Predictors of Short-Term Trauma Laparotomy Outcomes in an Integrated Military-Civilian Health System: A 23-Year Retrospective Cohort Study.

Background: Trauma laparotomy (TL) remains a cornerstone of trauma care. We aimed to investigate prehospital measures associated with in-hospital mortality among casualties subsequently undergoing TLs in civilian hospitals. Methods: This retrospective cohort study cross-referenced the prehospital and hospitalization data of casualties treated by Israel Defense Forces-Medical Corps teams who later underwent TLs in civilian hospitals between 1997 and 2020. Results: Overall, we identified 217 casualties treated by IDF-MC teams that subsequently underwent a TL, with a mortality rate of 15.2% (33/217). The main mechanism of injury was documented as penetrating for 121/217 (55.8%). The median heart rate and blood pressure were within the normal limit for the entire cohort, with a low blood pressure predicting mortality (65 vs. 127, p < 0.001). In a multivariate analysis, prehospital endotracheal intubation (ETI), emergency department Glasgow coma scores of 3-8, and the need for a thoracotomy or bowel-related procedures were significantly associated with mortality (OR 6.8, p < 0.001, OR = 48.5, p < 0.001, and OR = 4.61, p = 0.002, respectively). Conclusions: Prehospital interventions introduced throughout the study period did not lead to an improvement in survival. Survival was negatively influenced by prehospital ETI, reinforcing previous observations of the potential deleterious effects of definitive airways on hemorrhaging trauma casualties. While a low blood pressure was a predictor of mortality, the median systolic blood pressure for even the sickest patients (ISS > 16) was within normal limits, highlighting the challenges in triage and risk stratification for trauma casualties.

Discovery of Selective Tertiary Amide Inhibitors of Cyclin-Dependent Kinase 2 (CDK2).

Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and are frequently altered in cancer cells, thereby leading to uncontrolled proliferation. In this context, CDK2 has emerged as an appealing target for anticancer drug development. Herein, we describe the discovery of a series of selective small molecule inhibitors of CDK2 beginning with historical compounds from our ERK2 program (e.g., compound 6). Structure-based drug design led to the potent and selective tool compound 32, where excellent selectivity against ERK2 and CDK4 was achieved by filling the lipophilic DFG-1 pocket and targeting interactions with CDK2-specific lower hinge binding residues, respectively. Compound 32 demonstrated 112% tumor growth inhibition in mice bearing OVCAR3 tumors with 50 mg/kg bis in die (BID) oral dosing.

Effectiveness and Safety of Remote Cardiac Rehabilitation for Patients After Acute Coronary Syndrome.

Cardiac rehabilitation improves cardiovascular outcomes in patients after acute coronary syndrome (ACS). Recently there has been a growing interest in remote cardiac rehabilitation (RCR) programs. We aimed to evaluate the effectiveness of RCR compared with center-based cardiac rehabilitation (CBCR). This is an observational study including patients after hospital admission for ACS. The study group included patients at low-to-moderate risk for cardiovascular complications who were referred for RCR. The control group included patients at similar risk who participated in CBCR. The primary end points were the improvement of at least 10% to 25% in exercise capacity after 6 months of cardiac rehabilitation. Included were 305 patients who completed 6 months of cardiac rehabilitation. Of them, 107 patients participated in RCR and 198 in CBCR. RCR patients were younger and more frequently males. Improvement of ≥10% in exercise capacity after 6 months was achieved more frequently in patients participating in RCR compared with CBCR (69.3% and 55% respectively, p = 0.03). A similar trend was observed for improvement of ≥25% in exercise capacity after 6 months (33.8% and 22.7% in RCR and CBCR, respectively, p = 0.05). While weight reduction and the increase in muscle mass were similar in the 2 groups, fat percent reduction was significantly greater in the RCR compared with the CBCR (2.5% and 1.4% respectively, p <0.005). We conclude that RCR program is an effective and safe option for low-risk patients after hospital admission for ACS. It enables optimizing the utilization of this important service for patients with coronary artery disease.

Isolated limb fractures - the underestimated injury in the Israeli Defence Forces (IDF).

INTRODUCTION: Musculoskeletal injuries dominate warfare-related trauma and differ from civilian settings in higher hospitalization costs, morbidity, and mortality. Partly due to introduction of personal protective equipment in the Israel Defence Force (IDF) to minimize head and torso injuries while the extremities remained unprotected. This study describes military extremity injury patterns, prehospital treatment and injury sequela regarding return-to-duty and disability compensation. METHODS: This retrospective study examined cases of battle and non-battle trauma casualties treated by the IDF Medical Corps from 2013 to 2020. Data from the IDF Trauma Registry (IDF-TR) was merged with The Israeli National Trauma Registry (INTR). Cases with high morbidity discharged from military service were compared with lower morbidity patients who returned to active duty service. RESULTS: Out of 1360 injured soldiers, 280 (20.6%) were found to have isolated limb fractures (ILFs). High morbidity casualties had more open fractures (63% vs. 42%) and higher involvement of lower extremities (79% vs. 58%) (p < 0.001), higher rates of tourniquets use (28% compared to 9%, p < 0.001), external fixation (34% vs. 19%, p < 0.001) and amputations (9% vs. 1%, p = 0.003), required more rehabilitation (34% vs. 7%, p < 0.001), and had 46% medical disabilities compared to 24% with low morbidity (p < 0.001). CONCLUSIONS: ILFs are associated with significant morbidity and disability. High morbidity is associated with high energy, scar-producing, lower-extremity open fractured limbs treated by tourniquets. Future studies should evaluate whether junctional or extremity protective gear is combat feasible and whether introducing Clinical Practice Guidelines to manage suspected limb fractures can decrease morbidity rates and improve return to duty.

Ten-year reduction in thoracic injury-related mortality among Israel Defense Forces soldiers.

INTRODUCTION: This study aims to describe injury patterns, prehospital interventions and mortality rates of combat-related thoracic injuries during the past decade among Israel Defense Forces (IDF) soldiers before and after implementation of the 2012 IDF-Military Corps 'My Brother's Keeper' plan which included the publication of clinical practice guidelines (CPGs) for thoracic injuries, emphasis on adequate torso protection, introduction of modern life-saving procedures and encouragement of rapid evacuation. METHODS: The IDF prehospital trauma registry was reviewed to identify all patients who sustained thoracic injuries from January 2006 to December 2017. IDF soldiers who were injured, died of wounds or killed in action (KIA) were included. These were cross-referenced with the Israel National Trauma Registry. The periods before and after the plan were compared. RESULTS: 458 (12.3%) of 3733 IDF soldiers wounded on the battlefield sustained combat-related thoracic injuries. The overall mortality was 44.3% before the CPG and 17.3% after (p<0.001). Most were KIA: 97% (95 of 98) died by 30 June 2012, and 83% (20 of 24) after (p<0.001). Casualties treated with needle thoracostomy before and after CPG were 6.3% and 18.3%, respectively (p=0.002). More tube thoracostomies were performed after June 2012 (16.1% vs 5.4%, p=0.001). Evacuation was faster after June 2012 (119.4 min vs 560.8 min, p<0.001), but the rates of casualties evacuated within 60 min were similar (21.1% vs 25%, p=0.617). CONCLUSIONS: Among military casualties with thoracic injuries, the rate of life-saving interventions increased, evacuation time decreased and mortality dropped following the implementation of My Brother's Keeper plan.

Combat Injury Profile in Urban Warfare.

INTRODUCTION: Combat ground maneuvers consist of various platforms and have several environmental characteristics, influenced by the terrain, the operational mission, and the force's capabilities. This study assesses data on injuries sustained during urban warfare, aiming to evaluate the relationship between injury characteristics, maneuver platform, and personal protective gear on the battlefield. MATERIALS AND METHODS: IDF soldiers injured infantry soldiers from the "Cast Lead" and the "Protective Edge" operations in the Gaza Strip (2008-2009 and 2014, respectively) were divided into four groups according to the maneuver platform and the environment: mounted infantry (armored and unarmored vehicle) and dismounted infantry (urban and open area). The primary outcome was the severity of the injury, and the secondary outcome was the injured body part. RESULTS: Overall, 588 casualties were included in the final analysis, of whom 507 were dismounted infantry soldiers (265 in open terrain and 242 in urban area) and 81 were mounted infantry soldiers (20 in unarmored and 61 were injured in armored vehicles). The Injury Severity Score was similar in all subgroups. Open terrain subgroups were found to have fewer head injuries and higher levels of lower extremity injuries, similar to the unarmored vehicle group. More facial injuries were documented in the urban area group. CONCLUSIONS: The Injury Severity Score was not influenced by environmental protection. Although we found differences in the injured body parts, further studies on the exact mechanism of injury are needed to elucidate further the relationship and differences between the various platforms used and injuries seen in urban warfare, aiming for tailor-made protection.

Elucidating a Potential Mechanism of Permeability Enhancer Sodium N-[8-(2-hydroxybenzoyl) amino] Caprylate in Rats: Evidence of Lymphatic Absorption of Cyanocobalamin using the Mesenteric Lymph Duct Cannulated Rat.

Oral administration is the most popular and convenient route for drug delivery, yet the success of oral drug delivery is dependent on the ADME properties of the drug. Among those ADME properties, permeability is considered one of the key attributes for successful oral drug absorption. Hence, the utilization of permeability enhancers to improve drug oral absorption is an important area of research in drug delivery. A multitude of data suggests that sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) is an effective permeability enhancer. Despite its success, the mechanism of how SNAC works to enhance the oral absorption of compounds is poorly understood. To better understand how SNAC worked, we investigated the hypothesis of SNAC promotes lymphatic absorption of target compounds. In this study, cyanocobalamin was used as the model compound and mesenteric lymph duct cannulated rats were used to investigate its absorption with or without SNAC. The present study demonstrated that SNAC enhanced the lymphatic absorption of cyanocobalamin when the two were co-dosed in rats. Furthermore, levels of SNAC in lymph fluid and the systemic circulation were higher when co-dosed with cyanocobalamin.

Emergent exploratory thoracotomy with military casualties: contemporary prehospital management and outcome (see editorial page 619).

BACKGROUND: Chest trauma is among the most common types of trauma, corresponding to 10% of trauma patients admitted to hospitals. In the military setting, thoracic trauma was reported as a significant cause of death. With well-timed treatment, chest trauma is regarded as survivable. Emergency thoracotomy (ET) is considered when the patient with trauma to the chest needs immediate resuscitation. Survival rate is reported as low as 1% in some reports and 20% in others. The survival rate depends on injury mechanism, protocols for intervention, and other decompressive procedures. OBJECTIVES: To determine parameters that may impact survival of ET. METHODS: We conducted a retrospective cohort study to compare prehospital and in-hospital data regarding ET in the emergency department (ED) versus the operating room (OR). RESULTS: Between 2009 and 2017, 6532 casualties presented to the ED; 1125 with trauma to the chest. Fifty-four of those with chest trauma underwent ET in the hospital (4.8%), 22 (41%) in the ED, and 32 (59%) in the OR. The overall mortality of the ET subgroup was 48%. With regard to thoracotomies, 19/22 of patients (86%) who underwent ET in the ED died compared to 2/28 in the OR (13%). CONCLUSIONS: Utilizing ET after chest trauma with appropriate clinical indications, well-trained personnel, and prompt transportation poses a significant challenge, but may be associated with better survival than that reported previously with military casualties. Adoption of indications and timed allocation to the OR may improve outcomes with chest trauma casualties.

Isolated Versus Non-isolated Traumatic Brain Injuries Identification and Decision Making: A Comparative Study.

BACKGROUND: Traumatic brain injury (TBI) is a significant cause of death in the battlefield. TBI can be challenging to diagnose in the combat setting and remains a substantial challenge for advanced life support (ALS) providers. OBJECTIVES: To compare prehospital and hospitalization characteristics between isolated and non-isolated TBI. To examine the effects of TBI with coexisting injuries on patient evaluation and outcomes based on the Israeli Defense Forces Trauma Registry and the Israeli National Trauma Registry of soldiers hospitalized for TBI between the years 2006-2017. METHODS: A total of 885 casualties were eligible for our study, of whom 271 (30%) had isolated TBI. Only 35% of hospitalized patients with isolated TBI were defined as urgent by the ALS providers versus 67% in the non-isolated TBI group (P < 0.001). RESULTS: Overall, 29% of the TBIs in the non-isolated group were missed by the ALS providers vs. 11% in the isolated group. CONCLUSIONS: Concomitant injuries may delay the diagnosis of TBI by ALS providers. These findings should be considered in the prehospital evaluation to potentially improve the care and outcome of head injury patients.

Patterns in vehicle-ramming attacks.

BACKGROUND: Vehicle-ramming attacks have become a common tactic for terror organizations worldwide. However, the medical implications of vehicle-ramming attacks remain unknown. OBJECTIVES: To investigate the characteristics of vehicle-ramming attack incidents and casualties in order to assist in guiding the policy of medical organizations. METHODS: In this study we included all vehicle-ramming attacks recorded in the Israel Defense Forces-Trauma Registry between 2015 and 2019. Records were screened using text mining of incident, casualty, and injury descriptions. The selected records were examined manually to ensure that they were vehicle-ramming attacks. Incident and casualty data were retrieved from the trauma registry. RESULTS: During the years 2015-2019, a total of 36 vehicle-ramming attacks with 113 casualties were documented in the trauma registry. The median number of casualties, urgent casualties, and fatalities per incident was 3 (interquartile range [IQR] 2-5), 1 (IQR 1-2), and 1 (IQR 1-1), respectively. Of the incidents, 15 (42%) had three or more casualties. The most prevelant day of the week was Friday with 9 incidents (25%). Within the day, 21 incidents (58%) occurred between the hours of 12:00 and 18:00. Commonly injured body regions were lower extremities (55%), head (28%), and upper extremities. Ten victims (9%) died before arriving at a hospital. CONCLUSIONS: Vehicle-ramming attacks tend to have multiple casualties, be deadly, occur more often on Fridays and in the afternoon, and result mostly in injuries to the extremities and the head. These findings could guide policymaking to improve medical response to vehicle-ramming attacks.

Trends in prehospital pain management: two decades of point-of-injury care.

BACKGROUND: Pain control in trauma is an integral part of treatment in combat casualty care. More soldiers injured on the battlefield need analgesics for pain than life-saving interventions (LSIs). Early treatment of pain improves outcomes after injury, while inadequate treatment leads to higher rates of post-traumatic stress disorder (PTSD). OBJECTIVES: To describe the experience of the Israel Defense Forces (IDF) Medical Corps with prehospital use of analgesia. METHODS: All cases documented in the IDF-Trauma Registry between January 1997 and December 2019 were examined. Data collection included analgesia administered, mechanism of injury, wound distribution, and life-saving interventions performed. RESULTS: Of 16,117 patients, 1807 (11.2%) had at least one documented analgesia. Demographics included 91.2% male; median age 21 years. Leading mechanism of injury was penetrating (52.9%). Of injured body regions reported, 46.2% were lower extremity wounds. Most common types of analgesics were morphine (57.2%) and fentanyl (27%). Over the two decades of the study period, types of analgesics given by providers at point of injury (POI) had changed. Fentanyl was introduced in 2013, and by 2019 was given to 39% of patients. Another change was an increase of casualties receiving analgesia from 5-10% until 2010 to 34% by 2019. A total of 824 LSIs were performed on 556 patients (30.8%) receiving analgesia and no adverse events were found in any of the casualties. CONCLUSIONS: Most casualties at POI did not receive any analgesics. The most common analgesics administered were opioids. Over time analgesic administration has gained acceptance and become more commonplace on the battlefield.

A randomized, controlled, blinded evaluation of augmenting point-of-care ultrasound and remote telementored ultrasound in inexperienced operators.

BACKGROUND: Handheld ultrasound devices present an opportunity for prehospital sonographic assessment of trauma, even in the hands of novice operators commonly found in military, maritime, or other austere environments. However, the reliability of such point-of-care ultrasound (POCUS) examinations by novices is rightly questioned. A common strategy being examined to mitigate this reliability gap is remote mentoring by an expert. OBJECTIVES: To assess the feasibility of utilizing POCUS in the hands of novice military or civilian emergency medicine service (EMS) providers, with and without the use of telementoring. To assess the mitigating or exacerbating effect telementoring may have on operator stress. METHODS: Thirty-seven inexperienced physicians and EMTs serving as first responders in military or civilian EMS were randomized to receive or not receive telementoring during three POCUS trials: live model, Simbionix trainer, and jugular phantom. Salivary cortisol was obtained before and after the trial. Heart rate variability monitoring was performed throughout the trial. RESULTS: There were no significant differences in clinical performance between the two groups. Iatrogenic complications of jugular venous catheterization were reduced by 26% in the telementored group (P < 0.001). Salivary cortisol levels dropped by 39% (P < 0.001) in the telementored group. Heart rate variability data also suggested mitigation of stress. CONCLUSIONS: Telementoring of POCUS tasks was not found to improve performance by novices, but findings suggest that it may mitigate caregiver stress.

BladeShield 101: A Novel Prehospital Digital Wearable Combat Casualty Card.

BACKGROUND: The Israeli Defense Forces-Medical Corps (IDF-MC) focuses on reducing preventable death by improving prehospital trauma care. High quality documentation of care can serve casualty care and to improve future care. Currently, paper casualty cards are used for documentation. Incomplete data acquisition and inadequate data handover are common. To resolve these deficits, the IDF-MC launched the BladeShield 101 project. OBJECTIVES: To assess the quality of casualty care data acquired by comparing standard paper casualty cards with the BladeShield 101. METHODS: The BladeShield 101 system consists of three components: a patient unit that records vital signs and medical care provided, a medical sensor that transmits to the patient unit, and a ruggedized mobile device that allows providers to access and document information. We compared all trauma registries of casualties treated between September 2019 and June 2020. RESULTS: The system was applied during the study period on 24 patients. All data were transferred to the military trauma registry within one day, compared to 72% (141/194) with a paper casualty card (P < 0.01). Information regarding treatment time was available in 100% vs. 43% (P < 0.01) of cases and 98% vs. 67% (P < 0.01) of treatments provided were documented comparing BladeShield 101 with paper cards, respectively. CONCLUSIONS: Using an autonomous system to record, view, deliver, and store casualty information may resolve most current information flow deficits. This solution will ultimately significantly improve individual patient care and systematic learning and development processes.

The Influence of Gender Bias: Is Pain Management in the Field Affected by Health Care Provider's Gender?

INTRODUCTION: Appropriate pain management indicates the quality of casualty care in trauma. Gender bias in pain management focused so far on the patient. Studies regarding provider gender are scarce and have conflicting results, especially in the military and prehospital settings. STUDY OBJECTIVE: The purpose of this study is to investigate the effect of health care providers' gender on pain management approaches among prehospital trauma casualties treated by the Israel Defense Forces (IDF) medical teams. METHODS: This retrospective cohort study included all trauma casualties treated by IDF senior providers from 2015-2020. Casualties with a pain score of zero, age under 18 years, or treated with endotracheal intubation were excluded. Groups were divided according to the senior provider's gender: only females, males, or both female and male. A multivariate analysis was performed to assess the odds ratio of receiving an analgesic, depending on the presence of a female senior provider, adjusting for potential confounders. A subgroup analysis was performed for "delta-pain," defined as the difference in pain score during treatment. RESULTS: A total of 976 casualties were included, of whom 835 (85.6%) were male. Mean pain scores (SD) for the female only, male only, and both genders providers were 6.4 (SD = 2.9), 6.4 (SD = 3.0), and 6.9 (SD = 2.8), respectively (P = .257). There was no significant difference between females, males, or both female and male groups in analgesic treatment, overall and per specific agent. This remained true also in the multivariate model. Delta-pain difference between groups was also not significant. Less than two-thirds of casualties in this study were treated for pain among all study groups. CONCLUSION: This study found no association between IDF Medical Corps providers' gender and pain management in prehospital trauma patients. Further studies regarding disparities in acute pain treatment are advised.

The association between helicopter emergency medical services and early casualty survival: a nationwide study.

BACKGROUND: Helicopter emergency medical services (HEMS) allow for shorter transport duration in long-distance evacuations and facilitate advanced en-route medical care access. Studies comparing HEMS with ground emergency medical services (GEMS), including the outcome of prehospital mortality, are lacking. OBJECTIVE: This study aimed to evaluate the association between HEMS and early mortality in Israel. SETTING: A retrospective cohort study was conducted of the cross-referenced Israel Defense Forces Trauma Registry and Israel National Trauma Registry databases. OUTCOME MEASURES AND ANALYSIS: Univariable logistic regression was used to assess the association between HEMS and early mortality, defined as mortality within 1 day of the injury. Regression analysis was further performed stratifying by event type (military or civilian) or type of injury (penetrating or nonpenetrating). RESULTS: A total of 2344 casualties were included in the study, of whom 756 (32.3%) were evacuated by air. Early mortality rates were 90/1588 (5.7%) and 37/756 (4.9%) in GEMS and HEMS groups, respectively. Regression analysis found no significant analysis between HEMS and early mortality [OR, 0.86 (95% CI, 0.57-1.26)]. Stratified by event type, a nonsignificant association between HEMS and early mortality was demonstrated for combat [OR, 1.69 (95% CI, 0.79-3.92)] and noncombat [OR, 0.73 (95% CI, 0.4-1.25)] events. HEMS was associated with decreased early mortality among casualties with a penetrating injury [OR, 0.59 (95% CI, 0.34-0.98)] but not associated with early mortality among casualties with a nonpenetrating injury [OR, 0.84 (95% CI, 0.43-1.52)]. CONCLUSION: HEMS was not associated with a decrease in early mortality among trauma casualties in this study encompassing the prehospital and hospital scenes. There was a positive trend and a decrease in mortality from penetrating injuries. Further research to ascertain which casualties benefit from HEMS is warranted and will allow for more precise use of this expensive resource.

Predictors of mortality in COVID-19 patients treated with convalescent plasma therapy.

Several options to treat hospitalized severe COVID-19 patients have been suggested. The study aimed to describe survival in patients treated with convalescent COVID plasma (CCP) and to identify in-hospital mortality predictors. This prospective cohort study examined data from 112 severe COVID-19 patients hospitalized in the Corona Departments in an acute care hospital who received two units of CCP (at least one of them high-titer). Demographic and medical data was retrieved from the patients' electronic health records (EHR). Possible predictors for in-hospital mortality were analyzed in a univariate analysis and those found to be clinically significant were further analyzed in a multivariable analysis. Median age was 67 years (IQR 55-74) and 66 (58.9%) of them were males. Of them, 20 (17.9%) died in hospital. On multivariable analysis diabetes mellitus (p = 0.004, OR 91.54), mechanical ventilation (p = 0.001, OR 59.07) and lower albumin levels at treatment (p = 0.027, OR 0.74) were significantly associated with increased in-hospital mortality. In our study, in-hospital mortality in patients receiving CCP is similar to that reported for the general population, however certain variables mentioned above were associated with increased in-hospital mortality. In the literature, these variables were also associated with a worse outcome in patients with COVID-19 who did not receive CCP. As evidence points toward a benefit from CCP treatment in immunocompromised patients, we believe the above risk factors can further define COVID-19 patients at increased risk for mortality, enabling the selection of candidates for early treatment in an outpatient setting if possible.

Qualifying coronavirus disease 2019 convalescent plasma donors in Israel.

BACKGROUND AND OBJECTIVES: Passive immunization using investigational COVID-19 convalescent plasma (CCP) is a promising therapeutic strategy and could improve outcome if transfused early and contain high levels of anti-SARS-CoV-2 antibodies. We report the management of a national CCP collection and distribution program in Israel. MATERIALS AND METHODS: From 1 April 2020 to 15 January 2021, 4020 volunteer donors donated 5221 CCP units and 837 (20.8%) donors donated more than once. Anti-nucleocapsid IgG antibodies were determined using chemiluminescent immunoassay method (Abbott). A statistical model based on repeated IgG tests in sequential donations was created to predict the time of antibody decline below sample/cut-off (S/CO) level of 4.0. RESULTS: Ninety-six percent of CCP donors suffered a mild disease or were asymptomatic. Older donors had higher antibody levels. Higher antibody levels (S/CO ≥4) were detected in 35.2% of the donors. Low positive (S/CO ≥1.4-3.99) were found in 37%, and 27.8% had undetectable antibodies (S/CO ≤1.4). The model predicted decrease antibody thresholds of 0.55%/day since the first CCP donation, providing guidance for the effective timing of future collections from donors with high antibody levels. CONCLUSIONS: An efficient CCP collection and distribution program was achieved, based on performing initial and repeated plasma collections, preferably from donors with higher antibody levels, and only antibody-rich units were supplied for therapeutic use. The inventory met the quantity and quality standards of the authorities, enabled to respond to the growing demand of the medical system and provide a product that may contribute to improve prognosis in patients with COVID-19.

Prevalence of significant traumatic brain injury among patients intubated in the field due to impaired level of consciousness.

OBJECTIVE: Current guidelines advocate prehospital endotracheal intubation (ETI) in patients with suspected severe head injury and impaired level of consciousness. However, the ability to identify patients with traumatic brain injury (TBI) in the prehospital setting is limited and prehospital ETI carries a high complication rate. We investigated the prevalence of significant TBI among patients intubated in the field for that reason. METHODS: Data were retrospectively collected from emergency medical services and hospital records of trauma patients for whom prehospital ETI was attempted and who were transferred to Rambam Health Care Campus, Israel. The indication for ETI was extracted. The primary outcome was significant TBI (clinical or radiographic) among patients intubated due to suspected severe head trauma. RESULTS: In 57.3% (379/662) of the trauma patients, ETI was attempted due to impaired consciousness. 349 patients were included in the final analysis: 82.8% were male, the median age was 34 years (IQR 23.0-57.3), and 95.7% suffered blunt trauma. 253 patients (72.5%) had significant TBI. In a multivariable analysis, Glasgow Coma Scale>8 and alcohol intoxication were associated with a lower risk of TBI with OR of 0.26 (95% CI 0.13-0.51, p < 0.001) and 0.16 (95% CI 0.06-0.46, p < 0.001), respectively. CONCLUSION: Altered mental status in the setting of trauma is a major reason for prehospital ETI. Although most of these patients had TBI, one in four of them did not suffer a significant TBI. Patients with a higher field GCS and those suffering from intoxication have a higher risk of misdiagnosis. Future studies should explore better tools for prehospital assessment of TBI and ways to better define and characterize patients who may benefit from early ETI.

High Success Rate of Prehospital and En Route Cricothyroidotomy Performed in the Israel Defense Forces: 20 Years of Experience.

INTRODUCTION: Securing the airway is a crucial stage of trauma care. Cricothyroidotomy (CRIC) is often addressed as a salvage procedure in complicated cases or following a failed endotracheal intubation (ETI). Nevertheless, it is a very important skill in prehospital settings, such as on the battlefield. HYPOTHESIS/PROBLEM: This study aimed to review the Israel Defense Forces (IDF) experience with CRIC over the past two decades. METHODS: The IDF Trauma Registry (IDF-TR) holds data on all trauma casualties (civilian and military) cared for by military medical teams since 1997. Data of all casualties treated by IDF from 1998 through 2018 were extracted and analyzed to identify all patients who underwent CRIC procedures.Variables describing the incident scenario, patient's characteristics, injury pattern, treatment, and outcome were extracted. The success rate of the procedure was described, and selected variables were further analyzed and compared using the Fisher's-exact test to identify their effect on the success and failure rates. Odds Ratio (OR) was further calculated for the effect of different body part involvement on success and for the mortality after failed ETI. RESULTS: One hundred fifty-three casualties on which a CRIC attempt was made were identified from the IDF-TR records. The overall success rate of CRIC was reported at 88%. In patients who underwent one or two attempts, the success rate was 86%. No difference was found across providers (physician versus paramedic). The CRIC success rates for casualties with and without head trauma were 80% and 92%, respectively (P = .06). Overall mortality was 33%. CONCLUSIONS: This study shows that CRIC is of merit in airway management as it has shown to have consistently high success rates throughout different levels of training, injuries, and previous attempts with ETI. Care providers should be encouraged to retain and develop this skill as part of their tool box.

Impact of surfactant selection and incorporation on in situ nanoparticle formation from amorphous solid dispersions.

Spray dried amorphous solid dispersions (ASDs) stand as one of the most effective formulation strategies to address issues of low aqueous solubility when developing new chemical entities.An emerging research topic focusing on the formation of amorphous nanoparticles or nanodroplets from ASD formulations has attracted attention recently. These ASD nanoparticlescan be highly beneficial and able to further increase oral bioavailability. The incorporation of surfactants in ASD formulations has been shown to facilitate the formation of these nanoparticles. Therefore, understanding the mechanism of surfactant-promoted nanoparticle formation becomes critical for the rational design of ASD formulations. This work demonstrated the importance of inclusion of the surfactant within the ASD composition for nanoparticle formation. In contrast, when a surfactant is added externally (e.g., by inclusion in the dosing vehicle), only a limited degree of nanoparticle formation was observed even at the optimized surfactant-to-drug ratios. A variety of different surfactants were also assessed for understanding their impact on ASD nanoparticle formation. The spray drying systems containing nonionic surfactants, Tween 80 and Vitamin E TPGS, produced higher amounts of in situ ASD nanoparticles when compared to an anionic surfactant, sodium lauryl sulfate (SLS). The ASD nanoparticles produced by the Genentech developmental compound, GDC-0334, were highly stable and retained their original particle size and amorphous feature for at least 18 h under biorelevant conditions. The high degree of nanoparticle formation from spray dried GDC-0334 containing Tween 80 combined with the superior physical stability of the nanoparticles also translated to enhanced in vivo performance in a rat pharmacokinetics study.