Comparative Effectiveness of Intracranial Pressure Monitoring on 6-Month Outcomes of Critically Ill Patients With Traumatic Brain Injury.

Importance: While the relationship between persistent elevations in intracranial pressure (ICP) and poorer outcomes is well established for patients with traumatic brain injury (TBI), there is no consensus on how ICP measurements should drive treatment choices, and the effectiveness of ICP monitoring remains unknown. Objective: To evaluate the effectiveness of ICP monitoring on short- and mid-term outcomes of patients with TBI. Design, Setting, and Participants: CREACTIVE was a prospective cohort study that started in March 2014 and lasted 5 years. More than 8000 patients with TBI were enrolled at 83 intensive care units (ICUs) from 7 countries who joined the CREACTIVE Consortium. Patients with TBI who met the Brain Trauma Foundation guidelines for ICP monitoring were selected for the current analyses, which were performed from January to November 2022. Exposure: Patients who underwent ICP monitoring within 2 days of injury (exposure group) were propensity score-matched to patients who were not monitored or who underwent monitoring 2 days after the injury (control group). Main Outcome and Measure: Functional disability at 6 months as indicated by Glasgow Outcome Scale-Extended (GOS-E) score. Results: A total of 1448 patients from 43 ICUs in Italy and Hungary were eligible for analysis. Of the patients satisfying the ICP-monitoring guidelines, 503 (34.7%) underwent ICP monitoring (median [IQR] age: 45 years [29-61 years]; 392 males [77.9%], 111 females [22.1%]) and 945 were not monitored (median [IQR] age: 66 years [48-78 years]; 656 males [69.4%], 289 females [30.6%]). After matching to balance the variables, worse 6-month recovery was observed for monitored patients compared with nonmonitored patients (death/vegetative state: 39.2% vs 40.6%; severe disability: 33.2% vs 25.4%; moderate disability: 15.7% vs 14.9%; good recovery: 11.9% vs 19.1%, respectively; P = .005). Monitored patients received medical therapies significantly more frequently. Conclusions and Relevance: In this cohort study, ICP monitoring was associated with poorer recovery and more frequent medical interventions with their relevant adverse effects. Optimizing the value of ICP monitoring for TBI requires further investigation on monitoring indications, clinical interventions, and management protocols.

Diagnostic accuracy for hemoperitoneum, influence on prehospital times and time-to-definitive treatment of prehospital FAST: A systematic review and individual participant data meta-analysis.

BACKGROUND: Focused assessment sonography for trauma (FAST) performed in the prehospital setting may improve trauma care by influencing treatment decisions and reducing time to definitive care, but its accuracy and benefits remain uncertain. This systematic review evaluated the diagnostic accuracy of prehospital FAST in detecting hemoperitoneum and its effects on prehospital time and time to definitive diagnosis or treatment. METHODS: We systematically searched PubMed, Embase, and Cochrane library up to November 11th, 2022. Studies investigating prehospital FAST and reporting at least one outcome of interest for this review were considered eligible. The primary outcome was prehospital FAST diagnostic accuracy for hemoperitoneum. A random-effect meta-analysis, including individual patient data, was performed to calculate the pooled outcomes with 95% confidence intervals (CI). Quality of studies was assessed using the QUADAS-2 tool for diagnostic accuracy. RESULTS: We included 21 studies enrolling 5790 patients. The pooled sensitivity and specificity of prehospital FAST for hemoperitoneum were 0.630 (0.454 - 0.777) and 0.970 (0.957-0.979), respectively. Prehospital FAST was performed in a median of 2.72 (2.12 - 3.31) minutes without increasing prehospital times (pooled median difference of 2.44 min [95% CI: -3.93 - 8.81]) compared to standard management. Prehospital FAST findings changed on-scene trauma care in 12-48% of cases, the choice of admitting hospital in 13-71%, the communication with the receiving hospital in 45-52%, and the transfer management in 52-86%. Patients with a positive prehospital FAST achieved definitive diagnosis or treatment more rapidly (severity-adjusted pooled time ratio = 0.63 [95% CI: 0.41 - 0.95]) compared with patients with a negative or not performed prehospital FAST. CONCLUSIONS: Prehospital FAST had a low sensitivity but a very high specificity to identify hemoperitoneum and reduced time-to-diagnostics or interventions, without increasing prehospital times, in patients with a high probability of abdominal bleeding. Its effect on mortality is still under-investigated.

Factors influencing prehospital physicians' decisions to initiate advanced resuscitation for asystolic out-of-hospital cardiac arrest patients.

BACKGROUND: The decision to initiate or continue advanced life support (ALS) in out-of-hospital cardiac arrest (OHCA) could be difficult due to the lack of information and contextual elements, especially in non-shockable rhythms. This study aims to explore factors associated with clinicians' decision to initiate or continue ALS and the conditions associated with higher variability in asystolic patients. METHODS: This retrospective observational study enrolled 2653 asystolic patients on whom either ALS was attempted or not by the emergency medical services (EMS) physician. A multivariable logistic regression analysis was performed to find the factors associated with the decision to access ALS. A subgroup analysis was performed on patients with a predicted probability of ALS between 35% and 65%. The single physician's behaviour was compared to that predicted by the model taking into account the entire agency. RESULTS: Age, location of event, bystander cardiopulmonary resuscitation and EMS-witnessed event were independent factors influencing physicians' choices about ALS. Non-medical OHCA, younger patients, less experienced physicians, presence of breath activity at the emergency call and a longer time for ALS arrival were more frequent among cases with an expected higher variability in behaviours with ALS. Significant variability was detected between physicians. CONCLUSIONS: Significant inter-physician variability in access to ALS could be present within the same EMS, especially among less experienced physicians, non-medical OHCA and in presence of signs of life during emergency call. This arbitrariness has been observed and should be properly addressed by EMS team members as it raises ethical issues regarding the disparity in treatment.

Multicentre observational study on practice of prehospital management of hypotensive trauma patients: the SPITFIRE study protocol.

INTRODUCTION: Major haemorrhage after injury is the leading cause of preventable death for trauma patients. Recent advancements in trauma care suggest damage control resuscitation (DCR) should start in the prehospital phase following major trauma. In Italy, Helicopter Emergency Medical Services (HEMS) assist the most complex injuries and deliver the most advanced interventions including DCR. The effect size of DCR delivered prehospitally on survival remains however unclear. METHODS AND ANALYSIS: This is an investigator-initiated, large, national, prospective, observational cohort study aiming to recruit >500 patients in haemorrhagic shock after major trauma. We aim at describing the current practice of hypotensive trauma management as well as propose the creation of a national registry of patients with haemorrhagic shock. PRIMARY OBJECTIVE: the exploration of the effect size of the variation in clinical practice on the mortality of hypotensive trauma patients. The primary outcome measure will be 24 hours, 7-day and 30-day mortality. Secondary outcomes include: association of prehospital factors and survival from injury to hospital admission, hospital length of stay, prehospital and in-hospital complications, hospital outcomes; use of prehospital ultrasound; association of prehospital factors and volume of first 24-hours blood product administration and evaluation of the prevalence of use, appropriateness, haemodynamic, metabolic and effects on mortality of prehospital blood transfusions. INCLUSION CRITERIA: age >18 years, traumatic injury attended by a HEMS team including a physician, a systolic blood pressure <90 mm Hg or weak/absent radial pulse and a confirmed or clinically likely diagnosis of major haemorrhage. Prehospital and in-hospital variables will be collected to include key times, clinical findings, examinations and interventions. Patients will be followed-up until day 30 from admission. The Glasgow Outcome Scale Extended will be collected at 30 days from admission. ETHICS AND DISSEMINATION: The study has been approved by the Ethics committee 'Comitato Etico di Area Vasta Emilia Centro'. Data will be disseminated to the scientific community by abstracts submitted to international conferences and by original articles submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04760977.

External validation and insights about the calibration of the return of spontaneous circulation after cardiac arrest (RACA) score.

Background: The return of spontaneous circulation (ROSC) after cardiac arrest (RACA) score was developed as a tool to predict ROSC probability (pROSC) based on easily available information and it could be useful to compare the performances of different EMS agencies or the effects of eventual interventions.We performed an external validation of the RACA score in a cohort of out of hospital cardiac arrest (OHCA) patients managed by the EMS of the metropolitan city of Bologna, Italy. Methods: We analyzed data from 2,310 OHCA events prospectively collected between January 2009 and June 2021. Discrimination was assessed with the area under the ROC curve (AUROC), while the calibration belts were used for the comparison of observed versus expected ROSC rates. The AUROCs from our cohort and other validation cohorts were compared using a studentized range test. Results: The AUROC for the study population was 0.691, comparable to that described by previous validation studies. Despite an acceptable overall calibration, we found a poor calibration for asystole and low pROSC ranges in PEA and shockable rhythms. The model showed a good calibration for patients aged over 80, while no differences in performance were found when evaluating events before and after the implementation of 2015 ERC guidelines. Conclusions: Despite AUROC values being similar in different validation studies for RACA score, we suggest separating the different rhythms when assessing ROSC probability with the RACA score, especially for asystole.

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in Non-Traumatic Cardiac Arrest: A Narrative Review of Known and Potential Physiological Effects.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is widely used in acute trauma care worldwide and has recently been proposed as an adjunct to standard treatments during cardiopulmonary resuscitation in patients with non-traumatic cardiac arrest (NTCA). Several case series have been published highlighting promising results, and further trials are starting. REBOA during CPR increases cerebral and coronary perfusion pressure by increasing the afterload of the left ventricle, thus improving the chances of ROSC and decreasing hypoperfusion to the brain. In addition, it may facilitate the termination of malignant arrhythmias by stimulating baroreceptor reflex. Aortic occlusion could mitigate the detrimental neurological effects of adrenaline, not only by increasing cerebral perfusion but also reducing the blood dilution of the drug, allowing the use of lower doses. Finally, the use of a catheter could allow more precise hemodynamic monitoring during CPR and a faster transition to ECPR. In conclusion, REBOA in NTCA is a feasible technique also in the prehospital setting, and its use deserves further studies, especially in terms of survival and good neurological outcome, particularly in resource-limited settings.

The role of prehospital ultrasound in reducing time to definitive care in abdominal trauma patients with moderate to severe liver and spleen injuries.

BACKGROUND: The role of prehospital focused assessment sonography for trauma (FAST) is still under debate and no definitive recommendations are available in actual guidelines, moreover, the availability of ultrasound machines in emergency medical services (EMS) is still inhomogeneous. On the other hand, time to definitive care is strictly related to survival in bleeding trauma patients. This study aimed at investigating if a positive prehospital FAST in abdominal trauma patients could have a role in reducing door-to-CT scan or door-to-operating room (OR) time. METHODS: This retrospective observational study included all the patients affected by an abdominal trauma with an abdominal abbreviated injury score ≥ 2 and a spleen or liver injury admitted to Maggiore Hospital Carlo Alberto Pizzardi, a level 1 trauma centre between 2014 and 2019. Prehospital and emergency department (ED) clinical and laboratory variables were collected, as well as in-hospital times during the diagnostic and therapeutic pathways of these patients. RESULTS: 199 patients were included in the final analysis. Of these, 44 had a prehospital FAST performed and in 27 of them, peritoneal free fluid was detected in the prehospital setting, while 128 out of 199 patients had a positive ED-FAST. Sensitivity was 62.9% (95% CI: 42.4%-80.6%) and specificity 100% (95% CI: 80.5% - 100%). Patients with a positive prehospital FAST reported a significantly lower door-to-CT or door-to-OR median time (46 vs 69 min, p < 0.001). Prehospital hypotension and Glasgow coma scale, first arterial blood lactate, ISS, age, positive prehospital and ED FAST were inserted in a stepwise selection for a multivariable Cox proportional regression hazards model. Only ISS and prehospital FAST resulted significantly associated with a reduction in the door-to-CT scan or door-to-operating theatre time in the multivariable model. CONCLUSION: Prehospital FAST information of intraperitoneal free fluid could significantly hasten door-to-CT scan or door-to-operating theatre time in abdominal trauma patients if established hospital response protocols are available. LEVEL OF EVIDENCE: III, (Therapeutic / Care Management).

Resuscitative endovascular occlusion of the aorta (REBOA) for refractory out of hospital cardiac arrest. An Utstein-based case series.

AIMS: Out of hospital cardiac arrest (OHCA) is still a leading cause of mortality worldwide. In recent years, resuscitative endovascular balloon occlusion of the aorta (REBOA) has been progressively studied as an adjunct to standard advanced life support (ALS) in both traumatic and non-traumatic refractory OHCA. Since January 2019, the REBOA procedure has been applied to all the patients experiencing both traumatic and non-traumatic refractory OHCA (≥15 min of cardiopulmonary resuscitation) not eligible for ECPR for clinical or logistic reasons. We aimed at describing the feasibility and effects of REBOA performed both in the Emergency Department and in the pre-hospital environment served by the local HEMS for refractory OHCA. METHODS: Twenty consecutive patients experiencing refractory OHCA and in whom REBOA was attempted in 2019 and 2020 were included in the study, Utstein data and REBOA specific variables were recorded. RESULTS: Successful catheter placement was achieved in 18 out of 20 patients, 11 of these were non-traumatic OHCAs while 7 were traumatic OHCAs, the 2 failures were related to repeated arterial puncture failure. Median time between the EMS dispatch and REBOA catheter placing attempt was 46 min. An increase in etCO2 over 10 mmHg was observed after balloon inflation in 12 out of 18 patients (8/11 non-traumatic and 4/7 traumatic OHCAs), a sustained ROSC was observed in 5 patients (1 traumatic and 4 non-traumatic OHCA) that were subsequently admitted to the ICU. Four out of the 5 patients reached the criteria for brain death in the subsequent 24 h while one patient experienced another episode of refractory cardiac arrest in ICU and subsequently died. CONCLUSION: Our data confirm the feasibility of REBOA technique as an adjunct to ALS in both the ED and prehospital phase and most of the treated patients experienced a transient ROSC after balloon inflation while 5 out of 18 experienced a sustained ROSC. However, while in the trauma setting increasing evidence suggests an improved survival when REBOA is applied to refractory OHCA, in non-traumatic OHCA this has yet to be demonstrated and large studies are needed.

Remodelling of a regional emergency hub in response to the COVID-19 outbreak in Emilia-Romagna.

Emilia-Romagna was one of the most affected Italian regions during the COVID-19 outbreak in February 2020. We describe here the profound regional, provincial and municipal changes in response to the COVID-19 pandemic, to cope with the numbers of patients presenting with COVID-19 illness, as well as coping with the ongoing need to care for patients presenting with non-COVID-19 emergencies. We focus on the structural and functional changes in one particular hospital within the city of Bologna, the regional capital, which acted as the central emergency hub for time-sensitive pathologies for the province of Bologna. Finally, we present the admissions profile to our emergency department in relation to the massive increase of infected patients observed in our region as well as the organisational response to prepare for the second wave of the pandemic.

Diagnostic pathways in major trauma patients admitted to Italian hospitals: survey and discussion points from the trauma update 2019.

BACKGROUND: Major trauma is a leading cause of mortality, morbidity, and disability. Severe trauma patients are taken to hospital with multiple suspected injuries and need urgent diagnosis in order to achieve focused and lifesaving interventions. The primary endpoint of this survey was to evaluate the intrahospital diagnostic paths that trauma patients undergo in Italian hospitals. Thus, during the 14th Italian Trauma Network Congress (Trauma UpDate, Bologna, February 2019), we collected and discussed data from Italian hospitals regarding the usual diagnostic pathway for major trauma patients. METHODS: Three sets of multiple closed questions, designed to measure the structure, protocols, and habits of Italian hospitals were sent prior to the congress. The questionnaire was developed on the basis of the available literature and expert opinion, regarding: (1) the role of E-FAST, chest and pelvis radiographs in stable major trauma patients; (2) diagnostic pathways after the first-level imaging in major trauma patients, focused on a number of clinical scenarios; (3) diffusion and knowledge of trauma-specific computed tomography (CT) protocols and fast radiologic reporting. RESULTS: We obtained a total of 232 responses to our survey. A remarkable heterogeneity was found between hub and spoke hospitals regarding the indications to the first- and second-level diagnostics, and their use before centralization to trauma centers of patients admitted to peripheral hospitals. CONCLUSION: Italian hospitals show a high heterogeneity in the diagnostic pathways proposed to major trauma victims, an interdisciplinary revision of local protocols taking into account hospital capabilities, new evidence, and emergency system geographical distribution is strongly recommended.

Resuscitative Endovascular Balloon Occlusion of the Aorta for Refractory Out-of-Hospital Non-Traumatic Cardiac Arrest - A Case Report.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a percutaneous transfemoral balloon technique used in select centers for resuscitation and temporary hemostasis of bleeding patients. Several animal studies demonstrated that its application in non-traumatic cardiac arrest could enhance cerebral and coronary perfusion during cardiopulmonary resuscitation (CPR); despite this, there are few reports of its application in humans. This is a case report of REBOA application during a refractory out-of-hospital cardiac arrest in a 50-year-old man where Advanced Cardiac Life Support (ACLS) alone was unable to maintain a stable return of spontaneous circulation (ROSC) and Extracorporeal Cardiac Life Support (ECLS) was not available.

In vivo dissection of the Helicobacter pylori Fur regulatory circuit by genome-wide location analysis.

Iron homeostasis is particularly important in pathogenic bacteria, which need to compete with the host for this essential cofactor. In Helicobacter pylori, a causative agent of several gastric pathologies, iron uptake and storage genes are regulated at the transcriptional level by the ferric uptake regulator Fur. The regulatory circuit of Fur has recently come under focus because of an intimate interlink with a broader regulatory network governing metal homeostasis, acidic response, and virulence. To dissect the Fur regulatory circuit and identify in vivo targets of regulation, we developed a genome-wide location analysis protocol which allowed the identification of 200 genomic loci bound by Fur as well as the investigation of the binding efficiency of the protein to these loci in response to iron. Comparative analysis with transcriptomes of wild-type and fur deletion mutant strains allowed the distinction between targets associated with Fur regulation and genes indirectly influenced by the fur mutation. The Fur regulon includes 59 genes, 25 of which appear to be positively regulated. A case study conducted by primer extension analysis of two oppositely regulated genes, hpn2 and flaB, suggests that negative regulation as well as positive regulation occurs at the transcriptional level. Furthermore, the results revealed the existence of 13 Fur targeted loci within polycistronic operons, which were associated with transcript deregulation in the fur mutant strain. This study provides a systematic insight of Fur regulation at the genome-wide level in H. pylori and points to regulatory functions extending beyond the classical Fur repression paradigm.