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The evolution of hypermutators in response to antibiotic treatment in both clinical and laboratory settings provides a unique context for the study of adaptive evolution. With increased mutation rates, the number of hitchhiker mutations within an evolving hypermutator population is remarkably high and presents substantial challenges in determining which mutations are adaptive. Intriguingly however, hypermutators also provide an opportunity to explore deeply the accessible evolutionary trajectories that lead to increased organism fitness, in this case the evolution of antibiotic resistance to the clinically relevant antibiotic tigecycline by the hospital pathogen Acinetobacter baumannii. Using a continuous culture system, AB210M, a clinically derived strain of A. baumannii, was evolved to tigecycline resistance. Analysis of the adapted populations showed that nearly all the successful lineages became hypermutators via movement of a mobile element to inactivate mutS. In addition, metagenomic analysis of population samples revealed another 896 mutations that occurred at a frequency greater than 5% in the population, while 38 phenotypically distinct individual colonies harbored a total of 1712 mutations. These mutations were scattered throughout the genome and affected ~40% of the coding sequences. The most highly mutated gene was adeS, a known tigecycline-resistance gene; however, adeS was not solely responsible for the high level of TGC resistance. Sixteen other genes stood out as potentially relevant to increased resistance. The five most prominent candidate genes (adeS, rpsJ, rrf, msbA, and gna) consistently re-emerged in subsequent replicate population studies suggesting they are likely to play a role in adaptation to tigecycline. Interestingly, the repeated evolution of a hypermutator phenotype in response to antibiotic stress illustrates not only a highly adaptive strategy to resistance, but also a remarkably efficient survey of successful evolutionary trajectories.

Hypercholesterolemia, the driving force of atherosclerosis, accelerates the expansion and mobilization of hematopoietic stem and progenitor cells (HSPCs). The molecular determinants connecting hypercholesterolemia with hematopoiesis are unclear. Here, we report that a somite-derived prohematopoietic cue, AIBP, orchestrates HSPC emergence from the hemogenic endothelium, a type of specialized endothelium manifesting hematopoietic potential. Mechanistically, AIBP-mediated cholesterol efflux activates endothelial Srebp2, the master transcription factor for cholesterol biosynthesis, which in turn transactivates Notch and promotes HSPC emergence. Srebp2 inhibition impairs hypercholesterolemia-induced HSPC expansion. Srebp2 activation and Notch up-regulation are associated with HSPC expansion in hypercholesterolemic human subjects. Genome-wide chromatin immunoprecipitation followed by sequencing (ChIP-seq), RNA sequencing (RNA-seq), and assay for transposase-accessible chromatin using sequencing (ATAC-seq) indicate that Srebp2 transregulates Notch pathway genes required for hematopoiesis. Our studies outline an AIBP-regulated Srebp2-dependent paradigm for HSPC emergence in development and HPSC expansion in atherosclerotic cardiovascular disease.

Damage control (DC) packing is used selectively in patients in shock with extensive abdominal, thoracic, perineal/genital/perirectal, neck/axillae/groin (junctional), and extremity injury to stop bleeding. In multiple casualty scenarios, DC packing may be used to facilitate an abbreviated surgery and thus “buy time”. The packing is by guideline or military doctrine removed or exchanged 1–3 days later in a planned reoperation. In remote environments, however, where timely evacuation cannot occur and resources are limited, it may be necessary for packing to be left in place longer than 3 days. Also, in Large Scale Combat Operations, Multi-Domain Operations, and Distributed Maritime Operations, evacuation will be accomplished by nonsurgeons and may last several days. Prolonged retention of packing is associated with complications, but significant rebleeding may occur upon removal. This article reviews the benefits and hazards of DC packing removal to inform decision making by both surgeons and nonsurgeons. We conclude that except for Dismounted Complex Blast Injury most DC gauze packing does not mandatorily need to be removed or exchanged within a three-day window. •Most damage control gauze packing does not mandatorily need to be removed or exchanged in a 3 day window.•Risks of prolonged packing include invasive infection, abscess, empyema, and enteric fistula.•Infrequent dressing changes following a thorough initial debridement may be an expedient austere extremity wound strategy.•Consumption of limited resources and risk of rebleeding must be weighed prior to packing removal.

Nurses across clinical settings routinely navigate high patient loads, emotionally charged environments, and institutional pressures, all of which contribute to elevated levels of stress and burnout. Shinrin-yoku (forest bathing) is one method for combating negative effects of stress. This practice of natural immersion has been shown to decrease cortisol and adrenaline values while increasing positive hormonal and cell-mediated agents. Integrating nature-based interventions can provide accessible ways to reduce nurse burnout and strengthen workforce resilience.

Venous thromboembolism (VTE) remains a serious complication after traumatic brain injury (TBI). This study examined the incidence and risk factors for VTE despite early, protocolized chemoprophylaxis (CP) with anti-Xa–based escalation. Retrospective cohort of adult polytrauma patients with TBI (9/16–12/21). Patients developing clinically significant deep vein thrombosis (DVT) or pulmonary embolism (PE) were compared to those without. Multivariable frequentist and Bayesian regression identified predictors of VTE. Of 1554 patients, 54 (3.5 ​%) developed VTE (DVT 1.5 ​%, PE 1.5 ​%, both 0.5 ​%). Patients with VTE had higher injury severity (ISS 34 vs 27), lower GCS (3 vs 12), and greater base deficit. Mean time to prophylaxis was similar (56 vs 44 ​h). Heparin CP, enoxaparin dose escalation, and increased base deficit independently predicted VTE. Despite early CP, VTE occurred in 3.5 ​% of patients. Enoxaparin remains standard; future efforts should minimize sub-prophylactic anti-Xa levels. Level III, prognostic/epidemiological. •3.5 ​% of severe TBI polytrauma patients developed VTE despite early prophylaxis.•Heparin prophylaxis was associated with increased odds of VTE.•Enoxaparin dose escalation independently predicted VTE development.•Greater admission base deficit was linked to VTE risk.

Patients with occult pneumothorax (OPTX) requiring positive-pressure ventilation (PPV) face uncertain risks of tension pneumothorax or chest drainage complications. Adults with traumatic OPTXs requiring PPV were randomized to drainage/observation, with the primary outcome of composite “respiratory distress” (RD)). Seventy-five (75) patients were randomized to observation, 67 to drainage. RD occurred in 38% observed and 25% drained (p = 0.14; Power = 0.38), with no mortality differences. One-quarter of observed patients failed, reaching 40% when ventilated >5 days. Twenty-three percent randomized to drainage had complications or ineffectual drains. RD was not significantly different with observation. Thus, OPTXs may be cautiously observed in stable patients undergoing short-term PPV when prompt “rescue drainage” is immediately available. As 40% of patients undergoing prolonged (≥5 days) ventilation (PPPV) require drainage, we suggest consideration of chest drainage performed with expert guidance to reduce risk of chest tube complications. Therapeutic study, level II. •The composite primary endpoint of Respiratory Distress was not significantly different in either treatment group.•One-quarter of those allocated to observation failed and required drainage.•Nearly 40% of those ventilated for more than 5 days required pleural drainage.•Six percent of those being observed underwent an urgent pleural drainage.

Traumatic inuries to the pancreas are notoriously challenging to diagnose and treat. Detecting a main pancreatic ductal injury can be particularly difficult on screening computed tomography (CT). Twenty-four blinded faculty clinicians from 4 differing specialties and 6 institutions reviewed 9 video CT cases of potential pancreatic ductal injuries. Clinician performance in detection of confirmed grade III pancreatic injuries varied widely among specialties. This heterogeneity confirms the critical need for multidisciplinary care and image interpretation for even “minor” (i.e., not grade IV or V) potential pancreatic injuries to optimize outcomes for injured patients. The ubiquitous availability of electronic devices allows real-time collegial second opinions to be easily available.

ObjectivesPatients with traumatic intracranial hemorrhage (ICH) often undergo early stability CT scans to evaluate for progression of bleeding. The factors associated with progression after initiating venous thromboembolism (VTE) chemoprophylaxis (CP) remain poorly described. This study aimed to determine the rate of and factors associated with ICH progression following CP initiation.MethodsThis retrospective observational study included adult (≥16 years) polytrauma patients with blunt or penetrating traumatic brain injury (TBI) admitted between September 2016 and December 2021. Progression was defined as a radiographic increase in ICH following VTE CP initiation, determined by neurosurgery or radiology faculty. Postprophylaxis CT scans were obtained based on clinical deterioration. Associated factors, neurosurgical intervention rates, and outcomes were evaluated.ResultsAmong 1390 included patients, ICH progression occurred in 3% (43) following CP initiation. Patients with progression were older (55 vs 45 years) and had higher injury severity scores (33 vs 27; p<0.05). Rates of pneumonia (49% vs 21%) and sepsis (19% vs 9%) were higher in the progression group (p<0.05). There was no difference between groups in time to prophylaxis initiation (40 vs 38 hours), survival (88% vs 92%), or VTE incidence (0% vs 4%; all p=NS). Factors associated with progression included midline shift (21% vs 6%), subdural hematoma (47% vs 26%), and prior progression on 6-hour stability CT (64% vs 34%; p<0.05). Multivariate analysis confirmed these findings. Among progression patients, 9% required intervention after CP, with only two requiring craniotomy.ConclusionsICH progression is rare (3%) after VTE CP initiation. Associated factors align with spontaneous progression, suggesting that ICH progression is independent of early VTE prophylaxis (<48 hours). These findings support the safety of early VTE CP as the standard of care for mitigating VTE risk in TBI patients with TBI.Level of evidenceLevel III, retrospective study with up to two negative criteria.

The Pringle manoeuvre (vascular inflow occlusion) has been a mainstay technique in trauma surgery and hepato-pancreato-biliary surgery since it was first described in the early 1900s. We sought to determine how frequently the manoeuvre is used today for both elective and emergent cases in these disciplines. To reflect on its evolution, we evaluated the Pringle manoeuvre over a recent 10-year period (2010–2020). We found it is used less frequently owing to more frequent nonoperative management and more advanced elective hepatic resection techniques. Continuing educational collaboration is critical to ensure continued insight into the impact of hepatic vascular inflow occlusion among trainees who observe this procedure less frequently.