated orally with synthetic SDG at (12.5 and 25 mg/kg b.w.) and Silymarin (25 mg/kg) for 14 consecutive days. The levels of catalase (CAT), superoxide dismutase (SOD), peroxidase (POX), and lipid peroxidase (LPO) were measured in liver and kidney homogenates. The synthetic SDG exerts high in vitro antioxidant potency as it could scavenge DPPH at a IC₅₀ value of 78.9 μg/ml and has dose-dependent reducing power potency and protected DNA at 0.5 mg/ml concentration. Oral administration of synthetic SDG at 12.5 and 25 mg/kg b.w. showed significant protection compared to Silymarin (25 mg/kg) and the activities of CAT, SOD, and POX were markedly increased (P < 0.05), whereas LPO significantly decreased (P < 0.001) in a dose-dependent manner in liver and kidney in both pre- and post-treatment groups when compared to toxin-treated group. The results of in vitro and in vivo investigations revealed that synthetic SDG at 25 mg/kg b.w. is associated with beneficial changes in hepatic enzyme activities and thereby plays a key role in the prevention of oxidative damage in immunologic system.     

Association of Serum Levels of Iron,Copper, and Zinc,and Inflammatory Markers with Bacteriological Sputum Conversion During Tuberculosis Treatment

Iron, copper, and zinc are key micronutrients that play an important role in the immune response to Mycobacterium tuberculosis. The present study aimed to evaluate the association between serum levels of those micronutrients, inflammatory markers, and the smear and culture conversion of M. tuberculosis during 60 days of tuberculosis treatment. Seventy-five male patients with pulmonary tuberculosis (mean age, 40.0?±?10.7 years) were evaluated at baseline and again at 30 and 60 days of tuberculosis treatment. Serum levels of iron, copper, zinc, albumin, globulin, C-reactive protein, and hemoglobin, and smear and cultures for M. tuberculosis in sputum samples were analyzed. Compared to healthy subjects, at baseline, patients with PTB had lower serum iron levels, higher copper levels and copper/zinc ratio, and similar zinc levels. During the tuberculosis treatment, no significant changes in the serum levels of iron, zinc, and copper/zinc were observed. Lower serum copper levels were associated with bacteriological conversion in tuberculosis treatment (tuberculosis-negative) at 30 days but not at 60 days (tuberculosis-positive). C-reactive protein levels and the C-reactive protein/albumin ratio were lower in tuberculosis-negative patients than in tuberculosis-positive patients at 30 and 60 days after treatment. Albumin and hemoglobin levels and the albumin/globulin ratio in patients with pulmonary tuberculosis increased during the study period, regardless of the bacteriological results. High serum globulin levels did not change among pulmonary tuberculosis patients during the study. Serum copper levels and the C-reactive protein/albumin ratio may be important parameters to evaluate the persistence of non-conversion after 60 days of tuberculosis treatment, and they may serve as predictors for relapse after successful treatment.     

Upregulation of microRNA-375 is associated with poor prognosis in pediatric acute myeloid leukemia

A genome-wide serum miRNA expression analysis previously showed the upregulation of microRNA-375 (miR-375) in acute myeloid leukemia (AML) patients compared with healthy controls. The aim of this study was to investigate the expression patterns and the prognostic relevance of miR-375 in pediatric AML. Expression levels of miR-375 in bone marrow mononuclear cells were detected by real-time quantitative PCR in a cohort of 106 patients with newly diagnosed pediatric AML. Expression levels of miR-375 in the bone marrow of pediatric AML patients were significantly higher than those in normal controls (P < 0.001). Then, miR-375 upregulation occurred more frequently in French–American–British classification subtype M7 than in other subtypes (P < 0.001). Regarding to cytogenetic risk, the expression levels of miR-375 in pediatric AML patients with unfavorable karyotypes were dramatically higher than those in intermediate and favorable groups (P = 0.002). Moreover, high miR-375 expression was significantly associated with shorter relapse-free survival (P < 0.001) and overall survival (P < 0.001) in pediatric AML patients. Multivariate analysis further identified miR-375 expression and cytogenetics risk as independent prognostic factors for both relapse-free survival and overall survival. In particular, the prognostic relevance of miR-375 expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics. Our findings suggest for the first time that the upregulation of miR-375 may be one of the molecular mechanisms involved in the development and progression of pediatric AML. Since its correlation with poor relapse-free survival and overall survival, miR-375 may be a novel biomarker to improve the management of pediatric AML patients.     

Use of yeast (<Emphasis Type="Italic">Pichia kudriavzevii</Emphasis>) as a novel feed additive to ameliorate the effects of aflatoxin B<Subscript>1</Subscript> on broiler chicken performance

The aim of this study was to evaluate the efficacy of autochthonous Pichia kudriavzevii as a novel bioadsorbent for aflatoxin B₁ (AFB₁). The selection of this yeast was based on the AFB₁ adsorption capacity previously demonstrated in vitro (Magnoli et al. 2016). One-day-old Cobb broilers (n = 160) were randomly assigned to four dietary treatments (T1: basal diet (B); T2: B + 0.1% yeast; T3: B + AFB₁, 100 μg/kg; T4: B + 0.1% yeast + AFB₁, 100 μg/kg). Performance parameters (average daily weight gain body, average daily consumption, feed conversion ratio, carcass weight, and dead weight), biochemical parameters (albumin, globulin, and albumin/globulin), liver pathological changes, and AFB₁ residual levels in the liver and excreta were evaluated. Significant differences (P < 0.05) in performance parameters were observed among treatments and controls: T3 group showed the lowest average daily body weight gain value while in T4 group, the value of this parameter increased significantly (P < 0.05). T3 and T4 groups showed the lowest and highest values for average daily feed consumption, respectively. The feed conversion ratio (FC) showed no significant differences among treatments. T3 group showed the lowest dead weight and carcass weight compared with T1 group. The biochemical parameters showed no significant differences among treatments. T3 group showed macroscopic and microscopic liver changes compared to the control. Aflatoxin B₁ levels (μg/g) were detected in broiler livers and showed significant differences among treatments (P < 0.05). In conclusion, native P. kudriavzevii incorporation (0.1%) in broiler diets containing AFB₁ was shown to be effective in ameliorating the adverse effects of AFB₁ on production.     

Daily Inpatient Glycemic Survey (DINGS): A Process to Remotely Identify and Assist in the Management of Hospitalized Patients with Diabetes and Hyperglycemia

Objective: Hyperglycemia, hypoglycemia, and glycemic variability have been associated with increased morbidity, mortality, and overall costs of care in hospitalized patients. At the Stratton VA Medical Center in Albany, New York, a process aimed to improve inpatient glycemic control by remotely assisting primary care teams in the management of hyperglycemia and diabetes was designed.Methods: An electronic query comprised of hospitalized patients with glucose values <70 mg/dL or >350 mg/dL is generated daily. Electronic medical records (EMRs) are individually reviewed by diabetes specialist providers, and management recommendations are sent to primary care teams when applicable. Glucose data was retrospectively examined before and after the establishment of the daily inpatient glycemic survey (DINGS) process, and rates of hyperglycemia and hypoglycemia were compared.Results: Patient-day mean glucose slightly but significantly decreased from 177.6 ± 64.4 to 173.2 ± 59.4 mg/dL (P<.001). The percentage of patient-days with any value >350 mg/dL also decreased from 9.69 to 7.36% (P<.001), while the percentage of patient-days with mean glucose values in the range of 90 to 180 mg/dL increased from 58.1 to 61.4% (P<.001). Glycemic variability, assessed by the SD of glucose, significantly decreased from 53.9 to 49.8 mg/dL (P<.001). Moreover, rates of hypoglycemia (<70 mg/dL) decreased significantly by 41% (P<.001).Conclusion: Quality metrics of inpatient glycemic control improved significantly after the establishment of the DINGS process within our facility. Prospective controlled studies are needed to confirm a causal association.Abbreviations: DINGS = daily inpatient glycemic survey EMR = electronic medical record HbA1c = glycated hemoglobin ICU = intensive care unit VA = Veterans Affairs     

Dose – response relationship of bevacizumab in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT), a genetic vascular disorder associated with epistaxis and hepatic shunts, is responsible for high-output cardiac failure in rare cases. Bevacizumab, which targets vascular endothelial growth factor, was shown to decrease both cardiac index (CI) and epistaxis duration in HHT patients with severe liver involvement. The relationship between its serum concentration and change in both CI and epistaxis duration was investigated to design the bevacizumab maintenance dosing regimen of future therapeutic studies. Twenty-five HHT patients with dyspnea and high CI were included in a prospective non-comparative study. They received bevacizumab at a dose of 5 mg/kg per infusion every 14 days for a total of 6 injections. The relationships between bevacizumab serum concentration and both CI and epistaxis duration were described using transit compartments and direct inhibition pharmacokinetic-pharmacodynamic models. The performances of different maintenance regimens were evaluated using simulation. Infusions every 3, 2 and one months were predicted to maintain 41%, 45% and 50% of patients with CI <4 L/min/m² at 24 months, respectively. The fraction of patients with <20 min epistaxis per month was predicted to be 34%, 43% and 60%, with infusion every 3, 2 or one months, respectively. Simulations of the effects of different maintenance dosing regimens predict that monthly 5 mg/kg infusions of bevacizumab should allow sustained control of both cardiac index and epistaxis.