Prospective observational pilot study of the T2Resistance panel in the T2Dx system for detection of resistance genes in bacterial bloodstream infections.

Early initiation of antimicrobial therapy targeting resistant bacterial pathogens causing sepsis and bloodstream infections (BSIs) is critical for a successful outcome. The T2Resistance Panel (T2R) detects the following resistance genes within organisms that commonly cause BSIs directly from patient blood samples: blaKPC, blaCTXM-14/15, blaNDM/bla/IMP/blaVIM, blaAmpC, blaOXA, vanA, vanB, and mecA/mecC. We conducted a prospective study in two major medical centers for the detection of circulating resistance genes by T2R in patients with BSIs. T2R reports were compared to antimicrobial susceptibility testing (AST), phenotypic identification, and standard molecular detection assays. Among 59 enrolled patients, 25 resistance genes were identified: blaKPC (n = 10), blaNDM/bla/IMP/blaVIM (n = 5), blaCTXM-14/15 (n = 4), blaAmpC (n = 2), and mecA/mecC (n = 4). Median time-to-positive-T2R in both hospitals was 4.4 hours [interquartile range (IQR): 3.65-4.97 hours] in comparison to that for positive blood cultures with final reporting of AST of 58.34 h (IQR: 45.51-111.2 hours; P < 0.0001). The sensitivity of T2R to detect the following genes in comparison to AST was 100% for blaCTXM-14/15, blaNDM/bla/IMP/blaVIM, blaAmpC, mecA/mecC and 87.5% for blaKPC. When monitored for the impact of significant antimicrobial changes, there were 32 events of discontinuation of unnecessary antibiotics and 17 events of escalation of antibiotics, including initiation of ceftazidime/avibactam in six patients in response to positive T2R results for blaKPC. In summary, T2R markers were highly sensitive for the detection of drug resistance genes in patients with bacterial BSIs, when compared with standard molecular resistance detection systems and phenotypic identification assays while significantly reducing by approximately 90% the time to detection of resistance compared to standard methodology and impacting clinical decisions for antimicrobial therapy. IMPORTANCE: This is the first reported study to our knowledge to identify key bacterial resistance genes directly from the bloodstream within 3 to 5 hours in patients with bloodstream infections and sepsis. The study further demonstrated a direct effect in modifying initial empirical antibacterial therapy in response to T2R signal to treat resistant bacteria causing bloodstream infections and sepsis.

Effect of Different Early Oxygenation Levels on Clinical Outcomes of Patients Presenting in the Emergency Department With Severe Traumatic Brain Injury.

STUDY OBJECTIVE: Despite the almost universal administration of supplemental oxygen in patients presenting in the emergency department (ED) with severe traumatic brain injury, optimal early oxygenation levels are unknown. Therefore, we aimed to examine the effect of different early oxygenation levels on the clinical outcomes of patients presenting in the emergency department with severe traumatic brain injury. METHODS: We performed a secondary analysis of the Resuscitation Outcomes Consortium Traumatic Brain Injury Hypertonic Saline randomized controlled trial by including patients with Glasgow Coma Scale ≤8. Early oxygenation levels were assessed by the worst value of arterial partial pressure of oxygen (PaO2) during the first 4 hours of presentation in the emergency department. The primary outcome was 6-month neurologic status, as assessed by the Extended Glasgow Outcome Scale. A binary logistic regression was utilized, and an odds ratio (OR) with 95% (95% confidence intervals) was calculated. RESULTS: A total of 910 patients were included. In unadjusted (crude) analysis, a PaO2 of 101 to 250 mmHg (OR, 0.59 [0.38 to 0.91]), or 251 to 400 mmHg (OR, 0.53 [0.34 to 0.83]) or ≥401 mmHg (OR, 0.31 [0.20 to 0.49]) was less likely to be associated with poor neurologic status when compared with a PaO2 of ≤100 mmHg. This was also the case for adjusted analyses (including age, pupillary reactivity, and Revised Trauma Score). CONCLUSION: High oxygenation levels as early as the first 4 hours of presentation in the emergency department may not be adversely associated with the long-term neurologic status of patients with severe traumatic brain injury. Therefore, during the early phase of trauma, clinicians may focus on stabilizing patients while giving low priority to the titration of oxygenation levels.

Endotheliopathy in Acute COVID-19 and Long COVID.

The pulmonary endothelium is a highly regulated organ that performs a wide range of functions under physiological and pathological conditions. Since endothelial dysfunction has been demonstrated to play a direct role in sepsis and acute respiratory distress syndrome, its role in COVID-19 has also been extensively investigated. Indeed, apart from the COVID-19-associated coagulopathy biomarkers, new biomarkers were recognised early during the pandemic, including markers of endothelial cell activation or injury. We systematically searched the literature up to 10 March 2023 for studies examining the association between acute and long COVID-19 severity and outcomes and endothelial biomarkers.

Neuromonitoring in Severe Traumatic Brain Injury: A Bibliometric Analysis.

Traumatic brain injury (TBI) is the leading cause of mortality and disability among trauma-related injuries. Neuromonitoring plays an essential role in the management and prognosis of patients with severe TBI. Our bibliometric study aimed to identify the knowledge base, define the research front, and outline the social networks on neuromonitoring in severe TBI. We conducted an electronic search for articles related to neuromonitoring in severe TBI in Scopus. A descriptive analysis retrieved evidence on the most productive authors and countries, the most cited articles, the most frequently publishing journals, and the most common author's keywords. Through a three-step network extraction process, we performed a collaboration analysis among universities and countries, a cocitation analysis, and a word cooccurrence analysis. A total of 1884 records formed the basis of our bibliometric study. We recorded an increasing scientific interest in the use of neuromonitoring in severe TBI. Czosnyka, Hutchinson, Menon, Smielewski, and Stocchetti were the most productive authors. The most cited document was a review study by Maas et al. There was an extensive collaboration among universities. The most common keywords were "intracranial pressure," with an increasing interest in magnetic resonance imaging and cerebral perfusion pressure monitoring. Neuromonitoring constitutes an area of active research. The present findings indicate that intracranial pressure monitoring plays a pivotal role in the management of severe TBI. Scientific interest shifts to magnetic resonance imaging and individualized patient care on the basis of optimal cerebral perfusion pressure.

Exposure to Stress-Dose Steroids and Lethal Septic Shock After In-Hospital Cardiac Arrest: Individual Patient Data Reanalysis of Two Prior Randomized Clinical Trials that Evaluated the Vasopressin-Steroids-Epinephrine Combination Versus Epinephrine Alone.

PURPOSE: Low-dose steroids may reduce the mortality of severely ill patients with septic shock. We sought to determine whether exposure to stress-dose steroids during and/or after cardiopulmonary resuscitation is associated with reduced risk of death due to postresuscitation septic shock. METHODS: We analyzed pooled, individual patient data from two prior, randomized clinical trials (RCTs). RCTs evaluated vasopressin, steroids, and epinephrine (VSE) during resuscitation and stress-dose steroids after resuscitation in vasopressor-requiring, in-hospital cardiac arrest. In the second RCT, 15 control group patients received open-label, stress-dose steroids. Patients with postresuscitation shock were assigned to a Steroids (n = 118) or No Steroids (n = 73) group according to an "as-treated" principle. We used cumulative incidence competing risks Cox regression to determine cause-specific hazard ratios (CSHRs) for pre-specified predictors of lethal septic shock (primary outcome). In sensitivity analyses, data were analyzed according to the intention-to-treat (ITT) principle (VSE group, n = 103; control group, n = 88). RESULTS: Lethal septic shock was less likely in Steroids versus No Steroids group, CSHR, 0.40, 95% confidence interval (CI), 0.20-0.82; p = 0.012. ITT analysis yielded similar results: VSE versus Control, CSHR, 0.44, 95% CI, 0.23-0.87; p = 0.019. Adjustment for significant, between-group baseline differences in composite cardiac arrest causes such as "hypotension and/or myocardial ischemia" did not appreciably affect the aforementioned CSHRs. CONCLUSIONS: In this reanalysis, exposure to stress-dose steroids (primarily in the context of a combined VSE intervention) was associated with lower risk of postresuscitation lethal septic shock.

Publisher Correction: Exposure to Stress-Dose Steroids and Lethal Septic Shock After In-Hospital Cardiac Arrest: Individual Patient Data Reanalysis of Two Prior Randomized Clinical Trials that Evaluated the Vasopressin-Steroids-Epinephrine Combination Versus Epinephrine Alone.

The original version of this article unfortunately contained a mistake. In Table 2, the frequency of Septic Shock reported just below the frequency of "At least 1 Episode of VAP" actually corresponds to the First (and not the Second) Episode of VAP during the postresuscitation period.

Severe Traumatic Brain Injury and Pulmonary Embolism: Risks, Prevention, Diagnosis and Management.

Severe traumatic brain injury (sTBI) is a silent epidemic, causing approximately 300,000 intensive care unit (ICU) admissions annually, with a 30% mortality rate. Despite worldwide efforts to optimize the management of patients and improve outcomes, the level of evidence for the treatment of these patients remains low. The concomitant occurrence of thromboembolic events, particularly pulmonary embolism (PE), remains a challenge for intensivists due to the risks of anticoagulation to the injured brain. We performed a literature review on sTBI and concomitant PE to identify and report the most recent advances on this topic. We searched PubMed and Scopus for papers published in the last five years that included the terms "pulmonary embolism" and "traumatic brain injury" in their title or abstract. Exclusion criteria were papers referring to children, non-sTBI populations, and post-acute care. Our search revealed 75 papers, of which 38 are included in this review. The main topics covered include the prevalence of and risk factors for pulmonary embolism, the challenges of timely diagnosis in the ICU, the timing of pharmacological prophylaxis, and the treatment of diagnosed PE.

The Role of Automated Infrared Pupillometry in Traumatic Brain Injury: A Narrative Review.

Pupillometry, an integral component of neurological examination, serves to evaluate both pupil size and reactivity. The conventional manual assessment exhibits inherent limitations, thereby necessitating the development of portable automated infrared pupillometers (PAIPs). Leveraging infrared technology, these devices provide an objective assessment, proving valuable in the context of brain injury for the detection of neuro-worsening and the facilitation of patient monitoring. In cases of mild brain trauma particularly, traditional methods face constraints. Conversely, in severe brain trauma scenarios, PAIPs contribute to neuro-prognostication and non-invasive neuromonitoring. Parameters derived from PAIPs exhibit correlations with changes in intracranial pressure. It is important to acknowledge, however, that PAIPs cannot replace invasive intracranial pressure monitoring while their widespread adoption awaits robust support from clinical studies. Ongoing research endeavors delve into the role of PAIPs in managing critical neuro-worsening in brain trauma patients, underscoring the non-invasive monitoring advantages while emphasizing the imperative for further clinical validation. Future advancements in this domain encompass sophisticated pupillary assessment tools and the integration of smartphone applications, emblematic of a continually evolving landscape.