Life-threatening Medical Emergency Research Articles

Severe acute alcoholic pancreatitis complicated by distributive shock, abdominal compartment syndrome, and black pleural effusion

Severe acute pancreatitis (SAP) is a life-threatening medical emergency that can lead to multi-system organ failure and mortality. Here, we highlight a case of SAP complicated by a black pleural effusion (BPE), distributive shock, and acute abdominal compartment syndrome (ACS) requiring emergent decompressive laparotomy. BPE fluid analysis was consistent with previously reported exudative effusions from a pancreatic pseudocyst, though the computed tomography (CT) of abdomen and pelvis did not show definitive evidence of a pseudocyst. In addition, black fluid was also discovered during decompressive laparotomy for ACS. It is possible that the severely elevated intra-abdominal pressure contributed to a temporary translocation/transudation of this fluid from the abdominal cavity into the pleural space, as no re-accumulation of the BPE was observed on a follow-up CT after thoracostomy tube removal.

Current Management of Acute Severe Ulcerative Colitis: New Insights on the Surgical Approaches

Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency with considerable morbidity. Despite recent advances in medical IBD therapy, colectomy rates for ASUC remain high. A scoping review of published articles on ASUC was performed. We collected data, such as general information of the disease, diagnosis and initial assessment, and available medical and surgical treatments focusing on technical aspects of surgical approaches. The most relevant articles were considered in this scoping review. The management of ASUC is challenging; currently, personalized treatment for it is unavailable. Sequential medical therapy should be administrated, preferably in high-volume IBD centers with close patient monitoring and indication for surgery in those cases with persistent symptoms despite medical treatment, complications, and clinical worsening. A total colectomy with end ileostomy is typically performed in the acute setting. Managing rectal stump is challenging, and all individual and technical aspects should be considered. Conversely, when performing elective colectomy for ASUC, a staged surgical procedure is usually preferred, thus optimizing the patients’ status preoperatively and minimizing postoperative complications. The minimally invasive approach should be selected whenever technically feasible. Robotic versus laparoscopic ileal pouch–anal anastomosis (IPAA) has shown similar outcomes in terms of safety and postoperative morbidity. The transanal approach to ileal pouch–anal anastomosis (Ta-IPAA) is a recent technique for creating an ileal pouch–anal anastomosis via a transanal route. Early experiences suggest comparable short- and medium-term functional results of the transanal technique to those of traditional approaches. However, there is a need for additional comparative outcomes data and a better understanding of the ideal training and implementation pathways for this procedure. This manuscript predominantly explores the surgical treatment of ASUC. Additionally, it provides an overview of currently available medical treatment options that the surgeon should reasonably consider in a multidisciplinary setting.

Efficacy of empirical Ciprofloxacin or Cefixime plus Metronidazole therapy for the treatment of liver abscess: a randomized control clinical trial

Liver abscess is a potentially life-threatening medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage is therapeutic. The rational for using empirical intravenous broad-spectrum antimicrobials upfront instead of oral Fluoroquinolone or Cephalosporin is contentious. In this double blind randomized control clinical trial 69 participants received Ciprofloxacin (500 mg q 12 hourly) and 71 participants received Cefixime (200 mg q 12 hourly) orally for 2 weeks. Both the group received oral Metronidazole (800 mg q 8 hourly) for 2 weeks and percutaneous drainage or aspiration of the abscess was done as per indication and followed-up for 8 weeks. Out of 140 participants, 89.3% (N = 125) achieved clinical cure, 59 (85.5%) in Ciprofloxacin group and 66 (93%) in Cefixime group (p = 0.154). Mean duration of antimicrobial therapy was 16.2 ± 4.3 days, 15.1 ± 4.5 days in Ciprofloxacin group and 16.0 ± 4.2 days in Cefixime group (p = 0.223). Total 15 (10.7%) participants had treatment failure, 10 (14.5%) in Ciprofloxacin group and 5 (7.0%) in Cefixime group (p = 0.154). The most common reason for treatment failure was need of prolong (> 4 weeks) antimicrobial therapy due to persistent hepatic collection requiring drainage, which was significantly (p = 0.036) higher in Ciprofloxacin (14.5%, N = 10) group, compared to the Cefixime (4.2%, N = 3) group. In conclusion, both, the Ciprofloxacin or Cefixime plus Metronidazole for duration of 2–3 weeks were efficacious as empirical oral antimicrobial regimen along with prompt percutaneous drainage or aspiration for the treatment of uncomplicated liver abscess with similar efficacy. Oral Cefixime was better than Ciprofloxacin in term of lesser chance of treatment failure due to persistent collection which is required to be investigated further in larger clinical trial.Trial registration: clinicaltrials.gov PRS ID: NCT03969758, 31/05/2019.

Chronic basilar artery occlusion: a retrospective monocentric study.

Acute basilar artery occlusion is a life-threatening medical emergency with a highly elevated mortality rate when left untreated. Little is known about symptoms and clinical progression of chronic occlusions. The aim of this study was to systematically analyze the clinical presentation of patients with chronic basilar artery occlusion (CBAO). Monocentric retrospective analysis of adult patients with CBAO was treated between 2015 and 2023 in the Department of Neurology, Klinikum Kassel. Inclusion criteria were basilar artery occlusion without brainstem infarction as well as patients with a basilar artery occlusion in whom revascularization could not be achieved and a follow-up period of at least 3months. A total of 15 patients were found. In five patients basilar artery occlusion was diagnosed as an incidental finding, four patients had neurological symptoms but no proven brainstem infarction (3 × transient ischemic attack, 1 × isolated posterior artery infarct) and six patients presented with acute basilar artery occlusion and a follow-up > 3months. The most common site of occlusion was midbasilar (80%, n = 12), isolated (n = 7) or in combination with other locations (n = 5). In all cases collateralization could be demonstrated by the posterior communicatingarteries. The most common vascular risk factors (VRF) were hypertension (100%) and hypercholesterolemia (67%). Patients with CBAO may present with only mild symptoms or may even be asymptomatic. This condition may be survived for a long time. The high percentage of vascular risk factors and further cerebral vessel occlusions suggest arteriosclerosis as the major causing factor of CBAO.

Medical malpractice and epidural hematomas: a retrospective analysis of 101 cases in the United States.

Neurosurgeons face particularly high rates of litigation compared to physicians in other fields. Malpractice claims are commonly seen after mismanagement of life-threatening medical emergencies, such as epidural haematomas. Due to the lack of legal analysis pertaining to this condition, the aim of this study is to identify risk factors associated with litigation in cases relating to the diagnosis and treatment of epidural haematomas. Westlaw Edge, an online database, was used to analyze malpractice cases related to epidural haematomas between 1986 and 2022. Information regarding plaintiff demographics, defendant specialty, reason for litigation, trial outcomes, and payouts for verdicts and settlements were recorded. Comparative analysis between cases that returned a jury verdict in favour of the plaintiff versus defendant was completed. A total of 101 cases were included in the analysis. Failure to diagnose was the most common reason for litigation (n = 64, 63.4%), followed by negligent care resulting in an epidural haematoma (n = 44, 43.6%). Spine surgery (n = 29, 28.7%), trauma (n = 28, 27.7%), and epidural injection/catheter/electrode placement (n = 21, 20.8%) were the primary causes of haematomas. Neurosurgeons (n = 18, 17.8%) and anesthesiologists (n = 17, 16.8%) were the two most common physician specialties cited as defendants. Most cases resulted in a jury verdict in favour of the defense (n = 54, 53.5%). For cases ending in plaintiff verdicts, the average payout was $3621590.45, while the average payment for settlements was $2432272.73. Failure to diagnose epidural haematomas is the most common reason for malpractice litigation, with neurosurgeons and anesthesiologists being the most common physician specialties to be named as defendants. More than half of all cases returned a jury verdict in favour of the defense and, on average, settlements proved to be more cost-effective than plaintiff verdicts.

Differences in In-Hospital and Follow-Up Outcomes Between Non-A Non-B Aortic Dissection and Type B Aortic Dissection Treated by Endovascular Based Treatment.

Non-A non-B aortic dissection (AD) is a rare and life-threatening medical emergency, and it has been controversial whether it should be managed as type B aortic dissection (TBAD). The study aims to compare in-hospital and follow-up outcomes between patients with non-A non-B AD and those with TBAD treated by endovascular based treatment (EBT). From January 2017 to December 2021, 96 consecutive patients with non-A non-B AD met the inclusion criteria and underwent EBT. Patients with TBAD were matched to patients with non-A non-B AD at a 1:1 ratio using propensity score matching analysis to correct for baseline confounding factors. The primary endpoint was all-cause mortality. Aortic-related events were defined as dissection-related death, aortic rupture, retrograde type A aortic dissection, reintervention, and type Ia endoleak. Patients with non-A non-B AD required more TEVAR-related adjunctive procedures compared to TBAD patients during EBT and they required a longer ICU length of stay (36.0 vs 24.0 hours, P < .05) as well as a longer hospitalization (8.0 vs 7.0 days, P < .05) after EBT. There was no statistical difference in overall survival after EBT for patients with TBAD and non-A non-B AD. However, compared to patients with TBAD, non-A non-B AD patients had a higher rate of reintervention and experienced more aortic-related late events during follow-up. Patients with non-A non-B acute AD who are treated with EBT do not have higher in-hospital or follow-up mortality rates compared to patients with type B AD. However, there is an increased risk of reintervention and aortic-related late events after the intervention during follow-up.

ECMO for drug-refractory electrical storm without a reversible trigger: a retrospective multicentric observational study.

Drug-refractory electrical storm (ES) is a life-threatening medical emergency. We describe the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in drug-refractory ES without a reversible trigger, for which specific guideline recommendations are still lacking. Retrospective observational study in four Iberian centres on the indications, treatment, complications, and outcome of drug-refractory ES not associated with acute coronary syndromes, decompensated heart failure, drug toxicity, electrolyte disturbances, endocrine emergencies, concomitant acute illness with fever, or poor compliance with anti-arrhythmic drugs, requiring VA-ECMO for circulatory support. Thirty-four (6%) out of 552 patients with VA-ECMO for cardiogenic shock were included [71% men; 57 (44-62) years], 65% underwent cardiopulmonary resuscitation before VA-ECMO implantation, and 26% during cannulation. Left ventricular unloading during VA-ECMO was used in 8 (24%) patients: 3 (9%) with intraaortic balloon pump, 3 (9%) with LV vent, and 2 (6%) with Impella. Thirty (88%) had structural heart disease and 8 (24%) had an implantable cardioverter-defibrillator. The drug-refractory ES was mostly due to monomorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) (59%), isolated monomorphic VT (26%), polymorphic VT (9%), or VF (6%). Thirty-one (91%) required deep sedation, 44% overdrive pacing, 36% catheter ablation, and 26% acute autonomic modulation. The main complications were nosocomial infection (47%), bleeding (24%), and limb ischaemia (21%). Eighteen (53%) were weaned from VA-ECMO, and 29% had heart transplantation. Twenty-seven (79%) survived to hospital discharge (48 (33-82) days). Non-survivors were older [62 (58-67) vs. 54 (43-58); P<0.01] and had a higher first rhythm disorder-to-ECMO interval [0 (0-2) vs. 2 (1-11) days; P=0.02]. Seven (20%) had rehospitalization during follow-up [29 (12-48) months], with ES recurrence in 6%. VA-ECMO bridged drug-refractory ES without a reversible trigger with a high success rate. This required prolonged hospital stays and coordination between the ECMO centre, the electrophysiology laboratory, and the heart transplant programme.

Blood Urea Nitrogen to Serum Albumin Ratio as A New Prognostic Indicator in Critically Ill Patients with Diabetic Ketoacidosis: A Retrospective Cohort Study.

To investigate the predictive value of the blood urea nitrogen to serum albumin ratio for in-hospital and out-of-hospital mortality in critically ill patients with diabetic ketoacidosis. Data were obtained from the Medical Information Mart for Intensive Care III (MIMIC III) database, and all eligible participants were categorized into two groups based on the BAR cutoff value. Multiple logistic regression analysis was conducted to determine the association between BAR and in-hospital mortality. The Kaplan-Meier (K-M) analysis was performed to evaluate the predictive performance of BAR. Propensity score matching (PSM) was applied to control confounding factors between the low and high BAR groups. A total of 589 critically ill patients with diabetic ketoacidosis were enrolled. Patients with diabetic ketoacidosis with a higher BAR level were associated with higher in- and out-hospital mortality (all p<0.001). A significant 4-year survival difference was observed between the low and high BAR groups (p<0.0001). After PSM analysis, two PSM groups (202 pairs, n=404) were generated, and similar results were observed in the K-M curve (p<0.0001). Elevated BAR levels were associated with an increased risk of in-hospital mortality in critically ill patients with diabetic ketoacidosis, and BAR could serve as an independent prognostic factor in in-hospital and out-of-hospital mortality for patients diagnosed with diabetic ketoacidosis.

Small-molecule caspase-1 inhibitor CZL80 terminates refractory status epilepticus via inhibition of glutamatergic transmission.

Status epilepticus (SE), a serious and often life-threatening medical emergency, is characterized by abnormally prolonged seizures. It is not effectively managed by present first-line anti-seizure medications and could readily develop into drug resistance without timely treatment. In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase-1-/- mice but partially terminated SE in IL1R1-/- mice, suggesting the SE termination effect of CZL80 was dependent on the caspase-1, but not entirely through the downstream IL-1β pathway. Furthermore, in vivo calcium fiber photometry revealed that CZL80 completely reversed the neuroinflammation-augmented glutamatergic transmission in SE. Together, our results demonstrate that caspase-1 inhibitor CZL80 terminates diazepam-resistant SE by blocking glutamatergic transmission. This may be of great therapeutic significance for the clinical treatment of refractory SE.

Should we operate on patients with acute type A aortic dissection who present with cardiopulmonary resuscitation?

Acute aortic dissection type A (AADA) is a life-threatening medical emergency. Emergent surgical repair is the gold standard but mortality remains high. Mortality is even higher in patients who arrive at the hospital in poor condition, especially after cardiopulmonary resuscitation (CPR). This study was designed to analyse the outcome of patients who underwent surgery for AADA and who require preoperative CPR. Between 2000 and 2023, 810 patients underwent emergent surgery for AADA at our centre. Of these, 63 had preoperative CPR. We performed a retrospective analysis with follow-up. Mean age was 64 ± 13 years and 37 (59%) patients were male. Further, 50 (79%) patients had preoperative intubation, and 54 (86%) had pericardial effusion. Twenty-four (38%) patients had out-of-hospital CPR, 19 (30%) required CPR in hospital and 20 (32%) needed CPR in the operating room. Successful CPR with return of spontaneous circulation was achieved in 41 (65%) patients, and 22 (35%) underwent emergent surgery under ongoing CPR. The median time of CPR was 10 (interquartile range 12) min, and the median time from onset of symptoms to start of the operation was 5.5 (interquartile range 4.8) h. The majority of patients underwent ascending aortic replacement with hemiarch repair (n = 37, 59%). Further, 26 (41%) patients underwent full root replacement. Another 15 (24%) patients underwent total arch repair with or without (frozen) elephant trunk repair. Postoperative stroke was present in 8 (13%) patients. The 30-day mortality was 29 (46%). The 30-day mortality of patients with preoperative intubation was not significantly higher (n = 15/28, 54%, P = 0.446). The 1-, 5- and 10-year survival rates of the entire group were 42, 39 and 36%. Early mortality for patients undergoing surgery for AADA with preoperative CPR is extremely high (almost 50%). However, this means that also ∼50% of patients benefit from surgery despite poor preoperative prognosis. Patients with preoperative intubation after CPR and unknown neurological condition should also undergo surgery. Patients who survive the initial operation for AADA have acceptable long-term survival. Emergent surgery should be offered for all patients with AADA regardless of the preoperative condition, even after CPR.

A137 BALLOON-ASSISTED ENDOSCOPY FOR SMALL BOWEL BLEEDING – A REVIEW

Abstract Background Gastrointestinal (GI) bleeding is a potentially life-threatening medical emergency requiring immediate medical attention. Obscure GI bleeding (OGIB) Is defined as GI bleeding with no obvious culprit lesion found on initial upper or lower endoscopy. Further investigations are needed as 75% of those cases originate in the small bowel. The advent of small bowel endoscopy, consisting of video capsule endoscopy (VCE) and device-assisted enteroscopy (DAE) has allowed clinicians to endoscopically visualize the entire GI tract and perform therapeutic interventions. These devices include balloon assisted endoscopy (BAE) and Spiral Endoscopy (SPE). Aims The objectives of this review are to analyze the definitions, etiologies, and risk factors of OGIB. Furthermore, we reviewed the diagnostic and therapeutic yields of DAE and its safety profile. Due to the adverse effects and recall of SPE, we only report here on BAE. Methods A literature review was conducted using PubMed and OvidSP (Medline) to identify articles on the use of VCE and DAE for OGIB. Keywords included a combination of gastrointestinal bleeding with occult, obscure, active and inactive, small bowel bleed, diagnostic yield, therapeutic yield, and rebleeding rate. The information was obtained via systematic review and meta-analysis, retrospective studies, and case reports. Results A total of 32 papers were reviewed. The most common causes of OGIB reported were vascular lesions (23-47%), inflammatory lesions (12-16%), and tumors (5-16%). The risk factors associated with OGIB include age, cardiac disease, liver cirrhosis, chronic kidney disease, and hereditary vascular diseases. The overall diagnostic and therapeutic yields of BAE in OGIB were 76.3% and 49.5%, respectively. Factors that increased the yield included performing an initial VCE (increase by 7%) and performing the procedure within the first 10 days after the initial bleeding episode (87.5%) as compared to after 10 days (11.1%). Recurrent bleeding can occur in up to 46% of patients. Risk factors for rebleeding include cirrhosis, overt bleeding symptoms, and presence of multiple vascular lesions. Associated adverse effects in DAE were minor in 9.1% of patients and severe in less than 2%. These include bleeding (0.8%), perforation (0.3%), and pancreatitis (0.3%). Conclusions OGIB is a challenging clinical entity. BAE now allows clinicians to diagnose and treat culprit lesions in the small bowel with reasonable success and a strong safety profile, however timing and prior VCE can further optimize this. Clinical decisions and follow up should be made based around existing risk stratification tools and scores. Further prospective research is needed to determine optimal timing of DAE from presentation of OGIB that would increase diagnostic and therapeutic yields. Figure 1. A and B) Endoscopic images of small bowel vascular lesion. C) Bleeding vascular lesion treated with hemostatic clips. Funding Agencies None

Challenges with Life-Threatening Injuries in the Room of Reanimation.

Introduction: Patients with life-threatening injuries are a significant concern in the emergency department (ED). These injured people require timely care, as their lives depend on it, and a longer wait can result in organ failure, irreversible damage, and poor survival outcomes.&#x0D; The purpose of this research is the evaluation, epidemiology, management, diagnosis, treatment, systematization, and the results obtained for the injured in life-threatening cases with trauma, reducing morbidity, disability, and mortality while increasing survival.&#x0D; Material and Methods. In this retrospective study, we researched and analyzed the data of patients with critical traumatic injuries in DE treated from January-December 2021&#x0D; Results. During the study period, we analyzed 75,899 ED patients. Of these, 627 cases, or 0.83%, were severely injured and traumatically admitted as a life-threatening traumatic medical emergency in the resuscitation room. Attacked age were males 507 cases or 80.87% and females 120 cases 19.13% and over 16 were 46 cases or 6.67%. The main problem in the admission of the sick was the injured with disorders of consciousness, shock, cardiac, and respiratory failure, as well as issues at the systemic level.&#x0D; Conclusion. During the study period, we analyzed 75,899 ED patients. Of these, 627 cases, or 0.83%, were severely injured and traumatically admitted as a life-threatening traumatic medical emergency in the resuscitation room. Attacked age were males 507 cases or 80.87% and females 120 cases 19.13% and over 16 were 46 cases or 6.67%. The main problem in the admission of the sick was the injured with disorders of consciousness, shock, cardiac, and respiratory failure, as well as issues at the systemic level.&#x0D; Also, these critically injured require structured and well-organized care in the DE in the resuscitation room, with educated medical staff, nurses, and support staff trained with the mandatory BLS, BTLS, PHTLS, and ATLS courses, implementing and developing the algorithms standardized for structured care of the critically injured.&#x0D; Keywords: DE, traumatic, life-threatening medical emergency, CPR. monitoring, management,&#x0D;

Statistical evidence of mediastinitis in oromaxillofacial surgery

Inflammatory processes of the oromaxillofacial area remain a life-threatening medical and surgical emergency. One of the most severe complications associated with life-threatening OMF area infections is descending mediastinitis. Mediastinitis has an important place in the structure of oro-maxillofacial pathology both by its fulminant progression and the intensity of its manifestations. Mediastinitis in the OMF area occurs in the form of a strong inflammatory response of the mediastinal connective tissue as a result of the action of polymicrobial infection, with an increasing incidence and an equally high lethality of 70-80%. As one of the morbidity causes of OMF pathologies, with decreased immunity and work capacity of patients, polyvisceral damage coupled with septic shock, mediastinitis results in a significant impact on patients’ quality of life.

Quantifying Microvascular Structure in Healthy and Infarcted Rat Hearts Using Optical Coherence Tomography Angiography.

Myocardial infarction (MI) is a life-threatening medical emergency resulting in coronary microvascular dysregulation and heart muscle damage. One of the primary characteristics of MI is capillary loss, which plays a significant role in the progression of this cardiovascular condition. In this study, we utilized optical coherence tomography angiography (OCTA) to image coronary microcirculation in fixed rat hearts, aiming to analyze coronary microvascular impairment post-infarction. Various angiographic metrics are presented to quantify vascular features, including the vessel area density, vessel complexity index, vessel tortuosity index, and flow impairment. Pathological differences identified from OCTA analysis are corroborated with histological analysis. The quantitative assessments reveal a significant decrease in microvascular density in the capillary-sized vessels and an enlargement for the arteriole/venule-sized vessels. Further, microvascular tortuosity and complexity exhibit an increase after myocardial infarction. The results underscore the feasibility of using OCTA to offer qualitative microvascular details and quantitative metrics, providing insights into coronary vascular network remodeling during disease progression and response to therapy.

Immune-Checkpoint Inhibitors-Induced Type 1 Diabetes Mellitus: From Its Molecular Mechanisms to Clinical Practice.

With the increasing use of immune-checkpoint inhibitors (ICIs), such as anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and anti-programmed cell death-1 (PD-1), for the treatment of malignancies, cases of ICI-induced type 1 diabetes mellitus (ICI-T1DM) have been reported globally. This review focuses on the features and pathogenesis of this disease. T1DM is an immune-related adverse event that occurs following the administration of anti-PD-1 or anti-programmed death ligand-1 (PDL1) alone or in combination with anti-CTLA-4. More than half of the reported cases presented as abrupt-onset diabetic ketoacidosis. The primary mechanism of ICI-T1DM is T-cell stimulation, which results from the loss of interaction between PD-1 and PD-L1 in pancreatic islet. The similarities and differences between ICI-T1DM and classical T1DM may provide insights into this disease entity. ICI-T1DM is a rare but often life-threatening medical emergency that healthcare professionals and patients need to be aware of. Early detection of and screening for this disease is imperative. At present, the only known treatment for ICI-T1DM is insulin injection. Further research into the mechanisms and risk factors associated with ICI-T1DM development may contribute to a better understanding of this disease entity and the identification of possible preventive strategies.

ADDovenom: Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming.

Snakebite envenoming can be a life-threatening medical emergency that requires prompt medical intervention to neutralise the effects of venom toxins. Each year up to 138,000 people die from snakebites and threefold more victims suffer life-altering disabilities. The current treatment of snakebite relies solely on antivenom-polyclonal antibodies isolated from the plasma of hyperimmunised animals-which is associated with numerous deficiencies. The ADDovenom project seeks to deliver a novel snakebite therapy, through the use of an innovative protein-based scaffold as a next-generation antivenom. The ADDomer is a megadalton-sized, thermostable synthetic nanoparticle derived from the adenovirus penton base protein; it has 60 high-avidity binding sites to neutralise venom toxins. Here, we outline our experimental strategies to achieve this goal using state-of-the-art protein engineering, expression technology and mass spectrometry, as well as in vitro and in vivo venom neutralisation assays. We anticipate that the approaches described here will produce antivenom with unparalleled efficacy, safety and affordability.

Public Awareness and Knowledge of Sepsis: A Cross-Sectional Survey of Adults in the Western Region of Saudi Arabia.

Sepsis is a condition in which the body responds improperly to harmful microorganisms and infections, which triggers a chain reaction throughout the body. It is a life-threatening medical emergency. Infections that lead to sepsis, in most cases, start in the lungs, urinary tract, skin, or gastrointestinal tract. Without timely treatment, sepsis rapidly leads to multi-organ failure and death. The risk factors for sepsis include a weakened immune system, being 65 years of age or older, and chronic medical conditions including diabetes, lung disease, and kidney disease. A thorough understanding of the warning signs and symptoms, as well as prompt medical attention, are required for successful sepsis management. Early detection, antimicrobial therapy, and intensive supportive care are the cornerstones of the best sepsis management. This study aimed to assess the public awareness and knowledge of sepsis in the Western region of Saudi Arabia. This was a cross-sectional study conducted from the beginning of June till the end of August 2023, among 425 Saudi adults in the Western region above the age of 18 years. Data collection was carried out by administering a questionnaire through an online platform. The questionnaire included demographic information, risk factors, symptoms, protective factors, and the source of information about sepsis. The data collected were reviewed, coded, and then fed into IBM SPSS Statistics software for Windows, Version 21 (released 2012; IBM Corp., Armonk, NY). The study found that almost half (47.8%) of participants were aware of bacterial septicemia, with the most common sources of awareness being the internet (48.3%) and healthcare professionals (47.8%). Low immunity (75.9%) and infection (39.4%) have been the most frequently reported risk factors. Fever (31.5%) was the most commonly reported symptom. Participants from Yanbu and Jeddah and those in the healthcare sector had significantly higher awareness levels. The majority of participants (93.1%) had poor knowledge about the risk factors and symptoms of septicemia, with only 3.4% having fair or good knowledge. Sociodemographic characteristics did not significantly affect knowledge about septicemia (P>0.05). In summary, this study reveals that while awareness of bacterial septicemia is relatively high among the sample population, knowledge about the risk factors and symptoms of the condition is low. The internet, healthcare professionals, and social media play significant roles in raising awareness about bacterial septicemia. Participants from Yanbu and Jeddah, students, and healthcare sector workers had higher awareness levels compared to other groups. However, overall knowledge levels regarding bacterial septicemia were poor across various demographic characteristics. This highlights the need for targeted educational interventions to improve knowledge and understanding of septicemia and its risk factors and symptoms among the general population. Further research is needed to identify the reasons for low knowledge levels and develop effective strategies to improve awareness about bacterial septicemia.

Abstract 13229: Coiled-Coil Domain-Containing Protein 80 Protects Against Aortic Dissection by Maintaining the Contractile Smooth Muscle Cell Phenotype

Background: Aortic dissection (AD) is a life-threatening medical emergency characterized by adverse vascular remodeling. Effective prevention and treatment options are lacking for AD. Coiled-coil domain-containing protein 80 (CCDC80) plays an essential role in regulating vascular remodeling. In the present study, we aimed to define the role of CCDC80 in the formation and development of AD. Methods: The expression and subcellular localization of CCDC80 were determined in human and mouse AD. CCDC80 knockout mice (CCDC80 –/– ) and vascular smooth muscle cell (VSMC)-specific CCDC80 knockout mice (CCDC80 fl/fl SM22α Cre + ) were treated with angiotensin II (Ang II) or Ang II combined with β-aminopropionitrile monofumarate (BAPN) to induce AD models. RNA-Seq analysis combined with immunoprecipitation and blockage of the JAK2/STAT3 signaling pathway in CCDC80 –/– mice were used to evaluate the effect of CCDC80 deficiency on this pathway. Results: CCDC80 was downregulated in VSMCs in human and mouse AD. CCDC80 – / – mice challenged with Ang II and BAPN developed AD with higher frequency and severity compared with their littermate controls (66.7% vs. 100%, p &lt; 0.05). Remarkably, compared with littermate controls treated with Ang II, CCDC80 –/– mice (8.3% vs. 87.5%, p &lt; 0.05) and CCDC80 fl/fl SM22α Cre + mice (12.5% vs. 80%, p &lt; 0.05) frequently developed AD with severe elastin fragmentation and collagen deposition. CCDC80 interacted with JAK2; CCDC80 deficiency could promote VSMC phenotype switching, proliferation, and migration as well as matrix metalloproteinase production by activating the JAK2/STAT3 signaling pathway. The JAK2/STAT3 pathway-specific inhibitor ameliorated adverse vascular remodeling and reduced AD formation (90% vs. 55%, p &lt; 0.05) in CCDC80 knockout mice. Conclusion: CCDC80 deficiency exacerbates the progression of AD by activating the JAK2/STAT3 pathway involved in regulating the phenotype switching and function of VSMCs. Our findings suggest that CCDC80 is a potential target for the prevention and treatment of AD.

Facilitators and barriers of appropriate and timely initiation of intravenous fluids in patients with sepsis in emergency departments: a consensus development Delphi study

BackgroundSepsis is a life-threatening medical emergency in which appropriate and timely administration of intravenous fluids to patients with features of hypotension is critical to prevent multi-organ failure and subsequent death. However, compliance with recommended fluid administration is reported to be poor. There is a lack of consensus among emergency clinicians on some of the determinant factors influencing fluid administration in sepsis. Thus, the aim of this study was to identify the level of consensus among key stakeholders in emergency departments regarding the facilitators, barriers, and strategies to improve fluid administration.MethodsThe modified Delphi questionnaire with 23 statements exploring barriers, facilitators, and strategies to improve fluid administration was developed from the integration of findings from previous phases of the study involving emergency department clinicians. A two-round modified Delphi survey was conducted among key stakeholders with managerial, educational, supervision and leadership responsibilities using a “Reactive Delphi technique” from March 2023 to June 2023. The statements were rated for importance on a 9-point Likert scale. The RAND/UCLA Appropriateness Method (RAM) was used to identify the level of consensus (agreement/disagreement).ResultsOf the 21 panellists who completed Round 1 survey, 18 (86%) also completed Round 2. The panellists rated 9 out of 10 (90%) barriers, 3 out of 4 (75%) facilitators and all 9 (100%) improvement strategies as important. Out of the total 23 statements, 18 (78%) had agreement among the panellists. Incomplete vital signs at triage (Median = 9, IQR 7.25 to 9.00) as a barrier, awareness of importance of fluid administration in sepsis (Median = 9, IQR 8.00 to 9.00) as facilitator and provision of nurse-initiated intravenous fluids (Median = 9, IQR 8.00 to 9.00) as an improvement strategy were the highest rated statements.ConclusionThis is the first Delphi study identifying consensus on facilitators, barriers, and strategies to specifically improve intravenous fluid administration in sepsis in Australia. We identified 18 consensus-based factors associated with appropriate and timely administration of intravenous fluids in sepsis. This study offers empirical evidence to support the implementation of the identified strategies to improve patient outcomes.

Diabetic Ketoacidosis (DKA): A Severe Diabetes Mellitus Disorder

Diabetic ketoacidosis (DKA) is a life-threatening medical emergency that requires immediate evaluation and treatment. It remains a significant complication of diabetes and is increasing alarmingly worldwide. It is an endocrine complication that involves hyperglycemia, anion gap metabolic acidosis, and ketosis. It is characterized by hyperglycaemia with glucose is greater than 11 mmol/l (200 mg/dl), capillary/venous pH is less than 7.3, bicarbonate (HCO3–) is less than 15 mEq/l, serum anion gap is greater than 16 mmol/l, moderate to severe dehydration is seen and creatinine ratio is increased, and ketones (ketonemia and ketonuria ≥3 mmol/l) are present. It occurs in patients with type 1 diabetes (T1D), and type 2 diabetes (T2D); and early diagnosis, monitoring, and treatment are necessary for the welfare of the patients. Treatment of DKA involves volume expansion, insulin replacement, and prevention of hypokalemia. DKA can be prevented through the earlier recognition and initiation of insulin therapy. An attempt has been taken here to discuss the aspects of DKA in some detail.