Liver-related events after direct-acting antiviral therapy in patients with hepatitis C virus-associated cirrhosis

Journal of Gastroenterology - Direct-acting antiviral (DAA) therapy enables a high rate of sustained virologic response (SVR) in patients with hepatitis C virus associated cirrhosis. However, the...     

Post-treatment cell-free DNA as a predictive biomarker in molecular-targeted therapy of hepatocellular carcinoma

Journal of Gastroenterology - Liquid biopsies, particularly those involving circulating tumor DNA (ctDNA), are rapidly emerging as a non-invasive alternative to tumor biopsies. However, clinical...     

Subcutaneous adipose 11 beta-hydroxysteroid dehydrogenase type 1 activity and messenger ribonucleic acid levels are associated with adiposity and insulinemia in Pima Indians and Caucasians

Metabolic effects of cortisol may be critically modulated by glucocorticoid metabolism in tissues. Specifically, active cortisol is regenerated from inactive cortisone by the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11-HSD1) in adipose and liver. We examined activity and mRNA levels of 11-HSD1 and tissue cortisol and cortisone levels in sc adipose tissue biopsies from 12 Caucasian (7 males and 5 females) and 19 Pima Indian (10 males and 9 females) nondiabetic subjects aged 28 +/- 7.6 yr (mean +/- SD; range, 18-45). Adipose 11-HSD1 activity and mRNA levels were highly correlated (r = 0.51, P = 0.003). Adipose 11-HSD1 activity was positively related to measures of total (body mass index, percentage body fat) and central (waist circumference) adiposity (P < 0.05 for all) and fasting glucose (r = 0.43, P = 0.02), insulin (r = 0.60, P = 0.0005), and insulin resistance by the homeostasis model (r = 0.70, P < 0.0001) but did not differ between sexes or ethnic groups. Intra-adipose cortisol was positively associated with fasting insulin (r = 0.37, P = 0.04) but was not significantly correlated with 11-HSD1 mRNA or activity or with other metabolic variables. In this cross-sectional study, higher adipose 11-HSD1 activity is associated with features of the metabolic syndrome. Our data support the hypothesis that increased regeneration of cortisol in adipose tissue influences metabolic sequelae of human obesity.     

CD34+ cell dose and hematologic recovery in allogeneic peripheral blood stem cell transplantation

Allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) has been performed as an alternative to bone marrow transplantation (BMT). Here we report poor mobilization with granulocyte-colony stimulating factor (G-CSF) and engraftment kinetics in Allo-PBSCT. Sixteen patients (aged 6-61 yr, median 34 yr) received allogeneic peripheral blood stem cells from related donors (aged 15-68 yr, median 37 yr) after myeloablative therapy. Nine of the patients had standard-risk disease and 7 had high-risk disease. The donors received G-CSF at a dose of 10 micrograms/kg/day by subcutaneous injection for 4 to 6 days. Peripheral blood stem cells were subsequently collected in 1 to 3 aphereses and infused immediately. All patients received G-CSF after transplantation. Fifteen patients underwent Allo-PBSCT and one underwent Allo-PBSCT plus BMT. The mean number of CD34+ cells infused in the 15 Allo-PBSCT patients was 6.32 x 10(6)/kg (range 1.28-14.20). The outcomes were compared with 9 identically treated patients who underwent Allo-BMT. The median times until engraftment for neutrophils > 500/microliter and platelets > 20,000/microliter were 14 (range 10-17) and 15 (range 11-50) days in the Allo-PBSCT group and 17 (range 13-29) and 20 (range 16-160) days in the Allo-BMT group, respectively (p = 0.0177 and p = 0.003). Three donors were considered to have poor mobilization (< 2 x 10(6) CD34+ cells/kg of the recipient); two of them yielded 1.28 and 1.78 x 10(6) CD34+ cells/kg in 3 apheresis procedures. The patients who received cells from these donors showed prompt neutrophil engraftment, but one showed delayed platelet engraftment and another died of grade IV acute GVHD before reaching 20,000 platelets/microliter. An additional bone marrow harvest was necessary from one donor because of poor mobilization(0.17 x 10(6) CD34+ cells/kg). Thus, Allo-PBSCT results in more rapid engraftment. It will be necessary to clarify the minimum CD34+ cell dose for complete engraftment in a larger series of trials.     

Evaluation of salvaged myocardium after acute myocardial infarction using single photon emission computed tomography after 201Tl-glucose-insulin infusion.

BACKGROUND: GIK-201Tl imaging reportedly improves the detection of viable myocardium, so the present study evaluated whether it can detect myocardial viability after acute myocardial infarction (AMI). METHODS AND RESULTS: Resting 201Tl and 99mTc-pyrophosphate (PYP) dual single photon emission computed tomography (SPECT) and 201Tl SPECT after 201Tl with GIK (10% glucose, insulin 5 U, and KCl 10 mmol) infusion (GIK-201Tl) were performed in 25 AMI patients within 10 days of admission. GIK-201Tl SPECT images were obtained immediately and 4 h after infusion. Left ventriculography (LVG) was performed within 3 weeks and at 6 months when follow-up 201Tl SPECT was also performed. From 20 SPECT segments, both the summed defect score (RDS) and the number of defect segments (ES) were calculated. The infarcted area was defined as 99mTc-PYP uptake segments. Wall motion was estimated in 7 LVG segments. The ES of R-201Tl (5.5 +/- 2.8), immediate GIK-201Tl (4.0 +/- 2.3), and 4-h GIK-201Tl (5.6 +/- 2.7) were lower than that of 99mTc-PYP (7.5 +/- 4.1) (p<0.05), and the ES had significantly declined 6 months later on 201Tl (3.5 +/- 2.8) (p<0.05). Although the RDS of R-201Tl (11.3 +/- 7.9) and 4-h GIK-201Tl (11.2 +/- 6.3) were greater than at the 6-month 201Tl (7.1 +/- 6.5), immediate GIK-201Tl (7.4 +/- 6.5) was equivalent to follow-up 201Tl. The sensitivity of immediate GIK-201Tl was highest among the imaging methods. CONCLUSION: To detect myocardial viability after AMI, early imaging with GIK-201Tl is more useful than resting 201Tl imaging.     

Severe Hyperglycemia Immediately After Allogeneic Hematopoietic Stem-Cell Transplantation is Predictive of Acute Graft-Versus-Host Disease

Stress hyperglycemia and acute graft-versus-host disease (GVHD), the major early complication of hematopoietic stem cell transplantation (HSCT), are both associated with excessive release of inflammatory cytokines. We investigated whether new-onset hyperglycemia immediately after HSCT predicts acute GVHD. We studied nondiabetic adult recipients of human leukocyte antigen-matched HSCT (peripheral blood stem cells) for acute leukemia. Using mean morning serum glucose on Days 1–10, we classified hyperglycemia as: mild (6.11–8.33 mmol/L), moderate (8.34–9.98), and severe (minimum of 9.99). Subjects who were GVHD‐free on Day 10 were followed during Days 11–100 for grades II–IV acute GVHD or competing event. Evaluation utilized cumulative incidence-based proportional hazards regression. Subjects (n?=?328) were age 18–74, median of 49 years. Per body mass index (BMI)—25.0 % were obese (BMI, 30–48), 33.8 % overweight (25 to <30), 30.8 % normal weight (21 to <25), and 10.4 % lean (18 to <21). Mild, moderate, or severe hyperglycemia occurred during Days 1–10 in 50.0, 21.3, and 16.8 % of subjects, respectively. Cumulative incidence on Day 100 was 44.8 (±2.8)?% acute GVHD and 7.9 (±1.5)?% competing event. Among normal-to-overweight subjects (n?=?212), severe hyperglycemia developed in 14.2 % (n?=?30) and more than doubled the risk of acute GVHD (hazards ratio, 2.71; 95 % CI, 1.58–4.65—adjusted for donor/recipient characteristics, prophylactic regimen, and mucositis). In contrast, among obese subjects (n?=?82), severe hyperglycemia developed in 30.5 % (n?=?25) but did not significantly affect risk of GVHD. (No lean subjects (n?=?34) developed severe hyperglycemia.) Hyperglycemia that was less than severe had an effect indistinguishable from normoglycemia. In nondiabetic patients, severe hyperglycemia immediately after allogeneic HSCT indicates increased likelihood of acute GVHD. This association is absent in obese patients, who may be primed by obesity-induced inflammation to develop severe hyperglycemia even without experiencing the cytokine storm that is essential to GVHD pathogenesis.     

Characteristics of gram-negative bacteremia during febrile neutropenia among allogeneic hematopoietic stem cell transplant recipients on levofloxacin prophylaxis

European Journal of Clinical Microbiology & Infectious Diseases - The aim of this study is to clarify the characteristics of gram-negative bacteremia (GNB), including extended-spectrum...     

Disseminated tuberculosis following reduced-intensity cord blood transplantation for adult patients with hematological diseases

Allogeneic hematopoietic stem cell transplantation (allo-SCT) recipients are prone to infections. The incidences of mycobacterial infections after allo-SCT in several case series vary from less than 0.1-5.5%. However, no study has been published on tuberculosis following unrelated cord blood transplantation (UCBT). We retrospectively reviewed medical records of 113 adult patients with a median age of 54 years who underwent reduced-intensity UCBT (RI-UCBT) at Toranomon Hospital from March 2002 to May 2004. Mycobacterium tuberculosis infections were diagnosed in three patients (2.7%), of these two patients developed primary infection and one patient developed reactivation of latent tuberculosis. The interval between RI-UCBT and the diagnosis of tuberculosis was 34, 41 and 61 days. All the patients had disseminated disease at diagnosis. Histological examination showed the lack of granuloma in caseous necrosis. Combination antituberculous treatments showed limited efficacy, and two patients died immediately after diagnosis. M. tuberculosis caused life-threatening illness, rapidly progressing in RI-UCBT recipients. The lack of granuloma in caseous necrosis suggests the impaired T-cell function in early post transplant phase of RI-UCBT. We should consider M. tuberculosis in the differential diagnoses of fever of unknown source after RI-UCBT.     

Non-linear association between ankle-brachial pressure index and prevalence of silent cerebral infarction in Japanese patients with type 2 diabetes

ObjectivePatients with peripheral artery disease (PAD), defined as having low ankle-brachial pressure index (ABI), have increased risk for incident stroke compared with those without PAD. We aimed to reveal whether ABI abnormality, especially high ABI is associated with prevalent silent cerebral infarction (SCI) in type 2 diabetic patients.MethodsWe studied 538 Japanese type 2 diabetic patients, 227 women and 311 men, with a mean [±SD] age of 64 ± 11 years. All patients underwent cranial magnetic resonance imaging (MRI). Values of ABI were classified as low (<0.9), normal (0.9≤ and <1.3), and high (1.3≤). Logistic regression model was used to calculate odds ratio and 95% confidence interval (95% CI) for prevalent SCI.ResultsThe mean ABI among the overall 538 patients was 1.09 ± 0.16. Low and high ABI values were found in 52 (9.7%) and 33 (6.1%) patients, respectively. SCI was detected in 297 (55.2%) patients. The prevalence in patients with low, normal, and high ABI values were 88.5%, 49.7%, and 78.8 (p < 0.001), respectively. In the multivariate logistic regression analysis, both patients with high and low ABI were significantly increased risk of prevalent SCI (odds ratio 4.53, 95% CI 1.67–12.34, p = 0.003 and odds ratio 3.50, 95% CI 1.50–10.29, p = 0.005), independently of other traditional cardiovascular risk factors, than those with normal ABI.ConclusionsBoth high and low ABI may be strongly associated with prevalent SCI in Japanese patients with type 2 diabetes.