Severe Shock Research Articles

Assessment of the Relationship between Adverse Allergic Transfusion Reaction and Serum IgE Level

Background: Allergic transfusion reactions (ATRs) are common adverse events during blood transfusions, ranging from mild urticaria to severe anaphylactic shock. Elevated serum immunoglobulin E (IgE) levels are known to mediate these reactions. This study aimed to assess the relationship between serum IgE levels and the Presence of ATRs in patients receiving fresh frozen plasma (FFP) transfusions. Methods: A cross-sectional observational study was conducted at the Department of Transfusion Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, from March 2019 to August 2021. The study included 55 patients aged 5-60 years who received FFP transfusions. Demographic data, clinical symptoms, and IgE levels were recorded. Data were analyzed using SPSS version 26, with statistical significance set at p<0.05. Result: The majority of participants were males (94.55%) and aged 11-20 years (45.45%). Most patients (85.45%) received multiple units of FFP. Clinical symptoms included itching (56.36%), urticarial rash (29.09%), vomiting (7.27%), and hypotension (7.27%). Raised IgE levels were found in 52.73% of participants, and a significant association was observed between elevated IgE levels and the presence of allergic reactions (p<0.01). Patients with allergic reactions had significantly higher mean IgE levels (521.4±434.6 IU/mL) compared to those without allergic reactions (67.8±33.2 IU/mL). Conclusion: Elevated serum IgE levels are significantly associated with the Presence of ATRs in patients receiving FFP transfusions. Monitoring IgE levels can help predict and manage allergic reactions, thereby improving transfusion safety and patient outcomes.

Shenfu injection alleviate gut ischemia/reperfusion injury after severe hemorrhagic shock through improving intestinal microcirculation in rats

BackgroundShenfu (SF) injection, a traditional Chinese medication, would improve microcirculation in cardiogenic shock and infectious shock. This study was aimed to explore the therapeutic potential of the SF injection in gut ischemia-reperfusion (I/R) injury after severe hemorrhagic shock (SHS) and resuscitation. Furthermore, we also investigated the optimal adm？ inistration timing. MethodsTwenty-four male SD rats were randomly divided into four groups: Sham group (sham, n = 6), Control group (n = 6), SF injection group (SF, n = 6), and Delayed Shenfu injection administration group (SF-delay, n = 6). In SHS and resuscitation model, rats were induced by blood draw to a mean arterial pressure (MAP) of 40 ± 5 mmHg within 1 h and then maintained for 40 min; HR, MAP ‘were recorded, microcirculation index [De Backer score, perfused small vessel density (PSVD), total vessel density (TVD), microcirculation flow index score (MFI), flow heterogeneity index (HI)] were analyzed. The blood gas index was detected, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), diamine oxidase (DAO), malondialdehyde (MDA) were measured by ELISA; ZO-1, and claudin-1 were measured by Western blotting. In addition, hematoxylin-eosin (HE) and periodic acid schiff (PAS) staining pathological sections of the intestinal mucosal tissues were also performed. ResultsSF injection increased the MAP, relieved the metabolic acidosis degree associated with the hypoperfusion, and improved the intestinal microcirculatory density and perfusion quality after I/R injury. The expression of DAO, MDA in intestinal tissue, and plasma IL-6, TNF-α significantly decreased in the SF injection group compared to the control group. The concentration of ZO-1 and claudin-1 is also higher in the SF injection group. In addition, the HE and PAS staining results also showed that SF injection could decrease mucosal damage and maintain the structure. In the SF-delay group, the degree of intestinal tissue damage was intermediate between that of the control group and SF injection group. ConclusionsSF injection protect the intestine from I/R injury induced by SHS and resuscitation, the mechanism of which might be through improving intestinal microcirculation, reducing the excessive release of inflammatory factors and increasing intestinal mucosal permeability. Furthermore, the protection effect is more pronounced if administration during the initial resuscitation phase.

#2545 Hemodialysis for salbutamol intoxication: patient case report

Abstract Background and Aims Salbutamol/albuterol is a moderately selective beta-2-adrenergic receptor agonist that acts as an airway smooth muscle relaxant. It is used to prevent and treat acute bronchospasm in various respiratory conditions. Due to its large volume of distribution, it is not considered dialysable. Method This is a clinical case report of inadvertent parenteral administration of salbutamol resulting in acute intoxication. Salvage renal replacement therapy was implemented due to the severity of the patient's clinical condition and the large amount of salbutamol administered. Multiple plasma measurements of salbutamol were taken during hemodialysis, allowing for a correlation to be made with the patient's clinical presentation. Results This case report presents an elderly patient with sepsis, Down syndrome, and liver cirrhosis. The patient required non-invasive ventilation due to worsening respiratory failure and was prescribed intravenous methylprednisolone. However, the patient inadvertently received 5mg of parenteral salbutamol (albuterol), which resulted in immediate severe arrhythmic tachycardia followed by hemodynamic collapse. After unsuccessful cardioversion and treatment with landiolol infusion, salvage hemodialysis was initiated to reduce the suspected highly elevated serum salbutamol levels. After 30 minutes, sinus rhythm with normocardia was observed. No rebound tachycardia was noted after the hemodialysis termination. However, due to severe septic shock, hypotension persisted, and vasoactive medications were adjusted. However, the measured levels of plasma salbutamol do not support the view that hemodialysis was the cause of the described improvement. The total amount of the drug cleared was exceedingly small, only 2.8% of the total dose. Data from the literature support our findings, even in the case of the life-threatening intoxication described. Conclusion The results confirm a large volume of distribution for salbutamol. The measured half-life time during hemodialysis (3.1 hours) is comparable to observed half-life times in therapeutic settings. The observed clinical benefit associated with dialysis appears to be fortuitous. This case report highlights the potential bias towards positive clinical outcomes and unproven therapies.

Development of Nontoxic Peptides for Lipopolysaccharide Neutralization and Sepsis Treatment.

Host defense peptides (HDPs), also named antimicrobial peptides (AMPs), are increasingly being recognized for serving multiple functions in protecting the host from infection and disease. Previous studies have shown that various HDPs can also neutralize lipopolysaccharide (LPS, endotoxin), as well as lipoteichoic acid (LTA), inducing macrophage activation. However, antimicrobial activity is usually accompanied by systemic toxicity which makes it difficult to use HDPs as antiendotoxin agents. Here we report that key parameters can uncouple these two functions yielding nontoxic peptides with potent LPS and LTA neutralization activities in vitro and in animal models. The data reveal that peptide length, the number, and the placement of positive charges are important parameters involved in LPS neutralization. Crucially, the peptide exhibited a separation between its membrane-disrupting and antimicrobial properties, effectively decoupling them from its ability to neutralize LPS. This essential distinction prevented systemic toxicity and led to the peptide's complete rescue of mice suffering from severe septic shock in two distinct models. Strong binding to LPS, changes in structure, and oligomerization state upon LPS binding were important factors that determined the activity of the peptides. In the face of the increasing threat of septic shock worldwide, it is crucial to grasp how we can neutralize harmful substances like LPS. This knowledge is vital for creating nontoxic treatments for sepsis.

Early acute kidney injury in sepsis and septic shock

ABSTRACT Background: Acute kidney injury is one of the severe conditions in hospitalized patients. Acute kidney injury can develop early from admission, usually within the first 24 hours of ICU admission. In Vietnam, there have been limited studies monitoring the progression of acute kidney injury in the early stages. This study aims to investigate the incidence, severity, clinical, laboratory characteristics, and progression of acute kidney injury in patients with sepsis and septic shock within the first 48 hours. Methods: This study is a cross-sectional descriptive analysis of 101 patients who are 15 or older and have been diagnosed with severe infection and septic shock. These patients were treated in the Intensive Care Unit of Hue Central Hospital. The patient had treatment in accordance with a standardized protocol while being closely observed. Samples were collected for diagnostic testing, and the patient’s urine output and blood creatinine levels were diligently checked. Results: The prevalence of acute renal injury (AKI) was 60.40%, with stage 1 accounting for 50.82% of cases, stage 2 accounting for 22.95%, and stage 3 accounting for 26.23%. The cohort of individuals diagnosed with AKI exhibited an advanced age, with a mean age of 60.72 ± 17.41 years, and predominantly consisted of male subjects. Patients diagnosed with acute kidney injury showed a statistically significant decrease in urine output and an increased incidence of shock (p < 0.05). Additionally, these patients demonstrated lower levels of Hct, blood pH, and bicarbonate while exhibiting higher levels of blood urea, blood creatinine, AST, ALT, total bilirubin, PCT, and blood lactate (p < 0.05) compared to individuals without AKI. Patients with AKI had significantly elevated SOFA and APACHE II scores compared to individuals without AKI, as indicated by statistical analysis (p < 0.05). Upon admission, a significant proportion of patients, precisely 81.97%, experienced the development of AKI. Furthermore, a observation was made about the prompt recovery of these patients within the initial 24 and 48 hours following admission. Conclusion: The prevalence of AKI was accounted for 60.40%. Among the cases of AKI, stage 1 accounted for 50.82%, while stage 2 and stage 3 accounted for 22.95% and 26.23%, respectively. There were observed variations in urine output and rates of shock among individuals diagnosed with AKI. Additionally, SOFA and APACHE II scores were elevated. The percentage of AKI was 81.97% of patients upon their initial hospital admission, with a significant proportion seeing early recovery within the first 24 to 48 hours.

Lactate dynamics in paediatric patients with severe sepsis: insights from a prospective cohort study

BackgroundSepsis is an infection-related systemic inflammatory response that often leads to elevated lactate levels. Monitoring lactate levels during severe sepsis is vital for influencing clinical outcomes. The aim of this study was to assess the association between plasma lactate levels and mortality in children with severe sepsis or septic shock.MethodsThe current prospective study was conducted in the PICU of University Children’s Hospital. The International Paediatric Sepsis Consensus Conference criteria for Definitions of Sepsis and Organ Failure in 2005 were used to diagnose patients with sepsis. We measured plasma lactate levels upon admission (Lac H0) and 6 h later (Lac H6). The static indices included the absolute lactate values (Lac H0 and Lac H6), while the dynamic indices included the delta-lactate level (ΔLac) and the 6-hour lactate clearance. The 6-hour lactate clearance was calculated using the following formula: [(Lac H0–Lac H6)100/Lac H0]. ΔLac was calculated as the difference between the Lac H0 and Lac H6 levels. Patient survival or death after a PICU stay was the primary outcome.ResultsA total of 46 patients were included in this study: 25 had septic shock, and 21 had severe sepsis. The mortality rate was 54.3%. The Lac H0 did not significantly differ between survivors and nonsurvivors. In contrast, the survivors had significantly lower Lac H6 levels, higher ΔLac levels, and higher 6-hour lactate clearance rates than nonsurvivors. Lactate clearance rates below 10%, 20%, and 30% were significantly associated with mortality. The best cut-off values for the lactate clearance rate and Lac H6 for the prediction of mortality in the PICU were < 10% and ≥ 4 mmol/L, respectively. Patients with higher Lac H6 levels and lower lactate clearance rates had significantly higher PICU mortality based on Kaplan–Meier survival curve analysis.ConclusionsThis study highlights the significance of lactate level trends over time for the prediction of mortality in the PICU in patients with severe sepsis or septic shock. Elevated lactate levels and decreased lactate clearance six hours after hospitalisation are associated with a higher mortality rate.

Multimodal Quality Initiatives in Sepsis Care: Assessing Impact on Core Measures and Outcomes.

Providing timely and effective care for patients with sepsis is challenging due to delays in recognition and intervention. The Surviving Sepsis Campaign has developed bundles that have been shown to reduce sepsis mortality. However, hospitals have not consistently adhered to these bundles, resulting in suboptimal outcomes. To address this, a multimodal quality improvement sepsis program was implemented from 2017 to 2022 in a large urban tertiary hospital. The aim of this program was to enhance the Severe Sepsis and Septic Shock Management Bundle compliance and reduce sepsis mortality. At baseline, the Severe Sepsis and Septic Shock Management Bundle compliance rates were low, at 25%, with a sepsis observed/expected mortality ratio of 1.14. Our interventions included the formation of a multidisciplinary committee, the appointment of sepsis champions, the implementation of sepsis alerts and order sets, the formation of a Code Sepsis team, real-time audits, and peer-to-peer education. By 2022, compliance rose to 62%, and the observed/expected mortality ratio decreased to 0.73. Our approach led to improved outcomes and hospital rankings. These findings underscore the efficacy of a comprehensive sepsis care initiative, emphasizing the importance of interdisciplinary collaboration. A multimodal hospital-wide sepsis performance program is feasible and can contribute to improved outcomes. However, further research is necessary to determine the specific impact of individual strategies on sepsis outcomes.

Sepsis best practices: Definitions, guidelines, and updates.

Sepsis remains a complex and costly disease with high morbidity and mortality. This article discusses Sepsis-2 and Sepsis-3 definitions, highlighting the 2021 Surviving Sepsis International guidelines as well as the regulatory requirements and reimbursement for the Severe Sepsis and Septic Shock Management Bundle (SEP-1) measure.

PERCUTANEOUS LEFT STELLATE GANGLION BLOCK TO INCREASE VENTRICULAR FIBRILLATION THRESHOLD AND DEFIBRILLATION SUCCESS RATE IN ACUTE FULMINANT MYOCARDITIS WITH ELECTRICAL STORM

Abstract Introduction Acute fulminant myocarditis represents a predisposing substrate for life–threatening ventricular arrhythmias (VAs). Percutaneous left stellate ganglion block (PLSGB) usage has been reported for the prevention of recurrent VAs, but clinical data on its acute effect on ongoing ventricular fibrillation (VF) are missing. Case A 57–years–old man suffering gastroenteritis and fever in the past week presented in the ED with typical chest pain. ECG depicted infero–lateral ST–segment elevation, cardiac ultrasound showed a mildly reduced LVEF and coronary angiography ruled out coronary lesions. In the following hours the patient developed frequent premature ventricular complexes with R on T phenomenon triggering short coupled torsade de pointes with rapid degeneration into VF. VAs episodes, initially responsive to single DC shock, kept recurring despite intravenous (iv) amiodarone, iv lidocaine and iv correction of potassium and magnesium. The patient was therefore treated with deep sedation, intubation and ECMO VA placement; still, he reached a status of persistently ongoing VF, refractory even to DC shocks (n=20). Therefore, ultrasound–guided PLSGB using a local bolus of lidocaine 150 mg + ropivacaine 50 mg was performed. After 5 minutes, a single DC shock was delivered, effective in achieving a stable sinus rhythm at 35 bpm with no more recurrences. Despite electrical stabilization, the patient developed a severe cardiogenic shock due to bradycardia and severe biventricular disfunction, treated with vasopressin and dobutamine. In the next 48 hours we observed a significant improvement, resumption of biventricular contractility and absence of VAs recurrences, so the patient was slowly weaned off ECMO and vasopressors. Immunological tests showed Enterovirus IgM positivity, while endomyocardial biopsy was negative for inflammatory infiltrates in the analyzed sections. Cardiac MRI (performed 10 days after onset) showed edema and non–ischemic LGE in the antero–lateral and infero–lateral basal subepicardial regions of the left ventricle, LVEF was 55%. After 15 days from admission, despite ongoing amiodarone and bisoprolol, the patient developed a run of monomorphic VA of 30 beats at 170 bpm, therefore he underwent sICD implantation. Conclusion PLSGB played a key role for the acute management of refractory VF unresponsive to DC shocks, allowing for acute stabilization. More clinical data are needed on acute neuromodulation for electrical storm.

Impact of timing of antimicrobial therapy on outcome and mortality in severe sepsis and septic shock

Even though new antimicrobial treatments have been available for over 60 years, the fatality rate from septic shock has not decreased. Evolutionary pressure on microbial pathogens has, as expected, led to selection towards resistant species as a consequence of the creation of ever more broad-spectrum and strong antimicrobials. The ineffectiveness of antibiotic treatment of septic shock un the decades that followed may have been a result of this phenomena. The treatment of septic shock has traditionally focused on resuscitative measures. The management of these serious illnesses has not prioritised the prompt provision of effective antibiotic treatment.

Intravenous angiotensin II as an add-on to standard of care vasopressors in patients with refractory shock on mechanical circulatory support: a single centre retrospective case series

Abstract Funding Acknowledgements None. Background Refractory shock is life-threatening condition characterized by hypotension with mean arterial pressure (MAP) less than 65 mmHg and end-organ dysfunction, despite volume resuscitation and high doses of vasopressors. Mortality rates in refractory shock exceeds 90%. Angiotensin II (Ang II) is a non-catecholamine vasopressor that targets the renin-angiotensin-aldosterone system by agonism of the angiotensin type 1 receptors. Ang II has been studied in settings of vasodilatory shock, however there is paucity of data regarding the usage of Ang II in patients with preexisting heart failure or in patients requiring mechanical circulatory support (MCS), either short term such as venoarterial extracorporeal membrane oxygenation (VA-ECMO) or long term such as left ventricular assist device (LVAD) (1,2). Purpose This report is aimed to analyse baseline characteristics of patients who have received Ang II from the moment it became available in our institution (January 2023). Methods Five patients were included in this retrospective analyses. Demographic, clinical and laboratory parameters as well as hourly changes of vasopressors doses, MAP, lactates, and diuresis were collected and analysed. Results Median age of 5 included patients, 4 of whom were male, was 53 years old (range 18-57). The most common comorbidities were chronic kidney disease (n=3), diabetes mellitus (n=3) and arterial hypertension (n=3), treated with valsartan as chronic therapy. All patients presented with severe shock. 4 patients were on VA-ECMO support, 1 had additionally implanted Impella for left ventricular unloading and 2 had implanted LVAD. All patients had severely reduced left ventricular ejection fraction (median 15%, range 10-25%). In 4 cases vasopressors were initiated due to sepsis and in 1 case during cardiopulmonary resuscitation. Median values prior to administration of Ang II were as following: MAP 51 mmHg (range 41-56 mmHg), lactates 6.7 mmol/L (range 2.4-10.7 mmol/L) and Sequential Organ Failure Assessment (SOFA) score 9 (range 5-11). Four hours following administration of Ang II median MAP was 61 mmHg (range 54-77 mmHg). Patient who ultimately survived had better response to Ang II, with median rise of MAP of 22 mmHg (range 12-22 mmHg). In contrast, patients who ultimately died didn’t respond to Ang II, with rise of MAP of only 2.5 mmHg. Median duration of Ang II administration was 52 h (range 20-96 h). 60% of patients are alive up to the present day. Complete patient data are shown in Table 1. Hourly changes of vasopressor doses and MAP are shown in Figure 1. Conclusion Ang II is an effective vasopressor with rapid effect. This case series suggests that it may be considered as salvage treatment option in patients on MCS with refractory shock. Patients who responded to Ang II had better survival, similar to previous findings. Therefore, Ang II should be considered in earlier phases of shock when maximum doses of vasopressors have not yet been reached.

Serial invasive hemodynamics and clinical characteristics of patients with shock with and without invasive mechanical ventilation

Abstract Funding Acknowledgements None. Background Invasive mechanical ventilation (IMV) is commonly used in the Cardiac Intensive Care Unit (CICU) in patients with cardiogenic shock (CS). IMV causes hemodynamic changes that may impact outcomes based upon a patient’s profile. Our aim is to characterize the clinical profile and detailed serial hemodynamic parameters in the first 24-hours according to the use of IMV in patients with shock admitted to the CICU. Methods Retrospective analysis of consecutive patients with shock admitted to the CICU at Bellevue Hospital, undergoing pulmonary artery catheter (PAC) placement within the first 24 hours of admission, from February 2022 to June 2023. Clinical characteristics, as well as specific hemodynamic parameters collected and curated at times 0, 6, 12, 18 and 24 hours were from PAC placement compared between patients with and without IMV. Results A total of 101 patients were included (95% with cardiogenic shock), 59 receiving IMV (age 64 ± 15, 24% women) and 42 non-intubated (61 ± 13, 33% women). Non-intubated patients had higher prevalence of hypertension, prior coronary artery disease and heart failure with reduced ejection fraction (HFrEF), while acute coronary syndromes (44%) and cardiac arrest (12%) were more common causes of admission in patients undergoing IMV. Mixed shock predominated in IMV patients (51 vs 17%, p &amp;lt;0.001), whereas cardiogenic shock (CS) was more common in non-intubated patients (83 vs 41%, p &amp;lt;0.01). Patients with acute myocardial infarction CS (AMI-CS) were more likely to undergo IMV, while patients with heart failure CS (HF-CS) were more likely to be non-intubated. Patients undergoing IMV were more likely to have mechanical circulatory support (MCS) and ventricular dilatation compared to non-intubated patients (LVEDD 5.7 cm vs 4.9 cm, p 0.002). Patients undergoing IMV had a higher incidence of severe shock compared to the non-intubated group (31% vs 19% SCAI Shock D), higher lactate levels and greater use of vasoactive drugs (figure 1A). Patients undergoing IMV had significant improvements in cardiac power output (CPO), diastolic blood pressure and systemic vascular resistance (SVR) (figure 1B). Shock severity by SCAI SHOCK classification had a more notable improvement at 24 hours in patients with IMV compared to non-intubated patients (figure 1C), with a non-statistically significant improvement in lactate clearance in the first 24 hours (Figure 1D). Conclusions IMV in patients with CS is more commonly seen in patients with AMI-CS and among those with higher baseline shock severity and greater use of vasoactive medications. IMV is associated with significant improvements in shock severity, CPO and SVR at 24 hours when compared to patients with shock who are not intubated, which could be related to higher use of vasopressors. Further investigations are warranted to understand the impact of IMV on outcomes of patients with CS and how they might vary according to hemodynamic profile.

Comparison of shelf-stable and conventional resuscitation products in a canine model of hemorrhagic shock.

Treatment of severe hemorrhagic shock typically involves hemostatic resuscitation with blood products. However, logistical constraints often hamper the wide distribution of commonly used blood products like whole blood. Shelf-stable blood products and blood substitutes are poised to be able to effectively resuscitate individuals in hemorrhagic shock when more conventional blood products are not readily available. Purpose-bred adult dogs (n = 6) were anesthetized, instrumented, and subjected to hemorrhagic shock (mean arterial pressure <50 mm Hg or 40% blood volume loss). Then each dog was resuscitated with one of five resuscitation products: (1) lactated ringers solution and hetastarch (LRS/Heta), (2) canine chilled whole blood (CWB), (3) fresh frozen plasma (FFP) and packed red blood cells (pRBC), (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC), or (5) HBOC/FDP and canine lyophilized platelets (LyoPLT). Each dog was allowed to recover after the hemorrhage resuscitation event and was then subjected to another hemorrhage event and resuscitated with a different product until each dog was resuscitated with each product. At the time when animals were determined to be out of shock as defined by a shock index <1, mean arterial pressure (mmHg) values (mean ± standard error) were higher for FFP/pRBC (n = 5, 83.7 ± 4.5) and FDP/HBOC+LyoPLT (n = 4, 87.8 ± 2.1) as compared with WB (n = 4, 66.0 ± 13.1). A transient increase in creatinine was seen in dogs resuscitated with HBOC and FDP. Albumin and base excess increased in dogs resuscitated with HBOC and FDP products compared with LRS/heta and CWB ( p < 0.01). Combinations of shelf-stable blood products compared favorably to canine CWB for resolution of shock. Further research is needed to ascertain the reliability and efficacy of these shelf-stable combinations of products in other models of hemorrhage that include a component of tissue damage as well as naturally occurring trauma.

Pigment epithelium‑derived factor inhibits proliferation, invasion and angiogenesis, and induces ferroptosis of extravillous trophoblasts by targeting Wnt‑β‑catenin/VEGF signaling in placenta accreta spectrum.

Placenta accreta spectrum (PAS) is one of the most dangerous complications in obstetrics, which can lead to severe postpartum bleeding and shock, and even necessitate uterine removal. The abnormal migration and invasion of extravillous trophoblast cells (EVTs) and enhanced neovascularization occurring in an uncontrolled manner in time and space are closely related to the abnormal expression of pro‑angiogenic and anti‑angiogenic factors. The pigment epithelium‑derived factor (PEDF) is a multifunctional regulatory factor that participates in several important biological processes and is recognized as the most efficient inhibitor of angiogenesis. The present study aimed to explore the effects of PEDF on EVT phenotypes and the underlying mechanisms in PAS. HTR‑8/SVneo cells were transfected to overexpress or knock down PEDF. Cell proliferation and invasion were assessed using Cell Counting Kit‑8, 5‑ethynyl‑2'‑deoxyuridine and Transwell assays. In vitro angiogenesis was analyzed using tube formation assays. The degree of ferroptosis was assessed by evaluating the levels of lipid reactive oxygen species, total iron, Fe2+, malondialdehyde and reduced glutathione using commercial kits. The expression levels of biomarkers of ferroptosis, angiogenesis, cell proliferation and Wnt signaling were examined by western blotting. PEDF overexpression decreased the proliferation, invasion and angiogenesis, and induced ferroptosis of EVTs. Activation of Wnt signaling with BML‑284 and overexpression of vascular endothelial growth factor (VEGF) reversed the PEDF overexpression‑induced suppression of cell proliferation, invasion and tube formation. PEDF overexpression‑induced ferroptosis was also decreased by Wnt agonist treatment and VEGF overexpression. It was predicted that PEDF suppressed the proliferation, invasion and angiogenesis, and increased ferroptosis in EVTs by decreasing Wnt‑β‑catenin/VEGF signaling. The findings of the present study suggested a novel regulatory mechanism of the phenotypes of EVTs and PAS.

Activation of trace amine-associated receptor 1 ameliorates PTSD-like symptoms

Trace amine-associated receptor 1 (TAAR1) negatively modulates monoaminergic transmission in the mammalian brain and participates in many psychiatric disorders. Preclinical evidence indicate that selective TAAR1 agonists have anxiolytic effects and anti-stress properties. Post-traumatic stress disorder (PTSD) is an anxiety disorder triggered by experiencing or witnessing traumatic stressors. However, it remains unknown whether TAAR1 is involved in PTSD. Here, we investigated the role of TAAR1 in two PTSD animal models, including single prolonged stress (SPS)-induced impairment of fear extinction and stress-enhanced fear learning (SEFL). SPS decreased TAAR1 mRNA levels in the prefrontal cortex and ventral tegmental area. Acute treatment of the TAAR1 partial agonist RO5263397 attenuated SPS-induced anxiety-like behavior evaluated by the elevated-plus maze test. Compared to non-stressed animals, rats that experienced SPS showed higher freezing levels in the extinction retention test, indicating an impairment of fear extinction retention after SPS exposure. Acute and chronic treatment of RO5263397 ameliorated SPS-induced impairment of fear extinction retention. In the SEFL model, compared to the No-shock group, rats that experienced severe foot shock before fear conditioning showed higher freezing levels during the tests, indicating enhanced fear learning after stress exposure. Chronic treatment of RO5263397 partially attenuated the SEFL. Moreover, chronic treatment with the selective TAAR1 full agonist RO5166017 completely prevented the SEFL. Taken together, these data showed that pharmacological activation of TAAR1 could ameliorate PTSD-like symptoms. The present study thus provides the first evidence that TAAR1 might participate in the development of PTSD, and TAAR1 agonists could be potential pharmacological treatments for this disorder.

Immediate inflammatory response to mechanical circulatory support in a porcine model of severe cardiogenic shock

BackgroundIn selected cases of cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is combined with trans valvular micro axial flow pumps (ECMELLA). Observational studies indicate that ECMELLA may reduce mortality but exposing the patient to two advanced mechanical support devices may affect the early inflammatory response. We aimed to explore inflammatory biomarkers in a porcine cardiogenic shock model managed with V-A ECMO or ECMELLA.MethodsFourteen landrace pigs had acute myocardial infarction-induced cardiogenic shock with minimal arterial pulsatility by microsphere embolization and were afterwards managed 1:1 with either V-A ECMO or ECMELLA for 4 h. Serial blood samples were drawn hourly and analyzed for serum concentrations of interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha, and serum amyloid A (SAA).ResultsAn increase in IL-6, IL-8, and SAA levels was observed during the experiment for both groups. At 2–4 h of support, IL-6 levels were higher in ECMELLA compared to V-A ECMO animals (difference: 1416 pg/ml, 1278 pg/ml, and 1030 pg/ml). SAA levels were higher in ECMELLA animals after 3 and 4 h of support (difference: 401 ng/ml and 524 ng/ml) and a significant treatment-by-time effect of ECMELLA on SAA was identified (p = 0.04). No statistical significant between-group differences were observed in carotid artery blood flow, urine output, and lactate levels.ConclusionsLeft ventricular unloading with Impella during V-A ECMO resulted in a more extensive inflammatory reaction despite similar end-organ perfusion.

Excessive pickle consumption: beware of adrenal crisis

Adrenal insufficiency (AI) is one of the most life-threatening disorders resulting from adrenal cortex dysfunction. Symptoms and signs of AI are often nonspecific, and the diagnosis can be missed and lead to the development of AI with severe hypotension and hypovolemic shock.We report the case of a 13-year-old child admitted for cardiac arrest following severe hypovolemic shock. The patient initially presented with isolated mild abdominal pain and vomiting together with unexplained hyponatremia. He was discharged after an initial short hospitalization with rehydration but with persistent hyponatremia. After discharge, he had persistent refractory vomiting, finally leading to severe dehydration and extreme asthenia. He was admitted to pediatric intensive care after prolonged hypovolemic cardiac arrest with severe anoxic encephalopathy leading to brain death. After re-interviewing, the child's parents reported that he had experienced polydipsia, a pronounced taste for salt with excessive consumption of pickles lasting for months, and a darkened skin since their last vacation 6 months earlier. A diagnosis of autoimmune Addison's disease was made.Primary AI is a rare life-threatening disease that can lead to hypovolemic shock. The clinical symptoms and laboratory findings are nonspecific, and the diagnosis should be suspected in the presence of unexplained collapse, hypotension, vomiting, or diarrhea, especially in the case of hyponatremia.

Continuation of chronic antiplatelet therapy is not associated with increased need for transfusions: a cohort study in critically ill septic patients.

The decision to maintain or halt antiplatelet medication in septic patients admitted to intensive care units presents a clinical dilemma. This is due to the necessity to balance the benefits of preventing thromboembolic incidents and leveraging anti-inflammatory properties against the increased risk of bleeding. This study involves a secondary analysis of data from a prospective cohort study focusing on patients diagnosed with severe sepsis or septic shock. We evaluated the outcomes of 203 patients, examining mortality rates and the requirement for transfusion. The cohort was divided into two groups: those whose antiplatelet therapy was sustained (n = 114) and those in whom it was discontinued (n = 89). To account for potential biases such as indication for antiplatelet therapy, propensity score matching was employed. Therapy continuation did not significantly alter transfusion requirements (discontinued vs. continued in matched samples: red blood cell concentrates 51.7% vs. 68.3%, p = 0.09; platelet concentrates 21.7% vs. 18.3%, p = 0.82; fresh frozen plasma concentrates 38.3% vs. 33.3%, p = 0.7). 90-day survival was higher within the continued group (30.0% vs. 70.0%; p < 0.001) and the Log-rank test (7-day survivors; p = 0.001) as well as Cox regression (both matched samples) suggested an association between continuation of antiplatelet therapy < 7 days and survival (HR: 0.24, 95%-CI 0.10 to 0.63, p = 0.004). Sepsis severity expressed by the SOFA score did not differ significantly in matched and unmatched patients (both p > 0.05). The findings suggest that continuing antiplatelet therapy in septic patients admitted to intensive care units could be associated with a significant survival benefit without substantially increasing the need for transfusion. These results highlight the importance of a nuanced approach to managing antiplatelet medication in the context of severe sepsis and septic shock.

Sulfuric Acid Ingestion: May the Severity of the Metabolic Acidosis be Considered as a Predictive Sign of Late Damage to the Gastrointestinal Tract?

Caustic substances ingestion results in a complex syndrome. The patient characteristics and severity of injury are important prognostic predictors. The monitoring of clinical changes and the multidisciplinary approach are necessary to prevent death in the early stages of the poisoning. The case report describes the suicide of a woman by ingestion of a large amount of 15% sulfuric acid for suicidal purposes (15-20 ml). The initial conditions were stable, and no changes were found on a CT scan. However, the main sign was a severe metabolic acidosis. After 7 hours, haematemesis and oedema of the larynx appeared, and oro-tracheal intubation and ICU admission were necessary. Consequent progressive haemodynamic deterioration with persistent severe metabolic acidosis, increasing lactates and septic shock appeared. A new CT scan with contrast was performed 22 hours later detecting diffuse perforations and liquid in pleurae and abdomen. A pleural sample showed necrotic liquid. The death was 24 hours after ingestion and no surgical treatment was performed because of the diffuse lesions to the thoracoabdominal districts. Early detection of gastroenteric lesions and the monitoring of clinical changes are mandatory to avoid the death of the patient. Gastroenteric perforations require an immediate radiological evaluation and surgical treatment. The clinical case report states the severity of prognosis was related to high doses of sulfuric acid ingestion. The immediate metabolic acidosis is related to quick subsequent severe systemic pathological lesions of the gastrointestinal tract. The severity of absorption metabolic acidosis, consequently, may be an early and prognostic sign of the late chest and abdominal lesions. Severity of metabolic acidosis after sulfuric acid ingestion may anticipate late damage to the gastrointestinal tract.

Comparative Study of Fetomaternal Outcome in Abruptio Placenta and Placenta Previa

Background: Abruptio placenta and placenta previa are obstetric complications associated with significant risks for both the fetus and the mother, potentially leading to severe hemorrhage, preterm birth, and maternal shock. Early detection and prompt medical intervention are crucial for optimizing outcomes and reducing maternal and fetal morbidity and mortality.&#x0D; Objective: The study aims to analyze the maternal and perinatal outcomes of APH cases due to placenta previa and abruptio placenta.&#x0D; Methods: This prospective study conducted at Ad Din Akij Medical College, Boyra, Khulna July 1, 2021, to June 30, 2023, included 150 APH cases, with 109 meeting inclusion criteria for comparison between placenta previa and abruptio placenta. Data collection encompassed maternal demographics, obstetric history, severity of hemorrhage, and neonatal outcomes. Diagnosis was based on clinical evaluation and ultrasound. Statistical analysis was performed using MS Excel.&#x0D; Results: In our Study, the distribution of causes of placental issues reveals that Placenta Previa accounts for the majority, comprising 71.55% of cases, while Abruptio Placentae represents 28.44% of instances. Placenta Previa predominantly affects individuals aged 26-30 years and over 35 years, with the highest occurrence among those with 2 pregnancies. Conversely, Abruptio Placentae shows a varied distribution across age groups, with the highest incidence among those aged 31-35 years and with gravidity of 1 pregnancy. Gestationally, the majority of Abruptio Placentae cases present between 31-33 weeks, while Placenta Previa cases peak at 34-36.6 weeks. Preterm births are prevalent in both conditions, with Placenta Previa leading in preterm deliveries. Placenta Previa is associated with a history of abortion and dilation and curettage (D&amp;C), while hypertension is a significant risk factor for Abruptio Placentae. Maternal complications include anemia, postpartum hemorrhage (PPH), and shock, with Placenta Previa being associated with anemia and PPH, while Abruptio Placentae correlated with shock.&#x0D; Conclusion: Placenta previa emerged as the primary cause of APH, affecting multiparous women, while abruptio placenta correlated with hypertension and primigravida. Both conditions posed significant risks of maternal and perinatal morbidity and mortality, highlighting the importance of prompt diagnosis and intervention.