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Abstract: Metformin (MTF) is a widely used oral antidiabetic medication. Regardless the reason, high doses of MTF cause lactic acidosis as a result of its effects on mitochondrial ATP production and no-mediated vascular smooth muscle relaxation. Metformin-associated lactic acidosis can be life-threatening despite all treatments. Methylene blue (MB) has the potential to reverse the toxic effects of MTF through its effects on both the mitochondrial respiratory chain and nitric oxide production. The use of MB in MTF intoxication has only been reported in a limited number of cases. Herein, we present a 16-year-old female patient who attempted suicide by ingesting high doses of MTF. Supportive treatments, such as vasopressor, inotropic treatments, and sodium bicarbonate, were started in the patient who developed fluid-resistant hypotension after pediatric intensive care unit admission. Because of rising lactate levels, Continuous renal replacement therapy (CRRT) was started immediately. Despite all treatments, hypotension and hyperlactatemia persisted; MB was given as a rescue therapy. Noticeable hemodynamic improvement was observed within 30 minutes of initiating MB infusion, allowing a gradual decrease in the doses of inotropic infusions within the first hour of therapy. Patient's cardiovascular support was discontinued on the second day, and she was discharged on the fifth day. We speculate that, considering the mechanisms of MTF toxicity and the mechanisms of action of MB, it is suggested that early administration of MB, not only as a rescue treatment but as the initial approach to MTF poisoning in combination with other treatments, may result in improved outcomes., Competing Interests: Disclosure: The author declares no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Hepatic veno-occlusive disease (VOD) is a critical medical emergency with a high mortality rate of up to 90% if not promptly treated. Defibrotide is the only approved medication for VOD treatment, exhibiting anti-inflammatory, antithrombotic, and anti-ischemic properties. This report presents a case of severe VOD in a patient undergoing acute lymphoblastic leukemia (ALL) treatment., Case Presentation: We describe the successful and rapid treatment of severe VOD in an ALL patient using therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and methylprednisolone (MPZ). The patient showed significant clinical and laboratory improvement after this combined therapeutic approach., Conclusion: This case highlights the effectiveness of TPE, IVIG, and MPZ in the treatment of severe VOD in ALL patients, providing insights into alternative therapeutic strategies in the absence of Defibrotide., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Calcium-channel blocker (CCBs) intoxication remains the most lethal among all other drug overdoses (Arroyo and Kao. Pediatr Emerg Care 2009;25:533-538). This study aimed to describe the use and efficacy of intravenous lipid emulsion treatment in our CCB overdose patients in tandem with a comprehensive literature investigation., Case Reports: Hereby we report 4 adolescent patients who arrived to the pediatric emergency department after intentional CCB ingestions. All patients were hospitalized in pediatric intensive care unit because of hypotension, and they were initially treated with fluid boluses, glucagon, calcium infusion, vasopressors, inotropes and insulin. Intravenous lipid emulsion (dose: 20% lipid emulsion given as a 1.5-mL/kg bolus followed by 0.25-0.5 mL/kg/min for 30-60 minutes) treatment was given to all patients unresponsive to initial treatments. Hemodynamic instability improved immediately after intravenous lipid emulsion treatment. All patients were discharged with complete recovery at the sixth day of pediatric intensive care unit admission., Conclusions: Intravenous lipid emulsion therapy stands as a salvage treatment for CCB intoxications with cardiovascular failure unresponsive to standard supportive treatments., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Multisystem inflammatory syndrome in children (MIS-C) can be life threatening in severe cases because of uncontrolled inflammation and multi-organ failure. In this study, we report the effect of plasma exchange in the treatment of MIS-C and to emphasize the effect of its early application on outcome., Method: In this retrospective observational study, the medical records of children with severe MIS-C admitted to pediatric intensive care unit (PICU) between April 2020 and January 2021 were reviewed. Severe MIS-C patients were treated according to protocol consisting of plasma exchange (PE), intravenous immune globulin, steroids, and anakinra which we called the "PISA" protocol referring to the initials. The patients were divided into two groups as early plasma exchange (E-PE) and late plasma exchange (L-PE) according to the elapse time between hospital admission and the administration of PE. Groups were compared in terms of outcome variables. Primary study outcome was 28-day mortality. Secondary outcome variables were acute phase response time, length of immunomodulatory treatment, frequency of patients requiring mechanical ventilation (MV) and inotropic support, length of inotropic support and MV, length of hospital and PICU stays., Results: Eighteen pediatric patients with MIS-C were included in the study. Seventeen (95%) of the patients presented with decompensated shock and required inotropic support. One of the 17 patients needed extracorporeal membrane oxygenation support (ECMO) PISA protocol was used in all patients. There was no mortality in the E-PE group while the mortality rate was 20% in the L-PE group. Acute phase reactant response was faster in the E-PE group and immunomodulatory treatments could be reduced earlier; the frequency of patients requiring inotropic and mechanical ventilation (MV) support was lower in the E-PE group; the duration of inotropic support, duration of MV, and length of stay in hospital and PICU were significantly shorter in the E-PE group., Conclusion: We suggest that in selected cases, timely administration of PE is a beneficial rescue therapy for MIS-C related hyperinflammation presenting with severe cardiovascular collapse., (© 2022 Wiley Periodicals LLC.)

Background: Extracorporeal membrane oxygenation (ECMO) can be associated with severe neurological complications increasing morbidity and mortality. We aimed to evaluate imaging findings in patients with neurological complications associated with ECMO., Methods: Children ( < 18 years) who had ECMO support and received cross-sectional imaging (cranial CT and/ or MRI) were retrospectively evaluated. Age, gender, clinical and imaging findings were documented and the relation to ECMO duration and survival rates with imaging findings and imaging time (during ECMO or after weaning) were examined., Results: Twenty children who had cranial CT/MRI during (n=6) ECMO and after weaning (n=14) were included in the study. The median duration of ECMO was 12.5 days (IQR=5-25 days) with a survival rate of 65%. Fourteen patients had positive imaging findings including ischemic stroke (n=4), hemorrhagic stroke (n=4), hypoxicischemic encephalopathy (n=2), posterior reversible encephalopathy syndrome (PRES) (n=3) and cerebral vein thrombosis (n=1). The duration of ECMO and survival rates did not significantly differ between patients with positive and unremarkable imaging findings. However, the survival rate was significantly higher (p < 0.001) and the duration of ECMO was significantly lower in patients scanned after weaning compared to patients imaged during ECMO support (p=0.033)., Conclusions: Our series revealed PRES in ECMO-related neurologic events in addition to commonly reported thrombotic and hemorrhagic stroke in the literature. Availability of cross-sectional imaging and awareness of radiologists to these complications during ECMO or after weaning help in prompt diagnosis and treatment.

Objective: We aimed to describe the typical clinical and laboratory features and treatment of children diagnosed with multisystem inflammatory syndrome in children (MIS-C) and to understand the differences as compared to severe/critical pediatric cases with COVID-19 in an eastern Mediterranean country., Methods: Children (aged <18 years) who diagnosed with MIS-C and severe/critical pediatric cases with COVID-19 and were admitted to hospital between March 26 and November 3, 2020 were enrolled in the study., Results: A total of 52 patients, 22 patients diagnosed with COVID-19 with severe/critical disease course and 30 patients diagnosed with MIS-C, were included in the study. Although severe COVID-19 cases and cases with MIS-C share many clinical and laboratory features, MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe cases (p<0.001 for each). Of all, 53.3% of MIS-C cases had the evidence of myocardial involvement as compared to severe cases (27.2%). Additionally, C-reactive protein (CRP) and white blood cell (WBC) are the independent predictors for the diagnosis of MIS-C, particularly in the existence of conjunctival injection and rash. Corticosteroids, intravenous immunoglobulin (IVIG), and biologic immunomodulatory treatments were mainly used in MIS-C cases rather than cases with severe disease course. There were only three deaths among 52 patients, one of whom had Burkitt lymphoma and the two cases with severe COVID-19 of late referral., Conclusion: Differences between clinical presentations, acute phase responses, organ involvements, and management strategies indicate that MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19. Conjunctival injection and higher CRP and low WBC count are reliable diagnostic parameters for MIS-C cases. Key Points • MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe/critical pediatric cases with COVID-19. • Higher CRP and low total WBC count are the independent predictors for the diagnosis of MIS-C. • MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19., (© 2021. International League of Associations for Rheumatology (ILAR).)

Unlabelled: Pressure-induced urticaria is a non-immunoglobulin E-mediated type of urticaria. Some patients only have angioedema, and the term pressure-induced angioedema (PIA) is more appropriate for them. PIA has not previously been reported in association with endotracheal tube. Here we describe two patients who developed PIA after endotracheal intubation. There were no histories of angioedema, drug and food allergy in both patients. Tests for specific aero-allergens and latex were negative. Serum total immunoglobulin E and C4 levels were in normal ranges. Antihistamines and intravenous steroid therapy were ineffective. Angioedema regressed with intravenous epinephrine infusion and did not relapse after extubation., Conclusion: We suggest that endotracheal tubes can cause PIA. Epinephrine therapy should be used early at treatment, especially in the patients who are at great risk for life-threatening airway problems.