Molecular surveillance of multidrug-resistant Gram-negative bacteria in Ukrainian patients, Germany, March to June 2022.

BackgroundSince the beginning of the war in Ukraine in February 2022, Ukrainians have been seeking shelter in other European countries.AimWe aimed to investigate the prevalence and the molecular epidemiology of multidrug-resistant Gram-negative (MDRGN) bacteria and meticillin-resistant Staphylococcus aureus (MRSA) in Ukrainian patients at admittance to the University Hospital Frankfurt, Germany.MethodsWe performed screening and observational analysis of all patients from March until June 2022. Genomes of MDRGN isolates were analysed for antimicrobial resistance, virulence genes and phylogenetic relatedness.ResultsWe included 103 patients (median age: 39 ±â€¯23.7 years), 57 of whom were female (55.3%; 95% confidence interval (CI): 45.2-5.1). Patients were most frequently admitted to the Department of Paediatrics (29/103; 28.2%; 95% CI: 19.7-37.9). We found 34 MDRGN isolates in 17 of 103 patients (16.5%; 95% CI: 9.9-25.1). Ten patients carried 21 carbapenem-resistant (CR) bacteria, five of them more than one CR isolate. Four of six patients with war-related injuries carried eight CR isolates. In six of 10 patients, CR isolates caused infections. Genomic characterisation revealed that the CR isolates harboured at least one carbapenemase gene, bla NDM-1 being the most frequent (n = 10). Core genome and plasmid analysis revealed no epidemiological connection between most of these isolates. Hypervirulence marker genes were found in five of six Klebsiella pneumoniae CR isolates. No MRSA was found.ConclusionHospitals should consider infection control strategies to cover the elevated prevalence of MDRGN bacteria in Ukrainian patients with war-related injuries and/or hospital pre-treatment and to prevent the spread of hypervirulent CR isolates.

Resistance patterns and clinical outcomes of Klebsiella pneumoniae and invasive Klebsiella variicola in trauma patients.

Recent reclassification of the Klebsiella genus to include Klebsiella variicola, and its association with bacteremia and mortality, has raised concerns. We examined Klebsiella spp. infections among battlefield trauma patients, including occurrence of invasive K. variicola disease. Klebsiella isolates collected from 51 wounded military personnel (2009-2014) through the Trauma Infectious Disease Outcomes Study were examined using polymerase chain reaction (PCR) and pulsed-field gel electrophoresis. K. variicola isolates were evaluated for hypermucoviscosity phenotype by the string test. Patients were severely injured, largely from blast injuries, and all received antibiotics prior to Klebsiella isolation. Multidrug-resistant Klebsiella isolates were identified in 23 (45%) patients; however, there were no significant differences when patients with and without multidrug-resistant Klebsiella were compared. A total of 237 isolates initially identified as K. pneumoniae were analyzed, with 141 clinical isolates associated with infections (remaining were colonizing isolates collected through surveillance groin swabs). Using PCR sequencing, 221 (93%) isolates were confirmed as K. pneumoniae, 10 (4%) were K. variicola, and 6 (3%) were K. quasipneumoniae. Five K. variicola isolates were associated with infections. Compared to K. pneumoniae, infecting K. variicola isolates were more likely to be from blood (4/5 versus 24/134, p = 0.04), and less likely to be multidrug-resistant (0/5 versus 99/134, p<0.01). No K. variicola isolates demonstrated the hypermucoviscosity phenotype. Although K. variicola isolates were frequently isolated from bloodstream infections, they were less likely to be multidrug-resistant. Further work is needed to facilitate diagnosis of K. variicola and clarify its clinical significance in larger prospective studies.

Life on the battlefield: Valproic acid for combat applications.

The leading causes of death in military conflicts continue to be hemorrhagic shock (HS) and traumatic brain injury (TBI). Most of the mortality is a result of patients not surviving long enough to obtain surgical care. As a result, there is a significant unmet need for a therapy that stimulates a "prosurvival phenotype" that counteracts the cellular pathophysiology of HS and TBI to prolong survival. Valproic acid (VPA), a well-established antiepileptic therapy for more than 50 years, has shown potential as one such prosurvival therapy. This review details how VPA's role as a nonselective histone deacetylase inhibitor induces cellular changes that promote survival and decrease cellular pathways that lead to cell death. The review comprehensively covers more than two decades worth of studies ranging from preclinical (mice, swine) to recent human clinical trials of the use of VPA in HS and TBI. Furthermore, it details the different mechanisms in which VPA alters gene expression, induces cytoprotective changes, attenuates platelet dysfunction, provides neuroprotection, and enhances survival in HS and TBI. Valproic acid shows real promise as a therapy that can induce the prosurvival phenotype in those injured during military conflict.

Tranexamic acid in pediatric combat trauma requiring massive transfusions and mortality.

BACKGROUND: Tranexamic acid (TXA) has been demonstrated to decrease mortality in adult trauma, particularly in those with massive transfusions needs sustained in combat injury. Limited data are available for the efficacy of TXA in pediatric trauma patients outside of a single combat support hospital in Afghanistan. METHODS: The Department of Defense Trauma Registry was queried for trauma patients younger than 18 years from Iraq and Afghanistan requiring 40 mL/kg or greater of blood product within 24 hours of injury. Burns and fatal head traumas were excluded. Primary outcome was in-hospital mortality. Secondary outcomes were hospital, ventilator, and intensive care unit-free days, as well as total blood product volume. RESULTS: Among those pediatric patients receiving massive transfusions, those who received TXA were less likely to die in hospital (8.5% vs. 18.3%). Patients who received TXA and those who did not have similar hospital-free days (19 vs. 20), ventilator-free days (27 vs. 27), and intensive care unit-free days (25 vs. 24). Those who received TXA had higher 24-hour blood product administration (100 mL/kg vs. 75 mL/kg). None of our results rose to the level of statistical significance. The TXA administration significantly reduced odds of death on logistic regression (odds ratio, 0.35; 95% confidence interval, 0.123-0.995; p = 0.0488). CONCLUSION: Use of TXA in pediatric patients with combat trauma requiring massive transfusions trended toward a significant improvement in in-hospital mortality (p = 0.055). This mortality benefit is similar to that seen in adult studies and a less well characterized cohort in another pediatric study suggesting TXA administration confers mortality benefit in massively transfused pediatric combat trauma victims. LEVEL OF EVIDENCE: Evidence (retrospective cohort), Level IV.

Use of ketamine for prehospital pain control on the battlefield: A systematic review.

BACKGROUND: Intravenous ketamine is commonly used for pain management in the civilian prehospital setting. Several studies have evaluated its effectiveness in the military setting. To date, there has been no report reviewing the published data on the use of ketamine in this context. The objective of this systematic review was to analyze the content and quality of published data on the use of ketamine for prehospital pain management in military trauma. METHODS: The MEDLINE database was searched for studies on ketamine use in combat prehospital settings, at point of injury or during evacuation, published between 2000 and 2019. The systematic review was conducted following PRISMA guidelines, and the protocol was registered on PROSPERO (CRD42019115728). Civilian reports and case series lacking systematic data collection were excluded. RESULTS: Eight studies were included with 2029 casualties receiving ketamine. All but one were American reports from Afghanistan and Iraq conflicts. Studies implied retrospective cohorts or prospective observational analysis. Ketamine use rose from 3.9% during the period preceding its addition to the Tactical Combat Casualty Care guidelines in 2012 to 19.8% thereafter. It was the most common analgesic administered (up to 52% of casualties) in one of the studies. Ketamine was more likely given during tactical medical evacuation when no analgesic was provided at the point of injury. The median total intravenous dose was 50 mg. Pain intensity decreased from moderate or severe to mild or none, sometimes after only one dose. In one study, ketamine administration during tactical evacuation was associated with increased systolic blood pressure as opposed to morphine. Incoherent speech, extremity movements, and hallucinations were the main adverse events reported. CONCLUSION: Published data on ketamine use in military trauma are rare and heterogeneous. Though, all studies tend to strengthen the belief in the efficacy and safety of ketamine when given at 50-mg to 100-mg intravenous for prehospital analgesia in combat casualties. LEVEL OF EVIDENCE: Systematic Review, Level IV.

Prehospital ketamine administration to pediatric trauma patients with head injuries in combat theaters.

BACKGROUND: Head injuries frequently occur in combat. Tactical Combat Casualty Care (TCCC) guidelines recommend pre-hospital use of ketamine for analgesia. Yet the use of this medication in patients with head injuries remains controversial, particularly among pediatric patients. We compare survival to hospital discharge rates among pediatric head injury subjects who received prehospital ketamine versus those who did not. METHODS: We queried the Department of Defense Trauma Registry (DODTR) for all pediatric (<18 years of age) subjects from January 2007 to January 2016. We performed a sub-analysis of subjects with an abbreviated injury severity score for the head of 3 (serious) or higher and at least one documented Glasgow Coma Score (GCS) ≤13. RESULTS: Of the 3439 pediatric patients within our dataset, 555 subjects met inclusion criteria for head injury - 36 (6.5%) received prehospital ketamine versus 519 (93.5%) who did not. There was no significant difference noted between groups regarding median age (10 versus 8, p = 0.259), percent male gender (72.2% versus 76.3%, p = 0.579), mechanism of injury (p = 0.143), median composite injury scores (22 versus 20, p = 0.082), median ventilator-free days (28 versus 27, p = 0.068), median ICU-free days (27.5 versus 27, p = 0.767), median hospital days (3.5 versus 4, p = 0.876) or survival to discharge (66.7% versus 70.7%, p = 0.607). CONCLUSIONS: Within this data set, we were unable to detect any differences in mortality among pediatric head trauma subjects administered ketamine compared to subjects not receiving this medication in the prehospital setting.

Prehospital Application of Hemostatic Agents in Iraq and Afghanistan.

INTRODUCTION: Hemorrhage is the leading cause of death on the battlefield. Development of chitosan- and kaolin-based hemostatic agents has improved hemorrhage control options. Sparse data exists on the use of these agents in the prehospital, combat setting. We describe recent use of these agents and compare patients receiving hemostatic to the baseline population. METHODS: We used a series of emergency department (ED) procedure codes to identify patients within the Department of Defense Trauma Registry (DODTR) from January 2007 to August 2016. We only included patients for whom the DODTR specified the hemostatic agent utilized (chitosan or kaolin). We defined a serious injury by body region as an Abbreviated Injury Score (AIS) of 3 or greater. RESULTS: Our predefined search codes captured 28,222 patients. Of those, 258 (0.9%) patients had documented hemostatic use: 58 chitosan, 201 kaolin, and one subject received both. Patients undergoing hemostatic agent application were more likely to be injured by gunshot wound or explosive. Patients with hemostatic application had higher median composite Injury Severity Scores (10 vs. 9, p < 0.001), and higher AIS for the abdomen, extremity and superficial body regions with higher rates of blood product utilization. Proportions of patients suffering traumatic amputations and undergoing tourniquet application were higher in the hemostatic agent group than the baseline population (11.6% vs. 6.7%, p = 0.002 and 43.4% vs. 13.8%, p < 0.001, respectively). CONCLUSIONS: Hemostatic agents were infrequently utilized to manage traumatic hemorrhage during the recent conflicts in Afghanistan and Iraq. Hemostatic agent use was more frequent in casualties with gunshot wounds, traumatic amputations, concomitant tourniquet application, and greater blood product administration."

Prehospital Analgesia for Pediatric Trauma Patients in Iraq and Afghanistan.

BACKGROUND: Previous studies have evaluated prehospital analgesia during combat operations in Iraq and Afghanistan, but were limited to the adult population. However, a significant portion of the casualties of those conflicts were children. We describe the prehospital analgesia administered to wartime pediatric trauma patients. METHODS: We queried the Department of Defense Trauma Registry (DODTR) for all pediatric patients (<18 years of age) admitted to United States and Coalition fixed-facility hospitals in Iraq and Afghanistan from January 2007 to January 2016. We divided pediatric patients into 2 groups: those that had documentation of receipt of analgesic drugs in the prehospital setting (n = 618) and those who had not received analgesia before reaching a fixed-facility (n = 2,821). For characterization of drug administration, we grouped patients into those receiving acetaminophen, NSAID, fentanyl, ketamine, morphine, or other analgesics (e.g., hydromorphone, tramadol, etc.). RESULTS: During the study period, there were 3,439 pediatric encounters with documentation of 703 instances of analgesia administrations to 618 patients (17.9% of total pediatric encounters). Of the subjects receiving analgesic agents, 46.2% (n = 325) received morphine, 30.4% (n = 214) received fentanyl, 17.4% (n = 122) received ketamine, 1.8% (n = 13) received acetaminophen, and 2.8% (n = 20) received a non-steroidal anti-inflammatory drug. The remaining 9 administrations consisted of methoxyflourane (1), nalbuphine (2), hydromorphone (3), and tramadol (3). An injury severity score (ISS) >15 increased the odds of receiving an analgesic agent (OR 1.26, 95% CI 1.02-1.56). Additionally, there was an association between analgesia administration and the following prehospital interventions: wound dressing, tourniquet, intravenous (IV) line placement, intraosseous line placement, IV fluids, intubation, and external warming. CONCLUSIONS: Overall, a low proportion of pediatric trauma subjects within this population received analgesia in the prehospital environment. The most common analgesic medication administered was morphine. Those receiving analgesic agents had more severe injuries and higher rates of concomitant interventions. These results highlight the potential need for Tactical Combat Casualty Care guidelines specifically providing recommendations for analgesia administration among pediatric patients.

Prehospital Administration of Tranexamic Acid by Ground Forces in Afghanistan: The Prehospital Trauma Registry Experience.

BACKGROUND: Tranexamic acid (TXA) was shown to reduce overall mortality and death secondary to hemorrhage in a large prospective study. This intervention is time sensitive. As such, the Tactical Combat Casualty Care (TCCC) guidelines recommend use of this low-cost, safe intervention among patients with possible hemorrhagic shock, penetrating trauma to the thorax or trunk, or extremity amputation. OBJECTIVE: Prehospital administration of TXA by ground forces in the Afghanistan combat theater is described. METHODS: We obtained data from the Prehospital Trauma Registry. We searched for all patients with documented hypotension, amputation, or penetrating trauma to the torso. RESULTS: From January 2013 to September 2014, there were 272 patients who met inclusion criteria. Most injuries (97.8%; n = 266) were battle injuries. Of the 272 patients who met criteria to receive prehospital TXA, 51 (18.8%) received TXA, whereas the remaining 221 (81.2%) did not. Higher proportions of patients receiving TXA versus patients not receiving TXA received hemostatic dressings, pressure dressings, and tourniquet placement. Conversely, the proportion of patients receiving intravenous fluids was higher in the no-TXA group. CONCLUSION: Overall, proportions of eligible patients receiving TXA were low despite emphasis in the guidelines. The reasons for this low adherence to TCCC guidelines are likely multifactorial. Future research should seek to identify reasons TXA is not given when indicated and to develop training and technology to increase prehospital TXA administration.

[The treatment of wounds during World War I].

The First World War was a huge tragedy for mankind, but, paradoxically, it represented a source of significant progress in a broad series of human activities, including medicine, since it forced physicians to improve their knowledge in the treatment of a large number of wounded soldiers. The use of heavy artillery and machine guns, as well as chemical warfare, caused very serious and life-threatening lesions and wounds. The most frequent causes of death were not mainly related to gunshot wounds, but rather to fractures, tetanus and septic complications of infectious diseases. In the first part of this article, we describe the surgical procedures and medical therapies carried out by Italian physicians during the First World War, with the aim of treating wounded soldiers in this pre-antibiotic era. Antibacterial solutions, such as those of Dakin-Carrel and sodium hypochlorite and boric acid, the tincture of iodine as well as the surgical and dressing approaches and techniques used to remove pus from wounds, such as ignipuncture and thermocautery or lamellar drainage are reported in detail. In the second part of the paper, the organization of the Italian military hospitals network, the systems and tools useful to transport wounded soldiers both in the front lines and in the rear is amply discussed. In addition, the number of soldiers enrolling, and those dying, wounded or missing during the Great War on the Italian front is estimated.

Battlefield pain management: A view of 17 years in Israel Defense Forces.

BACKGROUND: Pain control in trauma is an integral part of treatment in combat casualty care (CCC). More soldiers injured on the battlefield will need analgesics for pain than those who will need lifesaving interventions (LSI). It has been shown that early treatment of pain improves outcomes after traumatic injury, whereas inadequate treatment leads to higher rates of PTSD. The purpose of this article is to report the Israel Defense Forces Medical Corps (IDF-MC) experience with point of injury (POI) use of analgesia. METHODS: All cases documented in the IDF Trauma Registry (ITR) between January 1997 and December 2014 were examined. All cases of POI pain medications were extracted. Data collection included mechanism of injury, wound distribution, pain medication administered, mortality, and provider type. RESULTS: Of 8,576 patients, 1,056 (12.3%) patients who had at least one documented pain management treatment were included in this study. Demographics of the study population included 94.2% men and 5.8% women with a median age of 21 years. Injury mechanisms included 40.3% blast injuries (n = 426) and 29% gunshot injuries (306). Of 1,513 injured body regions reported, 52% (787) were extremity wounds (upper and lower), 23% (353) were truncal wounds, and 17.7% (268) were head and neck injuries. A total of 1,469 episodes of analgesic treatment were reported. The most common types of analgesics were morphine (74.7%, 1,097 episodes), ketamine (9.6%, 141 episodes), and fentanyl (13.6%, 200 episodes). Of the patients, 39% (413) received more than one type of analgesic. In 90.5% of cases, analgesia was administered by a physician or a paramedic. Over the span of the study period (1997-2014), types of analgesics given by providers at POI had changed, as fentanyl was introduced to providers. A total of 801 LSIs were performed on 379 (35.9%) patients receiving analgesia, and no adverse events were found in any of the casualties. CONCLUSION: Most casualties at POI did not receive any analgesics while on the battlefield. The most common analgesics administered at POI were opioids and the most common route of administration was intravenously. This study provides evidence that over time analgesic administration has gained acceptance and has been more common place on the battlefield. Increasingly, more casualties are receiving pain management treatment early in CCC along with LSIs. We hope that this shift will impact CCC by reducing PTSD and overall morbidity resulting from inadequate management of acute pain.

Prevalence and Predictors of Prehospital Pain Assessment and Analgesic Use in Military Trauma Patients, 2010-2013.

INTRODUCTION: Pain is the most common symptom in patients presenting for prehospital (PH) care. Research in civilian emergency medical systems has shown wide variability in PH pain assessment and analgesic practices, yet a minimal amount is known about pain assessment and analgesic intervention practices in the military, particularly when PH care is delivered in a combat zone. OBJECTIVE: To describe prehospital (PH) pain care practices for U.S. military personnel injured in Iraq and Afghanistan 2010-2013 and explore potential relationships to explain variation. METHODS: An exploratory retrospective, cross-sectional study of Department of Defense Trauma Registry data from 2010 to 2013 was performed. Demographic, clinical, or health system variables for associations with three outcomes: 1) pain assessment documentation; 2) pain severity (0-10 scale); and 3) analgesic administration (yes/no). Including only variables with significant associations, backward stepwise regression was used to develop explanatory models for each outcome. RESULTS: Patient records (n = 3,317) were evaluated for documentation of PH pain assessment and analgesic administration. The prevalence of PH pain score documentation was 37.8% (n = 1,253). Overall, the proportion of records with PH pain scores increased over time: 19.8% (2010), 35.1% (2011), 58.2% (2012), and 62.2% (2013). Severity of pain scores ranged 0-10; mean = 5.5 (SD = 3.1); median = 6 (IQR = 3-8). Analgesics were reported for 50.8% (n = 1,684), of whom 38.3% had a pain severity score documented. The pain assessment documentation model included any documented vital signs, injury year, and mechanism of injury and explained 19.3% of the variance in documentation. The pain severity model included vital signs and injury severity score (ISS) and explained 5.0% of the variance in severity. The analgesic model included any vital signs, pain severity, trauma type, mechanism of injury, ISS, and year. CONCLUSIONS: Pain assessment and treatment documentation improved each year, but remain suboptimal. Available data yielded poor prediction of the outcomes of interest, emphasizing the importance of individual assessment. Analgesic effectiveness could not be evaluated.

Testing of antibiotic releasing implant coatings to fight bacteria in combat-associated osteomyelitis - an in-vitro study.

PURPOSE: Surgical procedures to prevent osteomyelitis after trauma can be supported by local application of antibiotics. This in-vitro study investigated the release and impact of antibiotics from implant coatings against bacteria associated with combat-related osteomyelitis. METHODS: K-wires were coated with poly(D,L-lactide) and ciprofloxacin, gentamicin, colistin, daptomycin or cefoxitin in different concentrations. The release was quantified and antimicrobial activity tested for different gram-positive or gram-negative bacteria, alone and in combination. To exclude toxic effects, primary osteoblast-like cells were exposed to antibiotic coating concentrations. RESULTS: All antibiotics alone and in combination showed an initial burst release with dose dependent antimicrobial activity and no negative effects on osteoblast-like cells, except for cefoxitin. CONCLUSIONS: Implant coatings can be customized with single or double antibiotic coatings to effectively fight different bacteria and also mixed infections in the treatment of a combat-acquired osteomyelitis. However, optimal drug load and degradation behaviour of individual antibiotics have to be considered.

Use of tranexamic acid in combat casualties. Experience of the Spanish medical corps. Clinical series and literature review. / Empleo de ácido tranexámico en el herido de combate, experiencia de la sanidad militar española. Serie de casos y revisión de la literatura.

OBJECTIVE: To describe the experience with tranexamic acid (TXA) during the care of combat causalities treated in the Spanish military hospital based in Herat (Afghanistan) and to perform an analysis of the literature related to the military setting. MATERIAL AND METHODS: With the approval of the appropriate military institutions, an analysis was performed on the use of TXA in combat casualties treated between March and May 2014. Of the 745 patients seen, 10 were due to a firearm/explosive device (combat casualties). A descriptive analysis was performed on the data collected. Absolute and relative frequencies (%) were used for the categorical variables. For central tendency measurements, the arithmetic mean and standard deviation or the median and interquartile range was calculated. The data were obtained from the military records of patients treated in the Herat military hospital. RESULTS: All the patients in this series received TXA within the first 3 hours after the attack. The most frequent dose used was one gram i.v, with bleeding was controlled in 100% of cases. All the patients survived and none of them had secondary effects. These data agree with that recommended in the combat casualties treatment guide followed by military health in other countries in this setting. CONCLUSION: All combat casualties were treated with TXA within the first 3 hours. The most frequent dose used was one gram iv and bleeding was controlled in all cases. All the patients survived with no adverse effects being observed.

Prehospital pain medication use by U.S. Forces in Afghanistan.

We report the results of a process improvement initiative to examine the current use and safety of prehospital pain medications by U.S. Forces in Afghanistan. Prehospital pain medication data were prospectively collected on 309 casualties evacuated from point of injury (POI) to surgical hospitals from October 2012 to March 2013. Vital signs obtained from POI and flight medics and on arrival to surgical hospitals were compared using one-way analysis of variance test. 119 casualties (39%) received pain medication during POI care and 283 (92%) received pain medication during tactical evacuation (TACEVAC). Morphine and oral transmucosal fentanyl citrate were the most commonly used pain medications during POI care, whereas ketamine and fentanyl predominated during TACEVAC. Ketamine was associated with increase in systolic blood pressure compared to morphine (+7 ± 17 versus -3 ± 14 mm Hg, p = 0.04). There was no difference in vital signs on arrival to the hospital between casualties who received no pain medication, morphine, fentanyl, or ketamine during TACEVAC. In this convenience sample, fentanyl and ketamine were as safe as morphine for prehospital use within the dose ranges administered. Future efforts to improve battlefield pain control should focus on improved delivery of pain control at POI and the role of combination therapies.

[COMPLEX OF THE TREATMENT MEASURES IN A SYSTEM OF THE MEDICAL CARE DELIVERY TO WOUNDED PERSONS WITH THE GUN-SHOT AND MINE-EXPLOSIVE INJURIES OF THE FOOT].

Complex of the treatment measures, conducted in 302 wounded persons, suffering the gun-shot and mine-explosive injuries of the foot in 2014 - 2015 yrs, was analyzed. Primary surgical processing of the wound was conducted in all injured persons, secondary surgical processing--in 64.6%, the foot bones osteosynthesis--in 13.9%, primary immobilization, using improvised tire--in 77.8%, secondary immobilization, using the plaster splint--in 48.1%, llizarov's spokes--in 35.2%, Ilizarov's apparatus--in 18.5%, the rods apparatuses of external fixation--in 16.7%. For improvement of functioning of a modern system for the treatment-evacuation provision it is necessary, to reduce the quantity of levels of the medical help provision maximally.