Damage control operations in non-trauma patients: Defining criteria for the staged rapid source control laparotomy in emergency general surgery

Background: The staged laparotomy in the operative management of emergency general surgery (EGS) patients is an extension of trauma surgeons operating on this population. Indications for its application, however, are not well defined, and are currently based on the lethal triad used in physiologically-decompensated trauma patients. This study sought to determine the acute indications for the staged, rapid source control laparotomy (RSCL) in EGS patients. Methods: All EGS patients undergoing emergent staged RSCL and non-RSCL over 3years were studied. Demographics, physiologic parameters, perioperative variables, outcomes, and survival were compared. Logistic regression models determined the influence of physiologic parameters on mortality and postoperative complications. EGS-RSCL indications were defined. Results: 215 EGS patients underwent emergent laparotomy; 53 (25%) were staged RSCL. In the 53 patients who underwent a staged RSCL based on the lethal triad, adjusted multivariable regression analysis shows that when used alone, no component of the lethal triad independently improved survival. Staged RSCL may decrease mortality in patients with preoperative severe sepsis / septic shock, and an elevated lactate (≥3); acidosis (pH ≤ 7.25); elderly (≥70); male gender; and multiple comorbidities (≥3). Of the 162 non-RSCL emergent laparotomies, 27 (17%) required unplanned re-explorations; of these, 17 (63%) had sepsis preoperatively and 9 (33%) died. Conclusions: The acute physiologic indicators that help guide operative decisions in trauma may not confer a similar survival advantage in EGS. To replace the lethal triad, criteria for application of the staged RSCL in EGS need to be defined. Based on these results, the indications should include severe sepsis / septic shock, lactate, acidosis, gender, age, and pre-existing comorbidities. When correctly applied, the staged RSCL may help to improve survival in decompensated EGS patients

Novel variants in the PRDX6 Gene and the risk of Acute Lung Injury following major trauma

<p>Abstract</p> <p>Background</p> <p>Peroxiredoxin 6 (<it>PRDX6</it>) is involved in redox regulation of the cell and is thought to be protective against oxidant injury. Little is known about genetic variation within the PRDX6 gene and its association with acute lung injury (ALI). In this study we sequenced the <it>PRDX6 </it>gene to uncover common variants, and tested association with ALI following major trauma.</p> <p>Methods</p> <p>To examine the extent of variation in the <it>PRDX6 </it>gene, we performed direct sequencing of the 5' UTR, exons, introns and the 3' UTR in 25 African American cases and controls and 23 European American cases and controls (selected from a cohort study of major trauma), which uncovered 80 SNPs. <it>In silico </it>modeling was performed using Patrocles and Transcriptional Element Search System (TESS). Thirty seven novel and tagging SNPs were tested for association with ALI compared with ICU at-risk controls who did not develop ALI in a cohort study of 259 African American and 254 European American subjects that had been admitted to the ICU with major trauma.</p> <p>Results</p> <p>Resequencing of critically ill subjects demonstrated 43 novel SNPs not previously reported. Coding regions demonstrated no detectable variation, indicating conservation of the protein. Block haplotype analyses reveal that recombination rates within the gene seem low in both Caucasians and African Americans. Several novel SNPs appeared to have the potential for functional consequence using <it>in silico </it>modeling. Chi²analysis of ALI incidence and genotype showed no significant association between the SNPs in this study and ALI. Haplotype analysis did not reveal any association beyond single SNP analyses.</p> <p>Conclusions</p> <p>This study revealed novel SNPs within the <it>PRDX6 </it>gene and its 5' and 3' flanking regions via direct sequencing. There was no association found between these SNPs and ALI, possibly due to a low sample size, which was limited to detection of relative risks of 1.93 and above. Future studies may focus on the role of <it>PRDX6 </it>genetic variation in other diseases, where oxidative stress is suspected.</p

Food Supply and Seawater pCO2 Impact Calcification and Internal Shell Dissolution in the Blue Mussel Mytilus edulis

Progressive ocean acidification due to anthropogenic CO2 emissions will alter marine ecosytem processes. Calcifying organisms might be particularly vulnerable to these alterations in the speciation of the marine carbonate system. While previous research efforts have mainly focused on external dissolution of shells in seawater under saturated with respect to calcium carbonate, the internal shell interface might be more vulnerable to acidification. In the case of the blue mussel Mytilus edulis, high body fluid pCO2 causes low pH and low carbonate concentrations in the extrapallial fluid, which is in direct contact with the inner shell surface. In order to test whether elevated seawater pCO2 impacts calcification and inner shell surface integrity we exposed Baltic M. edulis to four different seawater pCO2 (39, 142, 240, 405 Pa) and two food algae (310–350 cells mL−1 vs. 1600–2000 cells mL−1) concentrations for a period of seven weeks during winter (5°C). We found that low food algae concentrations and high pCO2 values each significantly decreased shell length growth. Internal shell surface corrosion of nacreous ( = aragonite) layers was documented via stereomicroscopy and SEM at the two highest pCO2 treatments in the high food group, while it was found in all treatments in the low food group. Both factors, food and pCO2, significantly influenced the magnitude of inner shell surface dissolution. Our findings illustrate for the first time that integrity of inner shell surfaces is tightly coupled to the animals' energy budget under conditions of CO2 stress. It is likely that under food limited conditions, energy is allocated to more vital processes (e.g. somatic mass maintenance) instead of shell conservation. It is evident from our results that mussels exert significant biological control over the structural integrity of their inner shell surfaces

PolyQ Repeat Expansions in ATXN2 Associated with ALS Are CAA Interrupted Repeats

Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressive disease leading to paralysis and death. Recently, intermediate length polyglutamine (polyQ) repeats of 27–33 in ATAXIN-2 (ATXN2), encoding the ATXN2 protein, were found to increase risk for ALS. In ATXN2, polyQ expansions of ≥34, which are pure CAG repeat expansions, cause spinocerebellar ataxia type 2. However, similar length expansions that are interrupted with other codons, can present atypically with parkinsonism, suggesting that configuration of the repeat sequence plays an important role in disease manifestation in ATXN2 polyQ expansion diseases. Here we determined whether the expansions in ATXN2 associated with ALS were pure or interrupted CAG repeats, and defined single nucleotide polymorphisms (SNPs) rs695871 and rs695872 in exon 1 of the gene, to assess haplotype association. We found that the expanded repeat alleles of 40 ALS patients and 9 long-repeat length controls were all interrupted, bearing 1–3 CAA codons within the CAG repeat. 21/21 expanded ALS chromosomes with 3CAA interruptions arose from one haplotype (GT), while 18/19 expanded ALS chromosomes with <3CAA interruptions arose from a different haplotype (CC). Moreover, age of disease onset was significantly earlier in patients bearing 3 interruptions vs fewer, and was distinct between haplotypes. These results indicate that CAG repeat expansions in ATXN2 associated with ALS are uniformly interrupted repeats and that the nature of the repeat sequence and haplotype, as well as length of polyQ repeat, may play a role in the neurological effect conferred by expansions in ATXN2

Lung epithelium as a sentinel and effector system in pneumonia – molecular mechanisms of pathogen recognition and signal transduction

Pneumonia, a common disease caused by a great diversity of infectious agents is responsible for enormous morbidity and mortality worldwide. The bronchial and lung epithelium comprises a large surface between host and environment and is attacked as a primary target during lung infection. Besides acting as a mechanical barrier, recent evidence suggests that the lung epithelium functions as an important sentinel system against pathogens. Equipped with transmembranous and cytosolic pathogen-sensing pattern recognition receptors the epithelium detects invading pathogens. A complex signalling results in epithelial cell activation, which essentially participates in initiation and orchestration of the subsequent innate and adaptive immune response. In this review we summarize recent progress in research focussing on molecular mechanisms of pathogen detection, host cell signal transduction, and subsequent activation of lung epithelial cells by pathogens and their virulence factors and point to open questions. The analysis of lung epithelial function in the host response in pneumonia may pave the way to the development of innovative highly needed therapeutics in pneumonia in addition to antibiotics