Fat-free mass at admission predicts 28-day mortality in intensive care unit patients: the international prospective observational study Phase Angle Project

Purpose

Phase angle as measured by bioelectrical impedance analysis reflects fat-free mass. Fat-free mass loss relates to worse prognosis in chronic diseases. Primary aim of this study was: to determine the association between fat-free mass at intensive care unit admission and 28-day mortality.

Methods

Ten centres in nine countries participated in this multicentre prospective observational study. The inclusion criteria were age >18 years; expected length of stay >48 h; absence of pacemaker, heart defibrillator implant, pregnancy and lactation. Fat-free mass was assessed by measurement of the 50-kHz phase angle at admission. The primary endpoint was 28-day mortality. The area under the receiver operating characteristic curve (AUC) was used to assess prediction of 28-day mortality by fat-free mass at ICU admission. The variables associated with 28-day mortality were analysed by means of multivariable logistic regression.

Results

Of the 3605 patients screened, 931 were analysed: age 61 ± 16 years, male 60 %, APACHE II 19 ± 9, body mass index 26 ± 6, day 1 phase angle 4.5° ± 1.9°. Day 1 phase angle was lower in patients who eventually died than in survivors (4.1° ± 2.0° vs. 4.6° ± 1.8°, P = 0.001). The day 1 phase angle AUC for 28-day mortality was 0.63 [0.58–0.67]. In multivariable analysis, the following were independently associated with 28-day mortality: age (adjusted odds ratio (aOR) 1.014 [95 % confidence interval 1.002–1.027], P = 0.03), day 1 phase angle (aOR 0.86 [0.78–0.96], P = 0.008), APACHE II (aOR 1.08 [1.06–1.11], P < 0.001), surgical patient (aOR 0.51 [0.33–0.79], P = 0.002), and admission for other diagnosis (aOR 0.39 [0.21–0.72], P = 0.003). A multivariable combined score improved the predictability of 28-day mortality: AUC = 0.79 [0.75–0.82].

Conclusion

Low fat-free mass at ICU admission is associated with 28-day mortality. A combined score improves mortality predictability. Trial registration: NCT01907347 (http://www.clinicaltrials.gov).

     

Depression in perinatally HIV-infected pregnant women compared to non-perinatally HIV-infected and HIV-uninfected pregnant women

“Depression (as noted in chart by a physician)” was compared between HIV infected pregnant women and controls. Perinatally HIV-infected (PHIV), non-perinatally HIV-infected (NPHIV), and HIV-uninfected (HIV-U) pregnant women were all compared using a logistic regression model. Overall, HIV-infected women had higher rates of depression than HIV-U, with PHIV women demonstrating a clinically and statistically significant increased risk compared to HIV-U women [adjusted OR: 15.9, 95% CI?=?1.8–143.8]. Future studies in larger populations are warranted to confirm these findings and further elucidate mental health outcomes of PHIV and NPHIV pregnant women.     

The case for a medication first approach to the treatment of opioid use disorder

Background: The opioid addiction and overdose crisis continues to ravage communities across the U.S. Maintenance pharmacotherapy using buprenorphine or methadone is the most effective intervention for Opioid Use Disorder (OUD), yet few have immediate and sustained access to these medications. Objectives: To address lack of medication access for people with OUD, the Missouri Department of Mental Health began implementing a Medication First (Med First) treatment approach in its publicly-funded system of comprehensive substance use disorder treatment programs. Methods: This Perspective describes the four principles of Med First, which are based on evidence-based guidelines. It draws conceptual comparisons between the Housing First approach to chronic homelessness and the Med First approach to pharmacotherapy for OUD, and compares state certification standards for substance use disorder (SUD) treatment (the traditional approach) to Med First guidelines for OUD treatment. Finally, the Perspective details how Med First principles have been practically implemented. Results: Med First principles emphasize timely access to maintenance pharmacotherapy without requiring psychosocial services or discontinuation for any reason other than harm to the client. Early results regarding medication utilization and treatment retention are promising. Feedback from providers has been largely favorable, though clinical- and system-level obstacles to effective OUD treatment remain. Conclusion: Like the Housing First model, Medication First is designed to decrease human suffering and activate the strengths and capacities of people in need. It draws on decades of research and facilitates partnerships between psychosocial and medical treatment providers to offer effective and life-saving care to persons with OUD.     

Evaluation of IGF-1 concentration in serum and synovial fluid in women with different type coxarthrosis]

Osteoarthritis is the greatest problem of aging population. It concerns particularly women over 65 years of age, in considerable degree limiting their locomotion activity. In recent years many different opinions on pathogenesis of osteoarthritis were presented, among them on the role of some growth factors like IGF-1 and TGF-beta playing an anabolic role in cartilage metabolism. The aim of our study was to compare the concentration of IGF-1 in clinically healthy women and women with coxarthrosis and to evaluate the association between IGF-1 in the serum and synovial fluid in relation to disease etiology. We found that in coxarthrosis of either idiopathic, necrotic or dysplastic etiology serum IGF-1 level was significantly lower than in control women (84.4; 76.1; 86.7 vs. 147.7 microg/ml). Concentration of IGF-1 in different groups of patients was similar or lower in synovial fluid than in the serum. Consistently decreased IGF-1 was found in synovial fluid (42.3 microg/ml) of patients with coxarthosis of necrotic origin. Our results suggest that low IGF-1 values, especially in synovial fluid, are in association with type of osteoarthritic changes within the joint, independently on age.     

Phase II preclinical drug screening in human tumor xenografts: a first European multicenter collaborative study.

In a European joint project carried out in 6 laboratories a disease-oriented program was set up consisting of a panel of 7 tumor types, each represented by 4 to 8 different human tumor lines, for secondary screening of promising anticancer drugs. Human tumor lines were selected on the basis of differences in histology, growth rate, and sensitivity to conventional cytostatic agents. Xenografts were grown s.c. in nude mice, and treatment was started when tumors reached a mean diameter of 6 mm in groups of mice where at least 6 tumors were evaluable. Drugs were given at the maximum tolerated dose. For evaluation of drug efficacy, median tumor growth curves were drawn, and specific growth delay and treated/control x 100% were calculated. Doxorubicin (8 mg/kg i.v. days 1 and 8) was effective (treated/control < 50%, and specific growth delay > 1.0) in 0 of 2 breast cancers, 1 of 3 colorectal cancers, 2 of 5 head and neck cancers, 3 of 6 non-small cell lung cancers, 4 of 6 small cell lung cancers, 0 of 3 melanomas, and 3 of 6 ovarian cancer lines. Amsacrine (8 mg/kg i.v. days 1 and 8) was not effective, while datelliptium (35 mg/kg i.p. days 1 and 8) was active against 2 of 6 small cell lung cancer lines. Brequinar sodium (50 mg/kg i.p. days 1-5) showed efficacy in 4 of 5 head and neck cancers, 5 of 8 non-small cell lung cancers, and 4 of 5 small cell lung cancer lines. The project has been shown to be a feasible approach. Clinical activity for doxorubicin and inactivity for amsacrine against solid tumor types was confirmed in the human tumor xenograft panel. Additional anticancer drugs will be studied in the European joint project to further define the reliability of this novel, promising screening approach.     

The regulation of integrin-mediated osteoblast focal adhesion and focal adhesion kinase expression by nanoscale topography

An important consideration in developing physical biomimetic cell-stimulating cues is that the in vivo extracellular milieu includes nanoscale topographic interfaces. We investigated nanoscale topography regulation of cell functions using human fetal osteoblastic (hFOB) cell culture on poly(l-lactic acid) and polystyrene (50/50 w/w) demixed nanoscale pit textures (14, 29, and 45nm deep pits). Secondary ion mass spectroscopy revealed that these nanotopographic surfaces had similar surface chemistries to that of pure PLLA because of PLLA component surface segregation during spin casting. We observed that 14 and 29nm deep pit surfaces increased hFOB cell attachment, spreading, selective integrin subunit expression (e.g., alphav relative to alpha5, beta1, or beta3), focal adhesive paxillin protein synthesis and paxillin colocalization with cytoskeletal actin stress fibers, and focal adhesion kinase (FAK) and phosphorylated FAK (pY397) expression to a greater degree than did 45nm deep pits or flat PLLA surfaces. Considering the important role of integrin-mediated focal adhesion and intracellular signaling in anchorage-dependent cell function, our results suggest a mechanism by which nanostructured physical signals regulate cell function. Modulation of integrin-mediated focal adhesion and related cell signaling by altering nanoscale substrate topography will have powerful applications in biomaterials science and tissue engineering.     

Comparing the young asthmatics running fitness

INTRODUCTION: Nowadays, doctors strongly recommend physical activity for asthmatic children, since the resulting improved physical fitness and psychological change also raise the quality of life. AIMS: The aim of this study was to compare the physical fitness of asthmatic children who regularly participate in therapeutic swimming, with asthmatic children who do not participate in this training and with non-swimming, healthy children using the 12 minute free running, Cooper test. METHOD: The children from the swimmer asthmatic group (n= 51, age = 9-22 yrs) took part in a special, long term, swimming exercise program (Gyene method). Whereas, the non-swimmer asthmatics (n = 28, age = 8-22 yrs) and the healthy children (n: 179, age: 9-22 yrs) only took part in the normal school physical education classes. Fitness was measured using the Cooper test. RESULTS: Data was collected from 258 subjects and showed that the fitness of swimmer asthmatics is significantly better than that of the non-swimmer asthmatics and even better than that of the healthy subjects (swimmer/ non swimmer asthmatic p = 0.01; swimmer asthmatic/ healthy p < 0.0001 Chi(2) test). The difference in the fitness acquired from swimming was the most pronounced for the 8-11 years old asthmatics, presumably because of greater motivational factors. No differences were found between genders for the two asthmatic groups, whereas healthy boys were found to have significantly greater levels of fitness than healthy girls. CONCLUSIONS: Fitness is substantially increased with regular swimming. The favourable effects of swimming are expressed not only in comparison with the non-swimmer asthmatics but with the healthy subjects too. The regular therapeutic swimming program helps the formation of running fitness too.     

Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases

Cathelicidin LL-37 is one of the few human bactericidal peptides with potent antistaphylococcal activity. In this study we examined the susceptibility of LL-37 to proteolytic degradation by two major proteinases produced by Staphylococcus aureus, a metalloproteinase (aureolysin) and a glutamylendopeptidase (V8 protease). We found that aureolysin cleaved and inactivated LL-37 in a time- and concentration-dependent manner. Analysis of the generated fragments by mass spectroscopy revealed that the initial cleavage of LL-37 by aureolysin occurred between the Arg19-Ile20, Arg23-Ile24, and Leu31-Val32 peptide bonds, instantly annihilating the antibacterial activity of LL-37. In contrast, the V8 proteinase hydrolyzed efficiently only the Glu16-Phe17 peptide bond, rendering the C-terminal fragment refractory to further degradation. This fragment (termed LL-17-37) displayed antibacterial activity against S. aureus at a molar level similar to that of the full-length LL-37 peptide, indicating that the antibacterial activity of LL-37 resides in the C-terminal region. In keeping with LL-37 degradation by aureolysin, S. aureus strains that produce significant amounts of this metalloprotease were found to be less susceptible to LL-17-37 than strains expressing no aureolysin activity. Taken together, these data suggest that aureolysin production by S. aureus contributes to the resistance of this pathogen to the innate immune system of humans mediated by LL-37.