Targeted temperature management after intraoperative cardiac arrest: a multicenter retrospective study

Purpose

Few outcome data are available about temperature management after intraoperative cardiac arrest (IOCA). We describe targeted temperature management (TTM) (32–34 °C) modalities, adverse events, and association with 1-year functional outcome in patients with IOCA.

Methods

Patients admitted to 11 ICUs after IOCA in 2008–2013 were studied retrospectively. The main outcome measure was 1-year functional outcome.

Results

Of the 101 patients [35 women and 66 men; median age, 62 years (interquartile range, 42–72)], 68 (67.3%) were ASA PS I to III and 57 (56.4%) had emergent surgery. First recorded rhythms were asystole in 44 (43.6%) patients, pulseless electrical activity in 36 (35.6%), and ventricular fibrillation/tachycardia in 20 (19.8%). Median times from collapse to cardiopulmonary resuscitation and return of spontaneous circulation (ROSC) were 0 min (0–0) and 10 min (4–20), respectively. The 30 (29.7%) patients who received TTM had an increased risk of infection (P = 0.005) but not of arrhythmia, bleeding, or metabolic/electrolyte disorders. By multivariate analysis, one or more defibrillation before ROSC was positively associated with a favorable functional outcome at 1-year (OR 3.06, 95% CI 1.05–8.95, P = 0.04) and emergency surgery was negatively associated with 1-year favorable functional outcome (OR 0.36; 95% CI 0.14–0.95, P = 0.038). TTM use was not independently associated with 1-year favorable outcome (OR 0.82; 95% CI 0.27–2.46, P = 0.72).

Conclusions

TTM was used in less than one-third of patients after IOCA. TTM was associated with infection but not with bleeding or coronary events in this setting. TTM did not independently predict 1-year favorable functional outcome after IOCA in this study.

     

P2X2 and P2X5 subunits define a new heteromeric receptor with P2X7-like properties

Ligand-gated ion channels are prototypic oligomeric membrane proteins whose stoichiometry determines their functional properties and subcellular localization. Deciphering the quaternary structure of such protein complexes is an arduous task and usually requires the combination of multiple approaches. ATP-gated P2X receptors are formed by the association of three subunits, but the quaternary arrangement of the seven P2X subunits at the plasma membrane remains poorly characterized. By combining bioluminescence resonance energy transfer, bifunctional fluorescence complementation and protein biochemistry, we developed an experimental approach that allows precise determination of rat P2X receptor quaternary assembly. We found that P2X5 subunits associate with P2X1, P2X2, and P2X4 subunits. We demonstrate that P2X5 and P2X2 subunits interact to form as yet uncharacterized heteromeric receptors with alternate stoichiometries, both present at the plasma membrane. P2X2/5 receptors display functional properties such as pore dilatation, membrane blebbing, and phosphatidylserine exposure that were previously thought to be characteristic hallmarks of the P2X7 receptor. In mouse, P2X2 and P2X5 subunits colocalize and physically interact in specific neuronal populations suggesting that other P2X receptors might contribute to cellular responses typically attributed to P2X7 receptor.     

Plague in Guinea pigs and its prevention by subunit vaccines

Human pneumonic plague is a devastating and transmissible disease for which a Food and Drug Administration-approved vaccine is not available. Suitable animal models may be adopted as a surrogate for human plague to fulfill regulatory requirements for vaccine efficacy testing. To develop an alternative to pneumonic plague in nonhuman primates, we explored guinea pigs as a model system. On intranasal instillation of a fully virulent strain, Yersinia pestis CO92, guinea pigs developed lethal lung infections with hemorrhagic necrosis, massive bacterial replication in the respiratory system, and blood-borne dissemination to other organ systems. Expression of the Y. pestis F1 capsule was not required for the development of pulmonary infection; however, the capsule seemed to be important for the establishment of bubonic plague. The mean lethal dose (MLD) for pneumonic plague in guinea pigs was estimated to be 1000 colony-forming units. Immunization of guinea pigs with the recombinant forms of LcrV, a protein that resides at the tip of Yersinia type III secretion needles, or F1 capsule generated robust humoral immune responses. Whereas LcrV immunization resulted in partial protection against pneumonic plague challenge with 250 MLD Y. pestis CO92, immunization with recombinant F1 did not. rV10, a vaccine variant lacking LcrV residues 271-300, elicited protection against pneumonic plague, which seemed to be based on conformational antibodies directed against LcrV.     

Tropomyosin-4 correlates with higher SBR grades and tubular differentiation in infiltrating ductal breast carcinomas: an immunohistochemical and proteomics-based study

The aim of this study is to evaluate tropomyosin-4 (TM4) expression in infiltrating ductal breast carcinomas (IDCAs), as well as its prognostic significance. Using a 2-DE/MALDI-TOF mass spectrometry investigation coupled with an immunohistochemical approach, we have assessed the expression of TM4 in IDCAs, as well as in other types of breast tumors. Proteomic analyses revealed an increased expression of tropomyosin-4 in IDCA tumors. Using immunohistochemistry, overexpression of tropomyosin-4 was confirmed in 51 additional tumor specimens. Statistical analyses revealed, however, no significant correlations between tropomyosin-4 expression and clinicopathological parameters of the disease including tumor stage, patient age, estrogen and progesterone receptor status, and lymph node metastasis occurrence. A significant association was found, however, with a high Scarf–Bloom–Richardson (SBR) grade, a known marker of tumor severity. Additionally, the SBR component showing a correlation with TM4 expression was the tubular differentiation status. This study demonstrates the upregulation of tropomyosin-4 in IDCA tissues, which may highlight its involvement in breast cancer development. Our findings also support a link between tropomyosin-4 expression and aggressiveness of IDCA tumors.     

Therapeutic drug monitoring of clomipramine and amitriptyline in a depressed patient with upper digestive tract resection

We describe a 55-year-old woman with extensive digestive resection and recurrent depressive disorder resistant to oral clomipramine tablets but not to an oral solution of amitriptyline. In the light of this case report, the potential mechanisms of drug resistance after digestive resection are discussed, including the importance of drug monitoring.     

New insights into immune mechanisms of antiperlecan/LG3 antibody production: Importance of T cells and innate B1 cells

Autoantibodies against perlecan/LG3 (anti‐LG3) have been associated with increased risks of delayed graft function, acute rejection, and reduced long‐term survival. High titers of anti‐LG3 antibodies have been found in de novo renal transplants recipients in the absence of allosensitizing or autoimmune conditions. Here, we seek to understand the pathways controlling anti‐LG3 production prior to transplantation. Mice immunized with recombinant LG3 produce concomitantly IgM and IgG anti‐LG3 antibodies suggesting a memory response. ELISpot confirmed the presence of LG3‐specific memory B cells in nonimmunized mice. Purification of B1 and B2 subtypes identified peritoneal B1 cells as the major source of memory B cells reactive to LG3. Although nonimmunized CD4‐deficient mice were found to express LG3‐specific memory B cells, depletion of CD4⁺ T cells in wild type mice during immunization significantly decreased anti‐LG3 production. These results demonstrate that B cell memory to LG3 is T cell independent but that production of anti‐LG3 antibodies requires T cell help. Further supporting an important role for T cells in controlling anti‐LG3 levels, we found that human renal transplant recipients show a significant decrease in anti‐LG3 titers upon the initiation of CNI‐based immunosuppression. Collectively, these results identify T cell targeting interventions as a means of reducing anti‐LG3 levels in renal transplant patients.