Outcomes After Intensive Rehabilitation for Mechanically Ventilated Patients: A Nationwide Retrospective Cohort Study

ObjectiveTo examine the effects of intensive rehabilitation on mortality and liberation from mechanical ventilation among patients with mechanical ventilation in intensive care units.DesignRetrospective cohort study using the Diagnosis Procedure Combination inpatient database.SettingPatients discharged from acute care hospitals from April 2010 to March 2016.ParticipantsPatients (N=46,438) aged 20 years and older who were admitted to intensive care units and who started rehabilitation within 3 days of starting mechanical ventilation.InterventionIntensive rehabilitation in intensive care unit in the first 5 days after admission. Amount of rehabilitation was defined as the average number of units per day in the first 5 days after admission and was dichotomized as intensive (≥1.0 unit/d) or nonintensive (<1.0 unit/d) rehabilitation.Main Outcome MeasuresThe primary outcome was in-hospital mortality. The secondary outcome was liberation from mechanical ventilation.ResultsWe identified 29,982 eligible patients, including intensive (n=7745) and nonintensive (n=22,237) rehabilitation groups. In the propensity score-matched analysis, the intensive rehabilitation group had significantly lower in-hospital mortality (risk difference: ?3.4%; 95% CI, ?4.9% to ?1.9%) and a higher proportion of liberation from mechanical ventilation (subdistribution hazard ratio, 1.08; 95% CI, 1.03-1.13) compared with the nonintensive rehabilitation group.ConclusionsPatients receiving a higher amount of rehabilitation in intensive care units were less likely to die and more likely to be liberated from mechanical ventilation.     

Comparison of three block bone substitutes for bone regeneration: long-term observation in the beagle dog

This study aimed to evaluate the impact of three types of block bone substitute material on bone formation and graft resorption in vivo. Standardized bone defects (n?=?4 defects/animal) were created in the calvaria of nine dogs. Block bone substitutes made of deproteinized bovine bone mineral (DBBM), beta-tricalcium phosphate (β-TCP) and a mixture alpha-TCP and hydroxyapatite (α-TCP/HA) were inserted into the bone defects. A fourth defect was left untreated (empty). All sites were covered with a collagenous membrane. Block biopsies were harvested at 3, 6 and 12 months post-implantation and analyzed by micro-CT and histology. Biomaterial absorption was minimal and incorporation within the defect margin was good for all biomaterials. However, β-TCP demonstrated a relatively greater volume of new bone formation and less residual material volume when compared with DBBM and α-TCP/HA. Conversely, α-TCP/HA showed higher osteoconductive potential and a greater new bone area compared with the other two biomaterials. The block bone substitutes used in the present in vivo study showed advantageous in terms of maintenance of their original form in bony defect. However, the positive impact of all biomaterials on new bone formation and replacement of bone was minor even at 12 months. These findings indicate that block bone substitutes are not well suited to vertical bone augmentation. Further investigations are required to improve the insufficient new bone volume for promising clinical results.     

The predominance of type I oligosaccharides is a feature specific to human breast milk

Human milk and colostrum contain ～12-13 g/L and ～22-24 g/L of oligosaccharides, respectively. The chemical structures of >100 human milk oligosaccharides (HMO) have been characterized to date. We determined the concentrations of 10 neutral and 9 acidic colostrum HMO collected during the first 3 d of lactation by using reverse phase HPLC after derivatization with 2-aminopyridine or 1-methyl-3-phenyl-5-pyrazolon. The predominant oligosaccharides were Fuc(α1-2)Gal(β1-4Glc (2'-FL), Fuc(α1-2)Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc (LNFP I), Fuc(α1-2)Gal(β1-3)[Fuc(α1-4)]GlcNAc(β1-3)Gal(β1-4)Glc (LNDFH I), and Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc (LNT), the concentration of each of which was ～1-3 g/L. Because these HMO, other than 2'-FL, all contain the Lacto-N-biose type I structure [Gal(β1-3)GlcNAc], we conclude that HMO containing the type I structure predominate over those containing the N-acetyllactosamine type II structure [Gal(β1-4)GlcNAc]. This appears to be a feature that is specific to humans, because the milk and colostrum of other species, including apes and monkeys, either contain only type II oligosaccharides or type II predominate over type I. It is possible that type I HMO may have importance as substrates for beneficial bifidobacteria in breast-fed infants. The biological importance of type I HMO predominance warrants further study, both in relation to human health and to human evolution.     

Rapid downregulation of cyclin D1 induced by geranylgeranoic acid in human hepatoma cells

Geranylgeranoic acid (GGA) and its derivatives are currently under development as chemopreventive agents against second primary hepatoma in Japan. We aimed to evaluate chemoprevention targets of GGA and a surrogate marker of chemopreventive response to clarify the molecular mechanism of hepatoma chemoprevention with GGA. Human hepatoma-derived cell lines such as HuH-7, PLC/PRF/5, and HepG-2, were treated with GGA and its derivatives. Cellular dynamics of several cell-cycle-related proteins were assessed by either immunoblotting or immunofluorescence method. The cellular expression of cyclin D1 protein was suppressed immediately after GGA treatment. This reduction was partially blocked by pretreatment with 26S proteasome inhibitor MG-132, indicating that proteasomal degradation was involved in GGA-induced disappearance of cyclin D1. A phosphorylation of retinoblastoma protein (RB) at serine 780, a target site of cyclin D1-dependent kinase 4, was rapidly decreased in GGA-treated HuH-7 cells. Furthermore, subcellular fractionation, Western blotting, and immunofluorescence revealed GGA-induced nuclear accumulation of RB. These results strongly suggest that cyclin D1 may be a target of chemopreventive GGA in human hepatoma cells. GGA-induced rapid repression of cyclin D1, and a consequent dephosphorylation and nuclear translocation of RB, may influence cell cycle progression and may be relevant to GGA-induced cell death mechanisms.     

Endogenous glutamine production in critically ill patients: the effect of exogenous glutamine supplementation

Introduction

Glutamine rate of appearance (R_a) may be used as an estimate of endogenous glutamine production. Recently a technique employing a bolus injection of isotopically labeled glutamine was introduced, with the potential to allow for multiple assessments of the glutamine R_a over time in critically ill patients, who may not be as metabolically stable as healthy individuals. Here the technique was used to evaluate the endogenous glutamine production in critically ill patients in the fed state with and without exogenous glutamine supplementation intravenously.

Methods

Mechanically ventilated patients (n = 11) in the intensive care unit (ICU) were studied on two consecutive days during continuous parenteral feeding. To allow the patients to be used as their own controls, they were randomized for the reference measurement during basal feeding without supplementation, before or after the supplementation period. Glutamine R_a was determined by a bolus injection of ¹³C-glutamine followed by a period of frequent sampling to establish the decay-curve for the glutamine tracer. Exogenous glutamine supplementation was given by intravenous infusion of a glutamine containing dipeptide, L-alanyl-L-glutamine, 0.28 g/kg during 20 hours.

Results

A 14% increase of endogenous glutamine R_a was seen at the end of the intravenous supplementation period as compared to the basal measurements (P = 0.009).

Conclusions

The bolus injection technique to measure glutamine R_a to estimate the endogenous production of glutamine in critically ill patients was demonstrated to be useful for repetitive measurements. The hypothesized attenuation of endogenous glutamine production during L-alanyl-L-glutamine infusion given as a part of full nutrition was not seen.