The purpose of this study was to evaluate the clinical usefulness of static and dynamic variables for the prediction of fluid responsiveness in children under general anaesthesia.
Thirty-three ...mechanically ventilated children received 10 ml kg−1 colloid for 10 min while stable during surgery. Arterial pressure, heart rate, central venous pressure (CVP), and pleth variability index (PVI), in addition to variation in systolic pressure, pulse pressure (including Δdown and Δup), respiratory aortic blood flow velocity (ΔVpeak), and inferior vena cava diameter were measured before and after volume expansion. Patients were classified as responders to fluid loading if their stroke volume index (SVI) increased by at least 10%.
There were 15 volume responders and 18 non-responders. Of the variables examined, ΔVpeak (r=0.516, P=0.004) and PVI (r=0.49, P=0.004) before volume expansion were significantly correlated with changes in SVI. The receiver-operating characteristic (ROC) curve analysis showed that PVI and ΔVpeak predicted fluid responsiveness. Areas under the ROC curves of PVI and ΔVpeak were statistically larger than that of CVP (P=0.006 and 0.014, respectively). However, those of other variables were similar to that of CVP.
ΔVpeak and PVI can be used to predict fluid responsiveness in mechanically ventilated children under general anaesthesia. The other static and dynamic variables assessed in this study were not found to predict fluid responsiveness significantly in children.
ClinicalTrials.gov, NCT01364103.
Summary
Background The treatment of pemphigus is still challenging and some patients with pemphigus are unresponsive to conventional immunosuppressive treatments. Rituximab, a chimeric monoclonal ...anti‐CD20 antibody, binds to the CD20 antigen on the surface of B cells and has been reported to be effective for the treatment of recalcitrant pemphigus.
Objective To compare the efficacy of different doses of rituximab in patients with pemphigus who were unresponsive to conventional therapies.
Methods Twenty‐seven patients with pemphigus who received different doses of rituximab (375 mg m−2 per infusion weekly) were analysed retrospectively. We divided the patients into two groups: group 1 (n = 12) received two infusions of rituximab and group 2 (n = 15) received three or more infusions of rituximab at 1‐week intervals. The number of infusions was determined by the choice of each patient. The endpoints of the study were time to disease control, partial remission (PR) and complete remission (CR).
Results There was no significant difference in time to achieve PR between the two groups (147 vs. 135 days, P = 0·65). However, group 2 demonstrated better outcomes than group 1 in time to CR (443 vs. 149 days, P = 0·06) and relapse rate (0% vs. 67%, P < 0·01).
Conclusions We conclude that three or more infusions of rituximab are more effective than two infusions for the treatment of pemphigus.
This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer.
Patients with thyroid ...cancer of any histology that was resistant or not appropriate for 131I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate partial response (PR) + stable response ≥12 weeks. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD), progression-free survival (PFS), overall survival, duration of response, and safety.
Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks 95% confidence interval (CI) 14.9–78.5. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%).
Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation.
NCT01164176.
We evaluated whether ELISPOT assay can predict tuberculosis (TB) development in kidney‐transplantation (KT) recipients with a negative tuberculin skin test (TST). All adult patients admitted to a KT ...institute between June 2008 and December 2009 were enrolled; TB development after KT was observed between June 2008 and December 2010. Isoniazid (INH) was given to those patients with positive TST or clinical risk factors for latent TB infection (LTBI). ELISPOT assay was performed on all patients, and TB development after KT was observed by a researcher blinded to the results of ELISPOT. A total of 312 KT recipients including 242 (78%) living‐donor KT were enrolled. Of the 312 patients, 40 (13%) had positive TST or clinical risk factors for LTBI and received INH; none developed TB after KT. Of the remaining 272 patients, 4 (6%) of 71 with positive ELISPOT assay developed TB after KT, whereas none of the 201 patients with negative (n = 171) or indeterminate ELISPOTs (n = 30) developed TB after KT (rate difference between positive and negative/indeterminate ELISPOT, 3.3 per 100 person‐years 95% CI 1.4–5.1, p<0.001). Positive ELISPOT results predict subsequent development of TB in KT recipients in whom LTBI cannot be detected by TST or who lack clinical risk factors for LTBI.
Positive results of an interferon‐gamma releasing assay anticipate the subsequent development of tuberculosis in kidney transplant recipients in whom latent tuberculosis infection cannot be detected by tuberculin skin test or who lack clinical risk factors for latent tuberculosis infection. See editorial by Torre‐Cisneros and Doblas on page 1769.
AIMS: The aim of this study was to evaluate the effects of Bifidobacterium lactis HY8101 on insulin resistance induced using tumour necrosis factor‐α (TNF‐α) in rat L6 skeletal muscle cells and on ...the KK‐AY mouse noninsulin‐dependent diabetes mellitus (NIDDM) model. METHODS AND RESULTS: The treatment using HY8101 improved the insulin‐stimulated glucose uptake and translocation of GLUT4 via the insulin signalling pathways AKT and IRS‐1(Tyr) in TNF‐α‐treated L6 cells. HY8101 increased the mRNA levels of GLUT4 and several insulin sensitivity‐related genes (PPAR‐γ) in TNF‐α‐treated L6 cells. In KK‐AY mice, HY8101 decreased fasting insulin and blood glucose and significantly improved insulin tolerance. HY8101 improved diabetes‐induced plasma total cholesterol and triglyceride (TG) levels and increased the muscle glycogen content. We observed concurrent transcriptional changes in the skeletal muscle tissue and the liver. In the skeletal muscle tissue, the glycogen synthesis‐related gene pp‐1 and GLUT4 were up‐regulated in mice receiving HY8101 treatment. In the liver, the hepatic gluconeogenesis‐regulated genes (PCK1 and G6PC) were down‐regulated in mice receiving HY8101 treatment. CONCLUSIONS: Bifidobacterium lactis HY8101 can be used to moderate glucose metabolism, lipid metabolism and insulin sensitivity in mice and in cells. SIGNIFICANCE AND IMPACT OF THE STUDY: Bifidobacterium lactis HY8101 might have potential as a probiotic candidate for alleviating metabolic syndromes such as diabetes.
ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the ...largest single‐center experience of ABO‐incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in‐hospital mortality. The cumulative 3‐year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO‐compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody‐mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.
This article presents the clinical results of ABO‐incompatible adult living donor liver transplantation in a single institution.
MicroRNAs (miRNAs) have been shown to be major regulators of eukaryotic gene expression. However, bacterial RNAs comparable in size to eukaryotic miRNAs (18–22 nucleotides) have received little ...attention. Recently, a novel class of small RNAs similar in size to miRNAs (miRNA-size, small RNAs or msRNAs) have also been found in several bacteria. Like miRNAs, msRNAs are approximately 15 to 25 nucleotides in length, and their precursors are predicted to form a hairpin loop secondary structure. Here, we identified msRNAs in the periodontal pathogens Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola. We examined these msRNAs using a deep sequencing method and characterized dozens of msRNAs through bioinformatic analysis. Highly expressed msRNAs were selected for further validation. The findings suggest that this class of small RNAs is well conserved across the domains of life. Indeed, msRNAs secreted via bacterial outer membrane vesicles (OMVs) were detected. The ability of bacterial OMVs to deliver RNAs into eukaryotic cells was also observed. These msRNAs in OMVs allowed us to identify their potential human immune-related target genes. Furthermore, we found that exogenous msRNAs could suppress expression of certain cytokines in Jurkat T cells. We propose msRNAs may function as novel bacterial signaling molecules that mediate bacteria-to-human interactions. Furthermore, this study may provide fresh insight into bacterial pathogenic mechanisms of periodontal diseases.
The usefulness of pharmacokinetic parameters for glioma grading has been reported based on the perfusion data from parts of entire-tumor volumes. However, the perfusion values may not reflect the ...entire-tumor characteristics. Our aim was to investigate the feasibility of glioma grading by using histogram analyses of pharmacokinetic parameters including the volume transfer constant, extravascular extracellular space volume per unit volume of tissue, and blood plasma volume per unit volume of tissue from T1-weighted dynamic contrast-enhanced perfusion MR imaging.
Twenty-eight patients (14 men, 14 women; mean age, 49.75 years; age range, 25-72 years) with histopathologically confirmed gliomas (World Health Organization grade II, n = 7; grade III, n = 8; grade IV, n = 13) were examined before surgery or biopsy with conventional MR imaging and T1-weighted dynamic contrast-enhanced perfusion MR imaging at 3T. Volume transfer constant, extravascular extracellular space volume per unit volume of tissue, and blood plasma volume per unit volume of tissue were calculated from the entire-tumor volume. Histogram analyses from these parameters were correlated with glioma grades. The parameters with the best percentile from cumulative histograms were identified by analysis of the area under the curve of the receiver operating characteristic analysis and were compared by using multivariable stepwise logistic regression analysis for distinguishing high- from low-grade gliomas.
All parametric values increased with increasing glioma grade. There were significant differences among the 3 grades in all parameters (P < .01). For the differentiation of high- and low-grade gliomas, the highest area under the curve values were found at the 98th percentile of the volume transfer constant (area under the curve, 0.912; cutoff value, 0.277), the 90th percentile of extravascular extracellular space volume per unit volume of tissue (area under the curve, 0.939; cutoff value, 19.70), and the 84th percentile of blood plasma volume per unit volume of tissue (area under the curve, 0.769; cutoff value, 11.71). The 98th percentile volume transfer constant value was the only variable that could be used to independently differentiate high- and low-grade gliomas in multivariable stepwise logistic regression analysis.
Histogram analysis of pharmacokinetic parameters from whole-tumor volume data can be a useful method for glioma grading. The 98th percentile value of the volume transfer constant was the most significant measure.
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