Comparisons of Metabolic Load between Adaptive Support Ventilation and Pressure Support Ventilation in Mechanically Ventilated ICU Patients.

Purpose: The aim of this study was to compare the metabolic load between adaptive support ventilation (ASV) and pressure support ventilation (PSV) modes in critically ill patients. Methods: Sequential 20 min ventilation by PSV followed by 20 min ASV in critically ill patients was assessed. ASV was set for full support, i.e., with the minute volume control set at the same level as the minute volume observed during PSV. The trial started from PSV 8 cmH2O and continued with high (PSV 12 cmH2O) to low (PSV 0) conditions or low to high conditions, in random order. The oxygen consumption (VO2), production of carbon dioxide (VCO2), and energy expenditure (EE) were measured by indirect calorimetry (IC). Results: Twenty-four patients with critical illness participated in the study. Comparing with the PSV mode, the EE in the ASV mode was lower in the level of PSV 0 cmH2O (1069 ± 73 vs. 1425 ± 76 kcal), PS 8 cmH2O (1116 ± 70 vs. 1284 ± 61 kcal), and PS 12 cmH2O (1017 ± 70 vs. 1169 ± 58 kcal) (p < 0.05). The VO2, VCO2, and P0.1 in PSV were significantly higher than those in ASV (p < 0.05). The VO2, VCO2, and P0.1 in PSV were significantly higher than those in ASV (. Conclusion: In patients with critical illness, the application of ASV set for full support was associated with a lower metabolic load and respiratory drive than in any of the studied PSV conditions.

Pneumococcal vaccination and efficacy in patients with heterotaxy syndrome.

BackgroundPneumococcal vaccines, including pneumococcal polysaccharide vaccine (PPV) and pneumococcal conjugated vaccine (PCV), are crucial in preventing invasive pneumococcal diseases. We analyzed the pneumococcal vaccination rate, efficacy, and durability in patients with heterotaxy.MethodsAll patients with heterotaxy and CCHD who were followed up at our institution between 2010 and 2015 were included. Pneumococcal vaccine status and geometric mean concentration (GMC) of serotypes 6B, 14, 19F, and 23F were analyzed. Splenic function was considered abnormal when the percentage of IgM memory B cell was less than 1%.ResultsThe GMCs of the four serotypes did not differ significantly between patients with heterotaxy and those with CCHD; the GMCs were also not affected by abnormal splenic function. Most patients had GMCs >0.35 µg/ml (protection level) 4-5 years after either PPV or PCV injection; however, it may decay gradually in some serotypes. In addition, 21.4% of 42 patients with heterotaxy did not receive pneumococcal vaccine, and none completely adhered to the vaccine guidelines.ConclusionsVaccine efficacy was acceptable, even in patients with abnormal splenic function. In some patients, the durability of PPV and PCV decreased with time, highlighting the importance of booster doses. Vaccination rate in patients with heterotaxy is unsatisfactory.

Low immunoglobulin M memory B-cell percentage in patients with heterotaxy syndrome correlates with the risk of severe bacterial infection.

BACKGROUND: Patients with heterotaxy syndrome, commonly associated with complex congenital heart disease (CHD), exhibit a higher risk of severe bacterial infection (SBI). We sought to define the change of a novel immunologic marker, the immunoglobulin M (IgM) memory B-cell percentage, and its association with SBI. METHODS: We enrolled 46 (M/F 29/17) heterotaxy syndrome patients (42 right atrial isomerism (RAI) and 4 left atrial isomerism (LAI)) aged > 1 y during the period 2010-2012 in a tertiary care center. We analyzed IgM(+)CD27(+) memory B-cell percentages. Patients with simple and complex CHD served as controls. RESULTS: The mean IgM memory B-cell percentages were the lowest in the heterotaxy syndrome group, compared with those in complex and simple CHD groups (1.8 ± 2.1 vs. 3.9 ± 3.2 vs. 5.1 ± 4.7, P < 0.001). In the heterotaxy syndrome group, 41.3% had low IgM memory B-cell percentages (<1% of B cells). Seven had a history of community-acquired SBI and 85.7% of these had low IgM memory B-cell percentages, which was the only significant factors related to community-acquired SBI (P = 0.028). CONCLUSION: The memory B cell and IgM memory B-cell percentages are low in patients with heterotaxy syndrome, and the presence of IgM memory B-cell percentage < 1% correlates with community-acquired SBI.

Cytotoxic effect of s-petasin and iso-s-petasin on the proliferation of human prostate cancer cells.

BACKGROUND: Petasin (Petasides hybridus) is a perennial shrub that is found in Europe as well as parts of Asia and North America and is being used to treat hypertension, tumors and asthma. In a previous study, we reported that petasin possesses biological effects including inhibition of testosterone production and the release of corticosterone from rat zona fasciculata-reticularis cells, and anti-proliferative effect on human T24 bladder carcinoma cells. MATERIALS AND METHODS: In the present study, we assessed the effects of S-petasin and iso-S-petasin on the growth and proliferation of two hormone-independent DU145 and PC3 and one hormone-dependent LNCaP prostate cancer cell line at concentrations of 10(-7)-10(-5) mol/l. The cell proliferation index, cell number index, expression of caspases and apoptosis-associated proteins and cell morphology were measured. RESULTS: S-Petasin and iso-S-petasin reduced the viable cell number and increased the numbers of apoptotic cells in the tested cell lines in a dose-dependent manner. Western blot analysis revealed that S-petasin and iso-S-petasin reduced the protein levels of procaspase 3, 8, and 9 and cleaved poly(ADP-ribose) polymerase (PARP) in all tested prostate cancer cell lines, and reduced that of procaspase 7 in LNCaP and PC3 cells. At the same time, S-petasin and iso-S-petasin increased mitochondrial membrane permeability and cytochrome c release from mitochondria to the cytosol via reducing the ratio of BCL2/BAX in DU145 and PC3 cells, and up-regulating the levels of p53 in DU145 cells but down-regulating it in PC3 cells. CONCLUSION: These results indicate that S-petasin and iso-S-petasin induce apoptosis via the activation of mitochondria-related pathways in prostate cancer cells, suggesting S-petasin and iso-S-petasin could be potential anticancer agents.

Coexisting mutations/polymorphisms of the long QT syndrome genes in patients with repaired Tetralogy of Fallot are associated with the risks of life-threatening events.

Coexisting long QT gene mutations/polymorphisms in Tetralogy of Fallot (TOF) patients may aggravate the repolarization abnormality from cardiac repair. We investigated the impact of these genes on the risk of life-threatening events. Genetic variants of the three common long QT genes were identified from patients with repaired TOF. Life-threatening events were defined as sudden cardiac death and hemodynamic unstable ventricular arrhythmia. Biophysical characterization of the alleles of the genetic variants was performed using a whole-cell voltage clamp with expression in Xenopus oocytes. A total of 84 patients (56.0 % male with 1,215 patients-year follow-up) were enrolled. Six rare variants and six non-synonymous single nucleotide polymorphisms (SNPs) were found in 40 (47.6 %) patients. Life-threatening events occurred in five patients; four received implantable cardioverter defibrillator and one died of sudden cardiac death. Life-threatening events occurred more often in those with genetic variants than those without (5/40 vs. 0/44, P = 0.021); particularly, the hERG or SCN5A gene mutations/polymorphisms (2/5 vs. 3/79, P = 0.027 and 5/27 vs. 0/57, P = 0.003, respectively). Among the five patients with life-threatening events, three had compound variants (hERG p.M645R/SCN5A p.R1193Q, hERG p.K897T/SCN5A p.H558R, and KVLQT1 p.G645S/SCN5A p.P1090L), that also increased the risk of events. Their QTc and JTc were all prolonged. Functional study of the novel variant (hERG gene p.M645R) from patients with life-threatening events revealed a dominant negative effect. In conclusion, in repaired TOF patients, coexisting long QT mutations/polymorphisms might have additive effects on the repolarization abnormality from surgery and thereby increase the risks of life-threatening events.