A Comparison of Cooling Techniques to Treat Cardiac Arrest Patients with Hypothermia

Introduction. We sought to compare the performance of endovascular cooling to conventional surface cooling after cardiac arrest. Methods. Patients in coma following cardiopulmonary resuscitation were cooled with an endovascular cooling catheter or with ice bags and cold-water-circulating cooling blankets to a target temperature of 32.0–34.0°C for 24 hours. Performance of cooling techniques was compared by (1) number of hourly recordings in target temperature range, (2) time elapsed from the written order to initiate cooling and target temperature, and (3) adverse events during the first week. Results. Median time in target temperature range was 19 hours (interquartile range (IQR), 16–20) in the endovascular group versus. 10 hours (IQR, 7–15) in the surface group (P = .001). Median time to target temperature was 4 (IQR, 2.8–6.2) and 4.5 (IQR, 3–6.5) hours, respectively (P = .67). Adverse events were similar. Conclusion. Endovascular cooling maintains target temperatures better than conventional surface cooling

Use of Thromboelastography in the Evaluation and Management of Patients With Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Traumatic brain injury is associated with coagulopathy that increases mortality risk. Viscoelastic hemostatic assays such as thromboelastography (Haemonetics SA, Signy, Switzerland) provide rapid coagulopathy assessment and may be particularly useful for goal-directed treatment of traumatic brain injury patients. We conducted a systematic review to assess thromboelastography in the evaluation and management of coagulopathy in traumatic brain injury patients. Data sources: MEDLINE, PubMed Central, Embase, and CENTRAL. Study selection: Clinical studies of adult patients with traumatic brain injury (isolated or polytrauma) who were assessed by either standard thromboelastography or thromboelastography with platelet mapping plus either conventional coagulation assays or platelet function assays from January 1999 to June 2021. Data extraction: Demographics, injury mechanism and severity, diagnostic, laboratory data, therapies, and outcome data were extracted for analysis and comparison. Data synthesis: Database search revealed 1,169 sources; eight additional articles were identified by the authors. After review, 31 publications were used for qualitative analysis, and of these, 16 were used for quantitative analysis. Qualitative and quantitative analysis found unique patterns of thromboelastography and thromboelastography with platelet mapping parameters in traumatic brain injury patients. Patterns were distinct compared with healthy controls, nontraumatic brain injury trauma patients, and traumatic brain injury subpopulations including those with severe traumatic brain injury or penetrating traumatic brain injury. Abnormal thromboelastography K-time and adenosine diphosphate % inhibition on thromboelastography with platelet mapping are associated with decreased survival after traumatic brain injury. Subgroup meta-analysis of severe traumatic brain injury patients from two randomized controlled trials demonstrated improved survival when using a viscoelastic hemostatic assay-guided resuscitation strategy (odds ratio, 0.39; 95% CI, 0.17-0.91; p = 0.030). Conclusions: Thromboelastography and thromboelastography with platelet mapping characterize coagulopathy patterns in traumatic brain injury patients. Abnormal thromboelastography profiles are associated with poor outcomes. Conversely, treatment protocols designed to normalize abnormal parameters may be associated with improved traumatic brain injury patient outcomes. Current quality of evidence in this population is low; so future efforts should evaluate viscoelastic hemostatic assay-guided hemostatic resuscitation in larger numbers of traumatic brain injury patients with specific focus on those with traumatic brain injury-associated coagulopathy

Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition

Salt-Resistant Alpha-Helical Cationic Antimicrobial Peptides

Analogues based on the insect cecropin–bee melittin hybrid peptide (CEME) were studied and analyzed for activity and salt resistance. The new variants were designed to have an increase in amphipathic α-helical content (CP29 and CP26) and in overall positive charge (CP26). The α-helicity of these peptides was demonstrated by circular dichroism spectroscopy in the presence of liposomes. CP29 was shown to have activity against gram-negative bacteria that was similar to or better than those of the parent peptides, and CP26 had similar activity. CP29 had cytoplasmic membrane permeabilization activity, as assessed by the unmasking of cytoplasmic β-galactosidase, similar to that of CEME and its more positively charged derivative named CEMA, whereas CP26 was substantially less effective. The activity of the peptides was not greatly attenuated by an uncoupler of membrane potential, carbonyl cyanide-m-chlorophenylhydrazone. The tryptophan residue in position 2 was shown to be necessary for interaction with cell membranes, as demonstrated by a complete lack of activity in the peptide CP208. Peptides CP29, CEME, and CEMA were resistant to antagonism by 0.1 to 0.3 M NaCl; however, CP26 was resistant to antagonism only by up to 160 mM NaCl. The peptides were generally more antagonized by 3 and 5 mM Mg(2+) and by the polyanion alginate. It appeared that the positively charged C terminus in CP26 altered its ability to permeabilize the cytoplasmic membrane of Escherichia coli, although CP26 maintained its ability to kill gram-negative bacteria. These peptides are potential candidates for future therapeutic drugs

Immunomodulatory Activities of Small Host Defense Peptides

Recent studies have demonstrated that in addition to their antimicrobial activity, cationic host defense peptides, like the human cathelicidin LL-37, perform many activities relating to innate immunity, including the induction or modulation of chemokine and cytokine production, alteration of gene expression in host cells, and inhibition of proinflammatory responses of host cells to bacterial components such as lipopolysaccharide (LPS) in vitro and in vivo. To investigate if these properties are shared by smaller peptides, two cathelicidin peptides derived from bovine neutrophils, the 13-mer indolicidin and Bac2A, a linear 12-amino-acid derivative of bactenecin, were compared to the 37-amino-acid peptide LL-37. Indolicidin, like LL-37, inhibited LPS-induced tumor necrosis factor alpha (TNF-α) secretion, even when added up to an hour after the addition of Escherichia coli O111:B4 LPS to the human macrophage/monocyte-like THP-1 cell line. In contrast, Bac2A demonstrated no significant antiendotoxin activity. At low concentrations, indolicidin and LL-37 acted synergistically to suppress LPS-induced production of TNF-α. Indolicidin was analogous to LL-37 in its ability to induce the production of the chemokine interleukin-8 (IL-8) in a human bronchial cell line, 16HBE14o(−), but it was unable to induce production of IL-8 in THP-1 cells. In contrast, Bac2A was unable to induce IL-8 in either cell type. Conversely, Bac2A was chemotactic for THP-1 cells at concentrations between 10 and 100 μg/ml, while indolicidin and LL-37 were not chemotactic at these concentrations for THP-1 cells. This indicates that in addition to the potential for direct microbicidal activity, cationic host defense peptides may have diverse and complementary abilities to modulate the innate immune response