Severe Multiorgan Dysfunction Research Articles

Prolonged ECMO Support in a Pediatric Patient with Complex Cardiac Conditions During Wartime in Kyiv, Ukraine

Background: Managing complex medical interventions in conflict-affected Kyiv, Ukraine, poses significant challenges, particularly for critically ill pediatric patients. This case report examines the extended use of extracorporeal membrane oxygenation (ECMO) in a 12-year-old girl with severe congenital heart disease, including critical aortic stenosis and myocarditis. With no transplant system and limited resources, alternative solutions were necessary to maintain ECMO support and mitigate complications over a prolonged period. Methods: The patient was on ECMO support for 259 days, utilizing both VV-ECMO and VA-ECMO configurations. Wartime supply issues necessitated the use of polypropylene fiber oxygenators (Quadrox-i and Terumo Fx15), despite their unsuitability for long-term use. Eleven oxygenators were used, with ten replacements due to thrombosis and malfunctions. The oxygenators included EUROSETS Alone, Maquet PLS, Paragon, Terumo Fx15, and Quadrox-i. Care involved frequent ECMO parameter adjustments, infection control, and daily rehabilitation. Cardiac function recovery was consistently negative. Results: Performance of the oxygenators declined over time, necessitating frequent replacements due to clotting, reduced oxygen exchange, and lower CO2 removal efficiency. Usage durations varied: EUROSETS (10, 32, 88, and 26 days), Paragon (78 days), Maquet PLS (14 days), Terumo Fx15 (1-5 days), and Quadrox-i (1 day). EUROSETS nr 3 lasted 88 days, and the Paragon provided 78 days of stable support. The Maquet PLS lasted 14 days, while the Terumo Fx15 and Quadrox-i required replacements within 1 to 5 days. ECMO was discontinued due to irreversible heart failure, with the patient passing away from severe multi-organ dysfunction and complications. Conclusions: This case highlights the extraordinary challenges of prolonged ECMO use in a pediatric patient within a war zone, emphasizing the resilience and adaptability required from healthcare teams in resource-limited settings. The logistical constraints and the necessity to use suboptimal oxygenators underscore the need for international support and mobilization to sustain advanced care in conflict-affected regions.

The correlation between severe asymptomatic carotid artery stenosis and severe multi-organ dysfunction after off-pump coronary artery bypass grafting.

The current research aimed to demonstrate the independent association between preoperative severe asymptomatic carotid artery stenosis (ACAS) and severe multi-organ dysfunction after off-pump coronary artery bypass grafting (OPCAB), which may further indicate the relationship between severe ACAS and adverse 30-day postoperative outcomes of patients undergoing OPCAB. This was a single-center, retrospective observational study including patients without a history of stroke or Transient Ischemic Attacks (TIA) (asymptomatic), who underwent for an isolated OPCAB in the center for operative treatment of coronary artery disease of Beijing Anzhen Hospital from January 2020 to December 2021. All enrolled patients underwent carotid artery ultrasound prior to OPCAB. The information was extracted independently by two authors of the study from the medical records. Both univariate and multivariate analyses were conducted. A total of 562 patients met the inclusion criteria for the current study. 63 (11.2%) suffered from severe ACAS. The Sequential Organ Failure Assessment (SOFA) maximum in the severe ACAS group was significantly higher than that in the non-severe ACAS group (9.76 ± 3.03 vs. 7.75 ± 2.96, p < 0.0001), and a higher proportion of patients in the severe ACAS group exhibited severe multi-organ dysfunction (44.4% vs. 14.0%, p < 0.0001). In addition, severe ACAS was related to an increased rate of 30-day postoperative major adverse cardiovascular and cerebral events (MACCEs), including a 30-day postoperative stroke. Severe ACAS was associated with an elevated risk of delirium, and acute kidney injury (AKI). The results of the multivariate analysis demonstrated that severe ACAS may be independently associated with severe multi-organ dysfunction (OR, 7.37, 95% CI 4.80-14.30, p < 0.0001) after OPCAB. Also, severe ACAS may be independently associated with 30-day postoperative stroke (OR, 2.83, 95% CI 1.03-7.75, p = 0,043). Severe ACAS was independently associated with severe multi-organ dysfunction after OPCAB, which may be associated further with an increased rate of 30-day postoperative mortality and complications. This study highlights: (1) the importance of personalized assessment for potential advantages and disadvantages in prognosis of severe ACAS patients undergoing OPCAB with carotid endarterectomy; (2) the role of multi-organ parameters, especially cardio-cerebral factors, should be emphasized during the process of severe ACAS management.

Current status of research on the diagnosis and treatment of acute ethylene glycol poisoning

Acute ethylene glycol poisoning often leads to acute kidney injury, and delays in diagnosis and treatment can lead to severe multi-organ dysfunction and even death. At present, there is a lack of specific laboratory tests that can be used for rapid clinical diagnosis, and diagnosis and evaluation only rely on medical history, clinical symptoms, and non-specific laboratory test results. Key treatments include alcohol dehydrogenase inhibitors (fomcpizole or ethanol) and hemodialysis, which is not approved in China. A clear understanding of the mechanism of toxicity, pathophysiology, clinical manifestations, efficacy and limitations of laboratory tests, and treatment options after ethylene glycol poisoning can help accelerate the early diagnosis, treatment, and prognosis of patients after ethylene glycol poisoning. This article reviews this article in order to provide a reference for clinicians.

Derivation and validation of generalized sepsis-induced acute respiratory failure phenotypes among critically ill patients: a retrospective study

BackgroundSeptic patients who develop acute respiratory failure (ARF) requiring mechanical ventilation represent a heterogenous subgroup of critically ill patients with widely variable clinical characteristics. Identifying distinct phenotypes of these patients may reveal insights about the broader heterogeneity in the clinical course of sepsis, considering multi-organ dynamics. We aimed to derive novel phenotypes of sepsis-induced ARF using observational clinical data and investigate the generalizability of the derived phenotypes.MethodsWe performed a multi-center retrospective study of ICU patients with sepsis who required mechanical ventilation for ≥ 24 h. Data from two different high-volume academic hospital centers were used, where all phenotypes were derived in MICU of Hospital-I (N = 3225). The derived phenotypes were validated in MICU of Hospital-II (N = 848), SICU of Hospital-I (N = 1112), and SICU of Hospital-II (N = 465). Clinical data from 24 h preceding intubation was used to derive distinct phenotypes using an explainable machine learning-based clustering model interpreted by clinical experts.ResultsFour distinct ARF phenotypes were identified: A (severe multi-organ dysfunction (MOD) with a high likelihood of kidney injury and heart failure), B (severe hypoxemic respiratory failure [median P/F = 123]), C (mild hypoxia [median P/F = 240]), and D (severe MOD with a high likelihood of hepatic injury, coagulopathy, and lactic acidosis). Patients in each phenotype showed differences in clinical course and mortality rates despite similarities in demographics and admission co-morbidities. The phenotypes were reproduced in external validation utilizing the MICU of Hospital-II and SICUs from Hospital-I and -II. Kaplan–Meier analysis showed significant difference in 28-day mortality across the phenotypes (p < 0.01) and consistent across MICU and SICU of both Hospital-I and -II. The phenotypes demonstrated differences in treatment effects associated with high positive end-expiratory pressure (PEEP) strategy.ConclusionThe phenotypes demonstrated unique patterns of organ injury and differences in clinical outcomes, which may help inform future research and clinical trial design for tailored management strategies.

Immune Profile in COVID-19: Unveiling TR3-56 Cells in SARS-CoV-2 Infection.

The emergence of COronaVIrus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presented a global health challenge since its identification in December 2019. With clinical manifestations ranging from mild respiratory symptoms to severe multi-organ dysfunction, COVID-19 continues to affect populations worldwide. The complex interactions between SARS-CoV-2 variants and the human immune system are crucial for developing effective therapies, vaccines, and preventive measures. Understanding these immune responses highlights the intricate nature of COVID-19 pathogenesis. This retrospective study analyzed, by flow cytometry approach, a cohort of patients infected with SARS-CoV-2 during the initial pandemic waves from 2020 to 2021. It focused on untreated individuals at the time of hospital admission and examined the presence of TR3-56 cells in their immune profiles during the anti-viral immune response. Our findings provide additional insights into the complex immunological dynamics of SARS-CoV-2 infection and highlight the potential role of TR3-56 cells as crucial components of the immune response. We suggest that TR3-56 cells could serve as valuable biomarkers for identifying more severe cases of COVID-19, aiding in the assessment and management of the disease.

Emapalumab as a therapeutic intervention for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: A case series.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is characterized by a severe cytokine storm, heightened inflammatory response, and immune-mediated damage to tissues and organs. Standard treatment protocols for hemophagocytic lymphohistiocytosis often fall short in effectively controlling EBV-HLH, leading to a need for novel therapeutic options. Emapalumab, a monoclonal antibody targeting interferon-gamma, has shown promise due to its targeted cytokine modulation capabilities and favorable safety profile. This study aimed to evaluate the efficacy and safety of emapalumab in pediatric patients with EBV-HLH. The case series involved 4 pediatric patients diagnosed with EBV-HLH who did not achieve disease control despite receiving comprehensive treatment. All 4 pediatric patients were diagnosed with EBV-HLH. Emapalumab was introduced as an adjunctive therapeutic intervention alongside the HLH-94 or L-DEP regimens for these patients. Among the 4 patients, 1 experienced severe multiorgan dysfunction and opted to discontinue therapy. The remaining 3 patients showed controlled disease progression with significant clinical improvements following emapalumab administration. These improvements included reduced levels of inflammatory markers, normalization of blood counts and liver function, and decreased Epstein-Barr virus viral load. The findings suggest that emapalumab may be an effective and safe treatment option for pediatric EBV-HLH. However, further research is necessary to confirm these outcomes, especially in critically ill patients.

Navigating the Complexity: A Comprehensive Review of Hemophagocytic Lymphohistiocytosis Associated With Dengue Infection.

Hemophagocytic lymphohistiocytosis (HLH) associated with dengue infection presents a unique challenge in clinical practice due to its rarity, rapid progression, and overlapping clinical features. This comprehensive review navigates the complexity of HLH-dengue syndrome by examining its pathophysiology, clinical manifestations, diagnostic criteria, and therapeutic strategies. HLH, characterized by uncontrolled immune activation and cytokine dysregulation, can occur as a secondary complication of dengue infection, leading to severe multiorgan dysfunction and high mortality if not promptly recognized and treated. The review underscores the significance of early diagnosis through vigilant clinical monitoring and appropriate diagnostic tests, such as bone marrow examinations and genetic studies. Collaboration between infectious disease specialists, hematologists, and critical care teams is essential for optimal management. Despite advancements in understanding HLH-dengue syndrome, further research is needed to elucidate its underlying mechanisms and explore novel treatment approaches. This review provides insights into the clinical implications of HLH-dengue syndrome and emphasizes the importance of a multidisciplinary approach to improve patient outcomes in this challenging clinical scenario.

Phenotypic changes in immune cells induced by granulocyte and monocyte adsorptive apheresis in patients with severe COVID-19: An exvivo study.

SARS-CoV-2 causes systemic immune dysfunction, leading to severe respiratory dysfunction and multiorgan dysfunction. Granulocyte and monocyte adsorptive apheresis (GMA) therapy is designed to regulate an excessive inflammatory response and has been proposed as a potential therapeutic strategy for coronavirus disease 2019 (COVID-19). We aimed to investigate a targeted subset of granulocytes and monocytes to be removed after GMA therapy in patients with severe COVID-19 infection. We established an exvivo experimental system to study the effects of GMA. Blood samples were collected into EDTA-treated tubes and a mixture of blood samples and cellulose acetate beads was used in GMA. After GMA, blood samples were removed, and the granulocyte and monocyte subtypes before and after GMA were determined by CyTOF mass cytometry. To analyze mass cytometry data with a self-organizing map, hierarchical clustering was used to determine the appropriate number of metaclusters from t-distributed stochastic neighbor embedding. We included seven patients with severe COVID-19 and four age- and sex-matched volunteers. Granulocyte subsets removed by GMA strongly expressed CD11b, CD16, and CD66b, and weakly expressed CD11c, consistent with mature and activated neutrophils. Monocyte subsets strongly expressed CD14, weakly expressed CD33 and CD45RO, and did not express CD16. These subsets were indicated to promote the release of inflammatory cytokines and activate T cells. The identification of the granulocyte and monocyte subsets removed after GMA in patients with severe COVID-19 may help explain the potential mechanism underlying the effectiveness of GMA in COVID-19 and other inflammatory diseases.

EMERGENCE OF A TECHNOLOGY-DEPENDENT PHENOTYPE OF PEDIATRIC SEPSIS IN A LARGE CHILDREN'S HOSPITAL.

Objective: To investigate whether pediatric sepsis phenotypes are stable in time. Methods: Retrospective cohort study examining children with suspected sepsis admitted to a Pediatric Intensive Care Unit at a large freestanding children's hospital during two distinct periods: 2010-2014 (early cohort) and 2018-2020 (late cohort). K-means consensus clustering was used to derive types separately in the cohorts. Variables included ensured representation of all organ systems. Results: One thousand ninety-one subjects were in the early cohort and 737 subjects in the late cohort. Clustering analysis yielded four phenotypes in the early cohort and five in the late cohort. Four types were in both: type A (34% of early cohort, 25% of late cohort), mild sepsis, with minimal organ dysfunction and low mortality; type B (25%, 22%), primary respiratory failure; type C (25%, 18%), liver dysfunction, coagulopathy, and higher measures of systemic inflammation; type D (16%, 17%), severe multiorgan dysfunction, with high degrees of cardiorespiratory support, renal dysfunction, and highest mortality. Type E was only detected in the late cohort (19%) and was notable for respiratory failure less severe than B or D, mild hypothermia, and high proportion of diagnoses and technological dependence associated with medical complexity. Despite low mortality, this type had the longest PICU length of stay. Conclusions: This single center study identified four pediatric sepsis phenotypes in an earlier epoch but five in a later epoch, with the new type having a large proportion of characteristics associated with medical complexity, particularly technology dependence. Personalized sepsis therapies need to account for this expanding patient population.

Exploratory Analyses of Lymph Node Tissue, Serum, and Peripheral Blood Mononuclear Cells Do Not Reveal Pathogen Signatures in Idiopathic Multicentric Castleman Disease

Background : Castleman disease (CD) encompasses a group of hematologic disorders that share characteristic histopathological features. Unicentric CD (UCD) involves a solitary enlarged lymph node with typically mild symptoms. Multicentric CD (MCD) involves generalized lymphadenopathy and often severe cytokine-driven multi-organ dysfunction. MCD is further subdivided into cases caused by Human Herpesvirus-8 (HHV-8-associated MCD) infection, POEMS syndrome (POEMS-associated MCD), and those with an idiopathic cause (iMCD). The underlying pathological mechanisms and etiologies of UCD and iMCD are not well understood. Given that a viral pathogen, HHV-8, causes HHV-8-associated MCD, we pursued multiple approaches to identify potential pathogens that may trigger iMCD and UCD. Methods: We used 2 distinct detection methods to identify potential pathogens in CD. PathoChIP is a microarray-based assay that uses ~60,000 DNA/RNA probes to detect 4,000+ pathogens associated with human diseases. Viral Track is a computational method that can be applied to unmapped next-generation sequencing (NGS) reads to search for the presence of viral RNA. Formalin-fixed paraffin-embedded (FFPE) lymph node tissue was analyzed by PathoChIP from iMCD (n=6), UCD (n=8), HHV8-associated MCD (n=1, HHV8-MCD), EBV-driven post-transplant lymphoproliferative disorder (n=1, EBV-PTLD), reactive samples without a clear etiology (n=1), and POEMS-associated MCD (n=2) patients. We also analyzed serum from iMCD patients (n=2) and healthy donors (n=8). A ‘positive’ probe for a given microorganism was defined as exceeding the 95 th percentile on a per-probe basis of the optical signal captured across all probes in the dataset. Data from single-cell RNA sequencing of cryopreserved peripheral blood mononuclear cells (iMCD, n=4; EBV, n=2; HHV8, n=1; healthy donor, n=2) and bulk RNA sequencing of FFPE lymph node tissue (iMCD, n=9; sentinel, n=7; systemic lupus erythematosus (SLE), n=3; Diffuse large B-cell lymphoma (DLBCL), n=3) were used as input into the Viral Track program. To detect a positive viral signal, standard thresholds were required: &amp;gt;50 uniquely mapped reads to a given virus, a read complexity threshold &amp;gt;1.2, and &amp;gt;10% coverage of the length of the respective viral genome. Results: After quality control, 49,657 probes from the PathoCHIP assay were mapped to 4,000+ known pathogens. As expected, the HHV-8 MCD and EBV-PTLD samples identified significantly more positive probes compared to the rest of the cohort for HHV-8 (65/259 vs 1/259) and EBV (38/235 vs 1/235), respectively. Importantly, no other microorganisms were detected in UCD or MCD lymph nodes or serum samples at a significantly increased rate than controls. For Viral Track, human endogenous retrovirus K113 and Escherichia phages were detected at low levels throughout all results. Excluding these viruses, positive controls including HHV-8-MCD, and EBV solely identified their respective predicted virally mapped NGS reads and no viral signature was detected in healthy donors. Importantly, there was no significant viral signature specific to CD in PBMCs or LN tissue. Interestingly, 1 iMCD sample did contain a significant number of NGS sequencing reads mapping to HHV5. These results were confirmed with clinical data reporting a positive IgG, negative PCR, and negative IgM test within 2 weeks of the biopsy date, suggesting that the HHV5 positive result was likely detecting a previous, now latent infection rather than a potential pathological driver of CD. Conclusions: Although there are limitations to this study, including small cohorts and viral mRNA single-cell capture limitations, we were able to use 2 orthogonal pathogen detection methods on multiple tissue types from iMCD patients. Taken together, our results suggest that an active infectious agent is unlikely to be a major contributor or pathological mechanism driving UCD or iMCD. The continued search for potential causative microorganisms in iMCD patients should continue, but our results suggest that alternative hypotheses related to the pathology and etiology of iMCD and UCD should be prioritized.

Prognostic value of ECG monitor findings in COVID-19

AimsCOVID-19 can cause severe illness and multiorgan dysfunction. Acute myocardial damage has been detected in a significant portion of patients with COVID-19; therefore, several studies have reported that electrocardiographic findings...

Procalcitonin is elevated in severe malaria and is a promising biomarker of severe malaria and multi-organ dysfunction: A cross-sectional study and meta-analysis

BackgroundElevated procalcitonin (PCT) has been reported in bacterial infection and is positively associated with the severity of the disease. Patients with severe Plasmodium falciparum malaria also display higher procalcitonin levels compared to those with non-severe disease, indicating a possible role for bacterial infection in severe disease, however this observation remained variable in different study population. Furthermore, the significance of PCT in different clinical categories of severe malaria has not been evaluated so far. MethodsA total of 74 P. falciparum-infected subjects were enrolled in the study comprising of 55 cases complicated malaria [cerebral malaria- 14; non-cerebral severe malaria- 21; multi-organ dysfunction- 20] and 19 uncomplicated cases. Serum levels of PCT were quantified by fluorescence immunoassay. For meta-analysis, the literature search was performed in different databases, and all relevant articles were screened, and eligible reports were identified based on predefined inclusion and exclusion criteria. The meta-analysis was performed by comprehensive meta-analysis software V3 and MedCalc 20.218. ResultsPatients with severe P. falciparum malaria had significantly higher PCT levels compared to uncomplicated cases (p = 0.01). Analysis of PCT in different categories of patients with severe malaria revealed significantly elevated PCT in multi-organ dysfunctions compared to those with uncomplicated malaria (p = 0.004) and cerebral malaria (p = 0.05). Interestingly the receiver operating characteristics curve analysis showed procalcitonin as a promising biomarker for differentiating severe malaria (AUC: 0.697, p = 0.01) and multi-organ dysfunction (AUC: 0.704, p = 0.007) from uncomplicated malaria and other clinical categories of falciparum malaria, respectively. Furthermore, meta-analysis also revealed an elevated procalcitonin in severe malaria and it could be an important biomarker in the management of severe disease. ConclusionsPCT is elevated in P. falciparum-infected patients and could be a good biomarker for diagnosis of severe malaria and multi-organ dysfunction. It can help in the management of severe disease with additional treatment options.

Marburg virus disease: lesson learned from the first outbreak encounter in Tanzania

Marburg virus disease: lesson learned from the first outbreak encounter in Tanzania

Evaluating the Efficacy of a Small Interfering Ribonucleic Acid Molecule, Givosiran, in Treating Acute Intermittent Porphyria: A Systematic Review.

Acute intermittent porphyria (AIP) is a severe multiorgan dysfunction disorder that can be fatal if not treated promptly. The newest treatment modality involving small interfering RNA (siRNA) molecules, givosiran, is administered for AIP. Although it has very beneficial effects in treating attacks of AIP, it comes with an extensive side effect profile that is not fully understood or studied. Hence, this novel drug model treatment's risk-benefit evaluation is still necessary. For relevant medical literature, we explored medical databases such as PubMed/Medline, PubMed Central, Cochrane Library, Internet Archive Scholar, Google Scholar, and Wiley Online Library. The selected papers were screened based on eligibility criteria and filtered through quality appraisal tools, and 13 finalized research papers were included in the study. Of the 13 identified papers, three were clinical trials, and 10 were review articles. The selected papers all discussed the effectiveness and side effects of givosiran in acute and recurrent attacks of AIP. The research papers showed decreased rates of acute attacks of AIP with givosiran and terminating recurrent attacks. But there are certain non-serious side effects, like fatigue and nausea. Also, there are some severe side effects, like pain. There is limited information on renal and liver function impairment using givosiran and the use of givosiran in patients with kidney and liver disease, for which further studies are required.

Associations between IL-17A G/A-rs2275913 and IL 23R A/G-rs11209026 gene polymorphisms and severe coronavirus disease 2019 (COVID-19)

Severe COVID-19 disease was linked to a severe proinflammatory response and cytokine storm interleukin 17 (IL-17) is one of these cytokines, was associated with severe acute lung injury and multiorgan dysfunction. Single nucleotide polymorphisms (SNPs) in genes coding IL-17 can affect level of IL-17 hence its role in diseases. Also, SNPs in IL-23 R which control IL-23 is the main activator of IL-17 production. This study aimed to determine whether the IL-17A (G/A-rs2275913), IL-23R (A/G rs11209026) SNPs and serum levels of IL-17 were related to the risk of severe COVID-19. This case-control study included 120 confirmed COVID-19 patients, divided into two categories according to the severity of the disease and 74 normal subjects as controls. COVID-19 patients were SARS-CoV-2 positive by a reverse transcription-polymerase chain reaction and subjected to full clinical examinations, routine laboratory tests, and radiographic evaluations. The IL-17 levels were assessed using ELISA method, and genotyping of IL-17A (197 A/G; rs2275913) and IL-23R rs11209026 (A/G) was performed by the TaqMan Genotyping Assay. There were no differences in the distribution of IL-17A or IL-23R genotypes between COVID-19 groups and the control group (p=0.93 and p=0.84, respectively). Severe COVID-19 patients had significantly higher IL-17 serum levels than non-severe COVID-19 (p=0.0001). The GG genotypes of IL-17A were significantly higher in severe COVID-19 patients (p=0.004). Multivariate logistic regression analysis revealed that AG, GG genotypes of IL-17 and IL-17A were independent predictors of COVID-19 disease severity (p < 0.0001, p=0.06 and p=0.04, respectively). ROC curve analysis for IL-17, as predictor of severe COVID-19 disease revealed a sensitivity of 87.9% and specificity of 66.1% at a cutoff point of 114 pg/ml with AUC = 0.799. In conclusion, these findings indicated that IL-17 may be considered a marker of severe COVID-19. IL-17A SNPs may have a role in COVID-19 severity. IL-23R SNPs had no role in COVID-19.

Investıgatıon of the Effects of Favipiravir and Oseltamivir Active Substances Used in the Treatment of Covid-19 on Carbonic Anhydrase I-II Isoenzymes and Acetylcholine Enzyme Activities in Vitro

Covid-19, originating from Wuhan, China, is a worldwide health problem. Immune system abnormalities caused by covid-19 lead to infections, septic shock, and severe multi-organ dysfunction. The drugs used for treatment are palliative pharmacological alternatives and help manage symptoms or complications that occur during the course of the disease. Both carbonic anhydrases and cholinesterases can be target enzymes for drugs. The goal of this study is to determine how the drugs used in covid-19 affect patients being treated for Alzheimer's disease, myasthenia gravis, glaucoma, or epilepsy, and to determine if there are drug-drug interactions. In case of possible interactions, it is crucial for these patients to consider alternative treatments and to recheck the dosage of the drugs used. To this end, the effects of the drugs favipiravir and oseltamivir, which are used in the covid-19 clinic and whose relationship with these enzymes has not been previously studied, on the isoenzymes of carbonic anhydrase I- II and the enzyme acetylcholinesterase were studied in vitro. No inhibition or activation was observed on the enzyme acetylcholinesterase, while inhibition was observed for the isoenzyme carbonic anhydrase I - II.

Acute Left Heart Failure in the Emergency Room

Acute heart failure (AHF), a rapid or gradual onset of symptoms and/or signs of heart failure severe enough for the patient to seek urgent medical attention, represents a significant and growing healthcare burden. With a prevalence of approximately 1%–2% of the adult population, over 5 million Americans and 15 million Europeans, with a yearly incidence of 550,000, rising ≥ 10% among the elderly. Despite therapeutic advances in chronic heart failure, the prognosis of AHF is poor, with in-hospital mortality ranging from ~2% in hypertensive AHF up to 40-60% in patients with cardiogenic shock, which is a life-threatening state characterized by tissue hypoperfusion resulting in severe multi-organ dysfunction and death. Although no current therapeutic approach has improved mortality in this patient population, incorporating standardized, multidisciplinary shock teams may change. In addition, correct and expedited identification and management of AHF can be challenging due to the heterogenicity of its clinical presentation, precipitant factors, and comorbid conditions. Thus, clinicians involved in patient care should perform a structured diagnostic work-up, starting with high clinical suspicion, followed by key diagnostic tests, including biomarkers, lung ultrasonography, and echocardiography, allowing recognition of the different clinical and hemodynamic profiles and providing guidance to perform further tests and therapeutic interventions. This review discusses the healthcare burden of acute heart failure, highlights the importance of its expedited recognition, and details a proposed diagnostic work-up and individualized management approach in the emergency department. We also perform a concise review of current international guideline recommendations. Future research directions are also provided.

Antibiotic treatment for infection with Shiga toxin producing Escherichia coli infection inducing a hemolytic uremic syndrome

Background: Shiga toxin producing Escherichia coli (STEC) inducing hemolytic uremic syndrome (HUS) with multiple organ involvement is associated with significant morbidity and mortality. The treatment has mostly been focused on kidney, respiratory and cardiovascular supports and not against the bacteria that cause STEC-HUS. The use of bactericidal therapy has been shown to be antibiotic dependent and certain antibiotics inhibit the production and release of Shiga toxin, eradicate STEC without harmful effects, and improve outcome. Methods: A previously healthy 18-months-old girl with STEC causing severe colitis, kidney failure and multi-organ dysfunction was treated with antibiotics that were known to inhibit the release of Shiga toxin as a supplement to supportive care. Results: The antibiotic regime stopped the pathophysiological process with prompt clinical improvement in association with the disappearance of the Shiga toxins. Conclusions: The present case report fortifies and recommends appropriate antibiotic treatment during STEC-HUS, suggesting clinicians to consider the use of these in severe STEC-HUS as early as possible.

617: CANNABIDIOL GUMMY INGESTION LEADING TO CARDIAC ARREST IN A PEDIATRIC PATIENT

Introduction: Rising popularity and availability of cannabidiol (CBD) products have led to increased accessibility in homes. The resemblance of CBD gummies to candy has led to unintentional ingestions in pediatric patients. Toxic doses of CBD are unknown, and contamination with other cannabinoids and toxins can occur. Few reports describe CBD toxicity. Respiratory and neurologic depression are the main effects. Description: A 4-year-old 60kg male with a voracious appetite was found unresponsive at home. Parents report he ate half a 75mg CBD gummy approximately 6 hours prior to the event. At EMS arrival rhythm was a wide ventricular complex. At ED arrival the child remained pulseless with active cardiopulmonary resuscitation. Return of spontaneous circulation was obtained after approximately 20 minutes of downtime, though in a wide complex tachycardia. Labs demonstrated severe metabolic acidosis, hyperkalemia, and multiorgan dysfunction. Head CT showed diffuse cerebral edema and effacement of the sulci and basal cisterns. Shortly after transfer to our tertiary care center PICU he developed unequal pupils and received hyperosmolar therapies. He had no cough and no gag, corneal or pupillary reflexes. Electroencephalography demonstrated burst suppression pattern. Norepinephrine and epinephrine were started for hypotension. Echocardiogram showed poor biventricular function. Genetic testing for cardiomyopathies and arrhythmias was sent given the presenting rhythm. Given the neurologic exam and poor prognosis the family elected to withdraw life-sustaining therapies. A serum drug analysis was negative. A comprehensive urine drug analysis resulted 4 days later with carboxy-tetrahydrocannabinol (THC) >14,286 ng/mL, suggesting consumption of a substantial amount of CBD gummies containing THC. Discussion: The majority of CBD products are unregulated and can contain other cannabinoids, toxins, or synthetic equivalents, as shown in this case. CBD and synthetic equivalents do not result on traditional toxicology screens. Further testing may not be readily available, posing a diagnostic dilemma for practitioners. This case highlights the importance of considering CBD intoxication in patients who present with acute neurologic, respiratory, and cardiovascular depression.

A Case of Neonatal Lupus Presenting with Myocardial Dysfunction in the Absence of Congenital Heart Block (CHB): Clinical Management and Brief Literature Review of Neonatal Cardiac Lupus

Neonatal lupus (NLE) is a rare acquired autoimmune disorder caused by transplacental passage of maternal autoantibodies to Sjogren’s Syndrome A or B (SSA-SSB) autoantigens (Vanoni et al. in Clin Rev Allerg Immunol 53:469–476, 2017) which target fetal and neonatal tissues for immune destruction. The cardiac trademark of NLE is autoimmune heart block, which accounts for more than 80% of cases of complete atrioventricular heart block (AVB) in newborns with a structurally normal heart (Martin in Cardiol Young 24: 41–46, 2014). NLE presenting with cardiac alterations not involving rhythm disturbances are described in the literature, but they are rare. Here, we report a case of a neonate with high anti-SSA antibodies who developed severe ventricular dysfunction in the absence of rhythm abnormalities, endocardial fibroelastosis, and dilated cardiomyopathy (Trucco et al. in J Am Coll Cardiol 57:715–723, https://doi.org/10.1016/j.jacc.2010.09.044, 2011), the most common cardiac presentations of NLE. The patient developed severe multiorgan dysfunction syndrome that required prolonged critical care support but fully recovered and was discharged home. We highlight the unusual clinical features of this NLE case and the importance of timely treatment of NLE allowing complete recovery of a critically ill neonate.