Persistent inflammation and recovery after intensive care: A systematic review.

PURPOSE: Physical weakness is common after critical illness; however, it is not clear how best to treat it. Inflammation characterizes critical illness, is associated with loss of muscle mass during critical illness, and potentially modifies post-intensive care unit (ICU) recovery. We sought to identify published reports on the prevalence of systemic inflammation after critical illness and its association with physical recovery. METHODS: This is a systematic review of the literature from MEDLINE, EMBASE, CINAHL, CPCI-SSH, and CPCI-S from January 1982 to December 2011. RESULTS: From 7433 references, 207 full-text articles were reviewed, 57 were eligible, and 22 were included. Inflammation was present in most patients at ICU discharge according to C-reactive protein concentration (range, 70%-100%), procalcitonin (range, 89%-100%), tumor necrosis factor α (100%), and systemic inflammatory response syndrome criteria (range, 92%-95%). Fewer patients had elevated myeloperoxidase concentrations (range, 0%-56%). At hospital discharge, 9 (90%) of 10 chronic obstructive pulmonary disease patients had elevated C-reactive protein. No studies tested the association between inflammation and physical recovery. CONCLUSIONS: Inflammation is present in most patients at ICU discharge, but little is known or has been investigated about persistent inflammation after this time point. No studies have explored the relationship between persistent inflammation and physical recovery. Further research is proposed.

Molecular markers of programmed cell death in donor hearts before transplantation.

BACKGROUND: In this study we investigate whether pro-apoptotic, pro-inflammatory and other early signaling markers indicative of increased propensity for cell death processes were evident in human donor heart allografts immediately before transplantation, and whether there is an association with primary graft failure. METHODS: A prospective study was performed utilizing donor left atrial myocardium collected at the time of implantation of hearts from brain-dead donors (BDD, n = 29). In addition, to explore the potential of donor hearts from donation after circulatory death (DCD), myocardial samples were obtained during transplantation of lungs from DCD donors (n = 6). A comparator reference group (n = 7) consisted of left atrial specimens from patients undergoing mitral valve surgery. RESULTS: Significantly raised levels of caspase-3 specific activity, activated hypoxia inducible factor-1 (HIF-1α) and 8-hydroxy-2'-deoxyguanosine were evident in the transplanted hearts (from BDD) that developed primary graft failure (n = 11). DCD hearts did not differ from BDD with regard to mRNA expression levels of FAS, Bax, IL-6 and caspase-3. Although DCD hearts exhibited lower caspase-3 specific activity and activated hypoxia-inducible factor-1 protein, they had higher levels of mRNA for NF-κB, Bnip3 and caspase-1 mRNA. Increased 8-hydroxy-2'-deoxyguanosine levels reflected greater oxidative stress and reactive oxygen species-related DNA fragmentation. CONCLUSIONS: Our data indicate a significant role of pro-apoptotic and pro-inflammatory activity in allografts that subsequently exhibit primary graft failure. The relatively lower levels of apoptotic and inflammatory activity in DCD hearts suggest they may represent a potentially usable donor cardiac allograft pool. This possibility requires further detailed molecular and clinical research.

Asymmetric organocatalytic formation of protected and unprotected tetroses under potentially prebiotic conditions.

Esters of proteinogenic amino acids efficiently catalyse the formation of erythrose and threose under potentially prebiotic conditions in the highest yields and enantioselectivities yet reported. Remarkably while esters of (L)-proline yield (L)-tetroses, esters of (L)-leucine, (L)-alanine and (L)-valine generate (D)-tetroses, offering the potential to account for the link between natural (L)-amino acids and natural (D)-sugars. The effect of pH and NaCl on the yields and enantioselectivities was also investigated and was shown to be significant, with the optimal enantioselectivities occurring at pH 7.

Institution of extracorporeal membrane oxygenation late after lung transplantation - a futile exercise?

The use of and indications for extracorporeal membrane oxygenation (ECMO) are expanding as its reliability improves with widely varying results reported. A retrospective review of 24 lung transplant recipients who required ECMO support postoperatively was performed with 13 patients requiring ECMO within the first 48 h ("early" group) and 11 requiring ECMO after seven d postoperatively ("late" group). The majority of early ECMO group had primary graft failure patients and the late ECMO group comprised patients with infection or non-specific graft failure. There were significant differences in outcomes between groups, with 10/13 in the early group and 4/11 in the late group successfully weaned from ECMO (p = 0.045). Six of the 13 patients in the early group and none of the late group survived to hospital discharge (p = 0.009). The late ECMO group had a much higher incidence of death owing to complications existing prior to institution of ECMO (essentially uncontrolled infection or organ failure). There were no differences in complications arising during ECMO between groups. Late institution of ECMO in lung transplant recipients for causes other than primary graft failure is associated with such poor survival that its use should be considered only in very select cases.

Extracorporeal membrane oxygenation in primary graft failure after heart transplantation.

BACKGROUND: The aim of this review was to analyze our results with extracorporeal membrane oxygenation (ECMO) support for primary graft failure (PGF) in heart transplant recipients. METHODS: A retrospective review of 239 consecutive patients who underwent heart transplantation between January 2000 and August 2009 was performed. Orthotopic, heterotopic, and heart lung transplants were included in this analysis. Over that time period, 54 patients developed PGF, of whom 39 patients required ECMO support. These 39 patients form the basis of this review. RESULTS: Thirty-four patients (87%) were successfully weaned from ECMO and 29 (74.3%) survived to hospital discharge. There were no significant differences in wean rates or complications between central and peripheral ECMO. Comparison of survival in the 39 ECMO patients to the non-PGF patients (n = 185) showed a significantly worse survival in the ECMO group (p = 0.007). When those patients who died in the first 30 days were excluded, there was no difference in overall survival between groups (p = 0.73). CONCLUSIONS: Extracorporeal membrane oxygenation provides excellent circulatory support for patients with PGF after heart transplantation with good wean and survival to discharge rates.

Efficient asymmetric organocatalytic formation of erythrose and threose under aqueous conditions.

Esters of proteinogenic amino acids efficiently catalyse the formation of erythrose and threose under aqueous conditions in the highest yields and enantioselectivities yet reported. Remarkably while esters of (L)-proline yield (L)-carbohydrates, esters of (L)-leucine and (L)-alanine generate (D)-carbohydrates, offering the potential to account for the prebiotic link between natural (L)-amino acids and natural (D)-sugars.

Diarylnitroxide diradicals: low-temperature oxidation of diarylamines to nitroxides.

A low temperature method, in which the progress of the oxidation of secondary diarylamines with DMDO at low temperatures is monitored by magnetic resonance spectroscopy (EPR and NMR) and magnetic studies by a Superconducting Quantum Interference Device (SQUID), is developed for preparation of the first m-phenylene based diarylnitroxide diradical. EPR spectroscopy and magnetic studies (SQUID) indicate that the diradical in the dichloromethane matrix predominantly adopts anticonformation ( 2A-anti) and possesses triplet ground state. Similar oxidation experiments for conformationally constrained aza[1 4]metacyclophane provide evidence for the formation of small amounts of the corresponding diarylnitroxide diradical. Both diarylnitroxide diradicals could only be detected at low temperatures (-80 degrees C and below).

Synthesis, structure, and conformation of aza[1n]metacyclophanes.

N-Benzyl substituted aza[1n]metacyclophanes (n = 4, 6, 8, and 10) were prepared in overall 40% isolated yields via Pd-catalyzed aminations. Analyses of the reaction mixtures showed that aza[14]metacyclophane and the related polymer were the primary products ( approximately 60% overall yield); aza[1n]metacyclophanes up to n = 14 and linear oligomers with up to 20 nitrogen atoms (with at least three types of end groups) were detected. Macrocyclic structures for n = 4, 6, and 10 were confirmed by X-ray crystallography. 1,3-Alternate (D(2d)) and 1,3,5-alternate (S(6)) conformations in solution on NMR time scale at low temperatures were found for macrocycles with n = 4 and n = 6, respectively; the barrier for ring inversion was considerably lower for the larger macrocycle.

Stable hydrocarbon diradical, an analogue of trimethylenemethane.

Hydrocarbon diradical 1, a new stable, 3-fold symmetric analogue of trimethylenemethane (TMM) with no heteroatom perturbation, is prepared and studied. Such diradicals should provide new building blocks for high-spin hydrocarbon polyradicals with very strong net ferromagnetic coupling. Magnetic studies (SQUID) and EPR spectroscopy indicate that 1 in tetrahydrofuran-d8 (THF-d8) possesses a triplet (S = 1) ground state, with strong ferromagnetic coupling. After annealing at room temperature, the EPR spectra of 1 (approximately 0.02 M in frozen THF-d8) consist of a single narrow resonance (deltaH(pp) < 1 G), and intermolecular antiferromagnetic coupling is increased by 1 order of magnitude. This behavior is consistent with the presence of exchange narrowing, thus suggesting aggregation of 1 in THF-d8. Blue solutions of 1 in THF-d8 possess a strong UV-vis absorption band at lambda(max) approximately 640 nm. Diradical 1 in THF-d8 is stable (or persistent) at room temperature, with no detectable decomposition for at least 2 days.