Cytokine elimination in suspected COVID-19 perymyocarditis

Background: Only recently studies have been able to demonstrate the safety and efficacy of purification therapies in inflammatory diseases. Here we present the management of a young (21y) male patient in severe cardiogenic shock due to COVID-19 perymyocarditis admitted to the ICU at Bolzano Central Hospital. November 30th 2020 the patient developed high fever (>40 C) and diarrhea. After unsuccessfully being treated orally with a macrolide he was admitted to a peripheral hospital the 4th of December. The day after he deteriorated, required transfer to the ICU, endotracheal intubation and pharmacological cardiovascular support (Norepinephrine, Levosimendan). Antimicrobial treatment was started with piperacillin/tazobactam, linezolid and metronidazole. Despite multiple radiological and microbiological diagnostic attempts the origin of this severe septic shock remained unclear. December 6th the patient was transferred to Bolzano Central Hospital for VA-ECMO evaluation. Method(s): The transesophageal echocardiography revealed 15-20% of EF, lactate (5,2 mmol/l), cardiac enzymes (TropT 1400 mcg/l) and inflammatory parameters (PCT 35 ng/ml, IL-6 685 pg/ml) were elevated. We performed cardiac monitoring via Swan-Ganz catheter. The cardiac index was 1,6 l/min/m2. The peak dosage for Norepinephrine reached 7,5mg/h (1,47 mcg/kg/min). At Bolzano ICU we facilitate the pharmacological therapy with milrinone, vasopressin and low dose epinephrine. Furthermore, we impost continuous hemodiafiltration with CytoSorb filter. Result(s): Only hours after the start of filtration therapy the patient improved and we were able to gradually reduce catecholamine therapy, lactate values decreased. A VA-ECMO implantation was no more necessary. December 10th, we saw a stable patient without ventilatory or cardiovascular support, at echocardiography we revealed a normal EF. Conclusion(s): Clinically we saw a young patient in severe septic/cardiogenic shock due to perimyocarditis. Yet diagnostic attempts (CT-scan, multiple blood/urinary/liquor cultures) remained negative. Despite multiple negative PCR tests for SARS-CoV2 infection we performed specific immunoglobulin analysis and received a positive result for IgM. We therefore conclude on a COVID-19 associated perymyocarditis. Furthermore, this case illustrates the potential benefit of cytokine filtration and elimination in COVID-19 patients with altered IL6 levels.

Guillain-Barre syndrome following COVID-19 vaccination: a case report and an updated review

Background: Coronavirus disease-2019 (COVID-19) has caused a pandemic that has recently affected every aspect of life. Fortunately, many vaccines with high safety and efficacy profiles were developed timely to face this pandemic. In a very short time, billions of people were vaccinated. In the meantime, a wide range of neurological syndromes are being reported. Guillain-Barre syndrome (GBS) which is a rare immune-mediated post-infectious peripheral neuropathy was reported after both the COVID-19 infection itself and many types of its vaccines. Method(s): We are reporting a case of post-AstraZeneca vaccine GBS and reviewing the literature of all reported post-COVID-19 vaccines GBS till July 2021. Result(s): 29 adult patients were reported. Of them 58.6% were males. Their mean age is 58.2 years. The median time to clinical onset after vaccine administration was 13.2 days. 86.2% of patients had their symptoms following immunization with the 1st dose of AstraZeneca vector-based covid vaccine. Facial palsy was the most predominant single symptom in 75.8% of patients. Conclusion(s): Guillain-Barre syndrome is a well-recognized but still rare adverse event following vaccination against COVID-19. Although preliminary data incriminates viral vector-based vaccines more than the other types, active post-vaccination surveillance and more powerful statistics are mandatory to reach a solid conclusion regarding the presence of a causal relation.Copyright © 2022

Review novel insights into the diagnostic and prognostic function of copeptin in daily clinical practice.

As is shown in previous reports, arginine vasopressin (AVP), as one of the most important hormones within circulation in human beings, is of great clinically significance given that it could maintain the body fluid balance and vascular tone. However, the laboratory measurements AVP in daily clinical practice are shown to be difficult and with low accuracy. Concerning on this notion, it is unpractical to use the serum levels of AVP in diagnosing multiple diseases. On the other hand, another key serum biomarker, copeptin, is confirmed as the C-terminal of the AVP precursor which could be released in equal amounts with AVP, resultantly making it as a sensitive marker of arginine vasopressin release. Notably, emerging recent evidence has demonstrated the critical function of copeptin as a clinical indicator, especially in the diagnosis and prognosis of several diseases in diverse organs, such as cardiovascular disease, kidney disease, and pulmonary disease. In addition, copeptin was recently verified to play an important role in diagnosing multiple acute diseases when combined it with other gold standard serum biomarkers, indicating that copeptin could be recognized as a vital disease marker. Herein, in the current review, the functions of copeptin as a new predictive diagnostic and prognostic biomarker of various diseases, according to the most recent studies, are well summarized. Furthermore, the importance of using copeptin as a serum biomarker in diverse medical departments and the impact of this on improving healthcare service is also summarized in the current review.

New developments and concepts in the diagnosis and management of diabetes insipidus (AVP-deficiency and resistance).

Diabetes insipidus (DI) is a disorder characterised by the excretion of large amounts of hypotonic urine, with a prevalence of 1 per 25,000 population. Central DI (CDI), better now referred to as arginine vasopressin (AVP)-deficiency, is the most common form of DI resulting from deficiency of the hormone AVP from the pituitary. The less common nephrogenic DI (NDI) or AVP-resistance develops secondary to AVP resistance in the kidneys. The majority of causes of DI are acquired, with CDI developing when more than 80% of AVP-secreting neurons are damaged. Inherited/familial CDI causes account for approximately 1% of cases. Although the pathogenesis of NDI is unclear, more than 280 disease-causing mutations affecting the AVP2 protein or AVP V2 receptor, as well as in aquaporin 2 (AQP2), have been described. Although the cAMP/protein kinase A pathway remains the major regulatory pathway of AVP/AQP2 action, in vitro data have also revealed additional cAMP independent pathways of NDI pathogenesis. Diagnosing partial forms of DI, and distinguishing them from primary polydipsia, can be challenging, previously necessitating the use of the water deprivation test. However, measurements of circulating copeptin levels, especially after stimulation, are increasingly replacing the classical tests in clinical practice because of their ease of use and high sensitivity and specificity. The treatment of CDI relies on desmopressin administration, whereas NDI requires the management of any underlying diseases, removal of offending drugs and, in some cases, administration of diuretics. A better understanding of the pathophysiology of DI has led to novel evolving therapeutic agents that are under clinical trial.

The Relationship of Hyponatremia with Il-6 and Implications on Clinical Outcomes in Covid-19 Patients Admitted at University Santo Tomas Hospital, January to August 2021

Introduction: COVID-19 is a droplet-transmitted infection with clinical manifestation ranging from mild disease to cytokine storm. The cytokine storm is an exaggerated response of the human body in which excessive amounts of inflammatory markers are released leading to multiple organ failure. In COVID-19, the most common electrolyte disorder noted is hyponatremia. Hyponatremia results from an increase in cytokines including IL-6 can result in the release of anti-diuretic hormone causing a decrease in serum sodium. Hyponatremic patients were observed to have increased risk for ICU admission, mechanical ventilation and mortality as compared to normonatremia. The inflammatory markers including serum ferritin, procalcitonin, IL-6, HsCRP, LDH, and D-dimer have been imperative as prognostic markers to help guide healthcare workers in the classification of severity, thereby guiding management. This study aims to investigate the association between serum sodium and serum IL-6 and aims to establish the role of serum sodium as an alternative cost-effective prognostic marker for COVID-19. Method(s): This is a retrospective cohort study done at the University of Santo Tomas Hospital via chart review of all confirmed COVID-19 patients admitted from January to August 2021. Data gathered included patient's age, gender, pertinent co-morbidities, day of illness on arrival, serum Na, PF ratio, chest radiograph, IL-6 levels on admission. The outcome of each case was recorded: oxygen supplementation, need for hemoperfusion, need for tocilizumab, COVID classification, days until clinical recovery, discharged, or expired. Corrected serum was used to account for effect of serum glucose on serum sodium. Serum sodium and IL-6 levels were compared to check the relationship between the two. Hyponatremia was studied in line with the poor outcomes. COVID-19 patients admitted at the COVID ward of USTH, January to August 2021 was the target population of the study. Those excluded were patients with chronic kidney disease patients, chronic hyponatremia, malignancy, uncontrolled thyroid disease, liver cirrhosis, on diuretics, with gastrointestinal losses and incomplete records. [Formula presented] Results: Of the 322 admitted COVID-19 patients, 154 were included with 89 (58%) having poor outcomes. Hyponatremia was seen in 60 (38.9%) of the population while 48 (53.93%) had poor outcomes. Serum sodium and IL-6 have an inverse relationship is not statistically significant. Patients with hyponatremia were 4.46 times more likely to require high oxygen support, 4.16 times more likely to need hemoperfusion, and 60.71% times more likely to have ICU admission. Hyponatremia was shown to have a 94.12% likelihood need for tocilizumab, 3.87 times more likely to result in severe or critical COVID-19 and 3.78 times more likely to expire. Overall, hyponatremia was 5.17 times more likely to have poor clinical outcome in comparison to normonatremia. Conclusion(s): Serum sodium cannot replace serum IL-6 as an inflammatory marker, but could be considered as a potential prognostic marker for COVID-19 when inflammatory markers are not available. COVID-19 patients with hyponatremia have a higher predisposition to increased disease severity. Including serum sodium in scoring systems could help signal to the health care providers that a more aggressive treatment approach would be indicated, thus aiding physicians in managing patients more effectively. No conflict of interestCopyright © 2023

Influenza a Myocarditis Vs Multisystem Inflammatory Syndrome Causing Cardiogenic Shock in a 34-Year-Old

Background Cardiogenic shock is a rare complication of influenza myocarditis and multisystem inflammatory syndrome. We present the case of a 32-year-old female in cardiogenic shock who met criteria for both entities. Case A 34-year-old female with hypothyroidism presented after being found down and covered in feces. She had cough and weakness the preceding days. She was febrile and hypotensive. Point of care ultrasound showed severe biventricular dysfunction and she was started on norepinephrine. She was influenza A positive with a lactate of 5.1. Right heart catheterization on 2ug/kg/min of norepinephrine showed a cardiac index (CI) of 2.82 L/min/m2 and a systemic vascular resistance (SVR) of 300 dynes/sec/cm-5. She was started on vasopressin, stress dose steroids, and oseltamivir. She received 6 amps of bicarbonate with aggressive electrolyte repletion. CI as per the Fick equation was within normal limits but lactate continued to rise. Thermodilution showed a CI of 1.6 L/min/m2 and an SVR of 2200 dynes/sec/cm-5, indicating mixed cardiogenic and distributive shock. The patient developed severe abdominal pain and was found to have elevated COVID-19 spike domain and nucleocapsid antibodies, meeting criteria for multisystem inflammatory syndrome (MIS-A). Decision-making The patient was started on dobutamine after thermodilution showed decreased CI. Intravenous immunoglobulin was started after meeting criteria for MIS-A. Her pressor requirements were weaned and then her dobutamine requirements. Follow up cardiac MRI showed mild global hypokinesis of the left ventricle and subtle hypokinesis of the right ventricular inferior wall. Left ventricular ejection fraction was 51%. The patient's cardiac MRI findings were not specific. However, her rapid improvement was suggestive of MIS-A. Additionally, consistent discordance between Fick and thermodilution resulted in confusion regarding optimization of pressors and inotropes. Conclusion The patient responded to dobutamine and MIS-A treatment after an initial impression of myocarditis. Infectious processes should be considered in any patient with new onset heart failure.Copyright © 2023 American College of Cardiology Foundation

Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial.

PURPOSE: Methylene blue (MB) has been tested as a rescue therapy for patients with refractory septic shock. However, there is a lack of evidence on MB as an adjuvant therapy, its' optimal timing, dosing and safety profile. We aimed to assess whether early adjunctive MB can reduce time to vasopressor discontinuation in patients with septic shock. METHODS: In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo. Primary outcome was time to vasopressor discontinuation at 28 days. Secondary outcomes included vasopressor-free days at 28 days, days on mechanical ventilator, length of stay in ICU and hospital, and mortality at 28 days. RESULTS: Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo. The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59-83] vs 94 h [IQR 74-141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group. Days on mechanical ventilator and mortality were similar. There were no serious adverse effects related to MB administration. CONCLUSION: In patients with septic shock, MB initiated within 24 h reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days. It also reduced length of stay in ICU and hospital without adverse effects. Our study supports further research regarding MB in larger randomized clinical trials. Trial registration ClinicalTrials.gov registration number NCT04446871 , June 25, 2020, retrospectively registered.

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

CONTEXT: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy. OBJECTIVE: To evaluate safety and efficacy of intranasal carbetocin in PWS. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up. SETTING: Twenty-four ambulatory clinics at academic medical centers. PARTICIPANTS: A total of 130 participants with PWS aged 7 to 18 years. INTERVENTIONS: Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose. MAIN OUTCOME MEASURES: Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C). RESULTS: Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing. CONCLUSIONS: Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS. CLINICAL TRIALS REGISTRATION NUMBER: NCT03649477.

Using Neuroscience-informed Group Work with Children and Adolescents Affected by the Pandemic

The COVID-19 pandemic has resulted in many types of disruptions from mild inconveniences to deaths. These disruptions have resulted in a host of stress responses among children and adolescents. Small group work is one way that helpers in schools and agencies can address developmental and diagnostic issues that arise. Neuroscience informs counselors understanding of stress responses and reactions in children and adolescents, as well as aids in generating activities and activating group therapeutic factors. This article describes the ways the neuroscience of pandemic stress and therapeutic factors can be used in group work with children and adolescents.

Transient diabetes insipidus in critically ill COVID19 patients.

PURPOSE: Vasopressin has become an important vasopressor drug while treating a critically ill patient to maintain adequate mean arterial pressure. Diabetes insipidus (DI) is a rare syndrome characterized by the excretion of a large volume of diluted urine, inappropriate for water homeostasis. We noticed that several COVID19 patients developed excessive polyuria suggestive of DI, with a concomitant plasma sodium-level increase and/or low urine osmolality. We noticed a temporal relationship between vasopressin treatment cessation and polyuria periods. We reviewed those cases to better describe this phenomenon. METHODS: We retrospectively collected COVID19 ECMO patients' (from July 6, 2020, to November 30, 2021) data from the electronic medical records. By examining urine output, urine osmolality (if applicable), plasma sodium level, and plasma osmolality, we set DI diagnosis. We described the clinical course of DI episodes and compared baseline characteristics between patients who developed DI and those who did not. RESULTS: Out of 37 patients, 12 had 18 episodes of DI. These patients were 7 years younger and had lower severity scores (APACHE-II and SOFA). Mortality difference was not seen between groups. 17 episodes occurred after vasopressin discontinuation; 14 episodes were treated with vasopressin reinstitution. DI lasted for a median of 21 h, with a median increase of 14 mEq/L of sodium. CONCLUSIONS: Temporary DI prevalence after vasopressin discontinuation in COVID19 ECMO patients might be higher than previously described for vasopressin-treated patients.

USE OF POINT-OF-CARE ULTRASONOGRAPHY (POCUS) TO PREVENT DILTIAZEM-INDUCED CARDIOGENIC SHOCK

SESSION TITLE: Using Imaging for Diagnosis Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Point of care ultrasonography (POCUS) uses an ultrasound technique that helps physicians augment physical examination findings and guide clinical decision-making at the bedside. We present a case that became a watershed moment for internal medicine residents at Abington Jefferson Hospital to use POCUS for every patient with atrial flutter/fibrillation with RVR prior to initiating diltiazem drip. CASE PRESENTATION: A 73-year-old male presented to the emergency department with complaints of palpitations. He was tachycardic with a heart rate in the 150s, and his rhythm was irregular. His basic labs were normal;an electrocardiogram investigation showed that he was experiencing an atrial flutter with 2:1 and 3:1 blocks. Chest X-ray was clear. He was given IV metoprolol 10 mg twice without achieving rate control and then started on a diltiazem drip, which initially improved his heart rate to 70s with rhythm changing to atrial flutter with 4:1 block. However, he started to become hypoxic, requiring intubation and then hemodynamically unstable, requiring initiation of pressors. Postintubation CXR indicated bilateral diffuse pulmonary edema and vascular congestion. Subsequently, he had Pulseless electrical activity (PEA) arrest. Return of spontaneous circulation (ROSC) was achieved after 3 minutes of chest compression and one round of epinephrine injection. Transthoracic echocardiogram showed an ejection fraction of 10%. He had a right heart catheterization which showed a CI of 1.7 and elevated PCWP and RVP. He was started on milrinone for ionotropic support and needed norepinephrine, vasopressin and phenylephrine to sustain his blood pressure. DISCUSSION: Atrial flutter and fibrillation are routinely seen arrhythmias in hospital settings. Patients with irregular rhythm who are in rapid ventricular rate and normotensive are often given IV metoprolol few times and then started on a diltiazem drip if RVR continues. Diltiazem not only decreases heart rate (negative chronotropic) but also decreases ventricular squeeze (negative ionotropic). It is contraindicated in patients with reduced ejection fraction. Patients’ ejection fraction values are not always known, especially if they have never had a transthoracic echocardiogram in the past or prior records are not available. POCUS helps physicians and residents to access and estimate LV function quickly and augments clinical decision making at the bedside. CONCLUSIONS: Internal Medicine Residents at Abington Hospital have made it a part of their protocol to always perform bedside ultrasonography in patients with atrial flutter/fibrillation with rapid ventricular rate before initiating diltiazem drip to prevent further avoidable cardiogenic shocks. Reference #1: Fey H, Jost M, Geise AT, Bertsch T, Christ M. Kardiogener Schock nach bradykardisierender Therapie bei tachykardem Vorhofflimmern : Fallvorstellung einer 89-jährigen Patientin [Cardiogenic shock after drug therapy for atrial fibrillation with tachycardia : Case report of an 89-year-old woman]. Med Klin Intensivmed Notfmed. 2016 Jun;111(5):458-62. German. doi: 10.1007/s00063-015-0089-9. Epub 2015 Oct 6. PMID: 26440099. Reference #2: Bitar ZI, Shamsah M, Bamasood OM, Maadarani OS, Alfoudri H. Point-of-Care Ultrasound for COVID-19 Pneumonia Patients in the ICU. J Cardiovasc Imaging. 2021 Jan;29(1):60-68. doi: 10.4250/jcvi.2020.0138. PMID: 33511802;PMCID: PMC7847790. Reference #3: Murray A, Hutchison H, Popil M, Krebs W. The Use of Point-of-Care Ultrasound to Accurately Measure Cardiac Output in Flight. Air Med J. 2020 May-Jun;39(3):218-220. doi: 10.1016/j.amj.2019.12.008. Epub 2020 Jan 14. PMID: 32540116. DISCLOSURES: No relevant relationships by Fnu Aisha No relevant relationships by Lucy Checchio No relevant relationships by Ans Dastgir No relevant relationships by Shravya Ginnaram No relevant relationships by Syeda Hassan No relevant relationships by Chaitra Janga No relev nt relationships by Rameesha Mehreen No relevant relationships by Rahat Ahmed Memon No relevant relationships by Binod Poudel No relevant relationships by Shreeja Shah

CASE REPORT: USE OF THE SERAPH-100 BLOOD FILTER IN LINE WITH EXTRACORPOREAL MEMBRANE OXYGENATION CIRCUIT FOR TREATMENT OF SEPTIC SHOCK FROM ENTEROCOCCUS FAECALIS BACTEREMIA

SESSION TITLE: Close Critical Care Calls SESSION TYPE: Case Reports PRESENTED ON: 10/18/2022 11:15 am - 12:15 pm INTRODUCTION: With the development of resistant organisms, additional therapies are needed to effectively treat patients with severe infections. The Seraph®-100 Microbind Affinity Blood Filter utilizes immobilized heparinized microbeads, acting similar as the human glycocalyx, to bind and remove these substrates. In vitro and pre-clinical studies have shown up to 99% clearance of Enterococcus faecalis exposed to the Seraph®-100 blood filter. This novel extracorporeal blood purification system could assist with infection source control and reduction of vasopressor requirements. CASE PRESENTATION: A 30-year-old male with no significant past medical history was admitted due to severe ARDS secondary to COVID-19 infection and required extracorporeal membrane oxygenation (ECMO) after an unsuccessful trial of conventional supportive therapies. The patient's hospital course was complicated by multiple infections, including bacteremia from methicillin susceptible Staphylococcus aureus, candidemia and Enterobacter ventilator associated pneumonia. These infections initially improved with use of appropriate intravenous antimicrobials. However, the patient experienced an acute hemodynamic decompensation requiring multiple vasoactive medications. He was empirically started on broad spectrum anti-microbials including meropenem, vancomycin, and isavuconazole. Blood cultures revealed Enterococcus faecalis, susceptible to broad-spectrum antibiotics. After 24 hours of broad-spectrum antimicrobials without improvements in vasopressor requirements, the Seraph-100® blood filter was used in-parallel with the ECMO circuit. Immediate improvement in vasopressors was noted with discontinuation of vasopressin and decrease in norepinephrine by 75%. The patient finished a 2-week course of intravenous ampicillin/sulbactam. His respiratory status subsequently improved and he was able to be removed from ECMO 24 days later. DISCUSSION: Initial studies have shown the Seraph-100 is capable of clearing the SARS-Cov-2 virus and use has been associated with decreased mortality in patients with SARS-Cov-2. The ability to remove additional pathogens including bacteria, fungi and viruses would aid in obtaining source control and augment the effects of intravenous antibiotics. This case not only illustrates the benefits with the use of the Seraph ®-100 blood filter along with broad spectrum antibiotics, but also the ability to use this extracorporeal blood purification system in-line with ECMO. CONCLUSIONS: With the emergence of multi-drug resistant pathogens, additional treatment options are urgently needed. The Seraph®-100 may be a useful adjunct to broad spectrum antimicrobials and may improve hemodynamics in patients with vasopressor-dependent septic shock. Further prospective studies are needed to assess clinical improvements with the use of the Seraph-100 Microbind blood filter in patients with bacteremia and those requiring ECMO. Reference #1: Olson SW, Oliver JD, Collen J, et al. Treatment for Severe Coronavirus Disease 2019 With the Seraph 100 Microbind Affinity Blood Filter. Critical Care Explor. 2020;2(8):e0180. Reference #2: Chitty, Stephen, Mobbs, Sarah, Chung, Kevin et al., for the PURIFY INVESTIGATORS. A Multicenter Evaluation of Blood Purification with Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19: A Preliminary Report. medRxiv 2021.04.20.21255810;doi: https://doi.org/10.1101/2021.04.20.21255810 Reference #3: Seffer, Malin-Theres, et al. "Heparin 2.0: a new approach to the infection crisis.” Blood Purification 50.1 (2021): 28-34. DISCLOSURES: No relevant relationships by Joshua Boster No relevant relationships by Henry Danchi Speaker/Speaker's Bureau relationship with Janssen Please note: $1001 - $5000 by Michael Morris, value=Honoraria Speaker/Speaker's Bureau relationship with GSK Please note: $1001 - $5000 by Michael Morris, value=Honoraria Removed 03/29/2022 by Michael Morris No releva t relationships by Mai Nguyen No relevant relationships by Melissa Rosas No relevant relationships by Steven Stoffel No relevant relationships by Robert Walter

BETA BLOCKER AND CALCIUM CHANNEL BLOCKER OVERDOSE COMPLICATED BY COVID-19 PNEUMONIA AND RENAL FAILURE IN A PATIENT WITH SEVERE OBESITY

SESSION TITLE: A Look Into Poisoning and Drug Overdoses SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: We present a case of a 64-year-old woman with severe obesity (BMI 53) who presented with shock after beta-blocker (BB) and calcium channel-blocker (CCB) overdose. CASE PRESENTATION: The patient presented after an intentional suicide attempt, taking multiple antihypertensive medications, including tablets of nifedipine 90mg, carvedilol 25mg, and losartan 100mg. She had also been experiencing shortness of breath and lower extremity pain for several days. Upon arrival, she was lethargic and minimally responsive, and was found to be in shock with a heart rate 63. She was intubated for airway protection and started on multiple vasopressors including norepinephrine, phenylephrine, vasopressin, dopamine and epinephrine for circulatory support. She was also found to be positive for SARS-CoV-2. She was given activated charcoal, received gastric lavage, and whole bowel irrigation. She received a bolus of regular insulin at 1U/kg, and subsequently started on a high-dose insulin infusion titrated to 11U/kg/h along with dextrose infusion and calcium gluconate. By day four of admission, vasopressor requirements had been reduced to only norepinephrine and the insulin infusion had been successfully discontinued. However, her hospital course was further complicated MRSA and Pseudomonas pneumonia, and renal failure requiring hemodialysis. She continued to develop refractory shock, and remained over 50 liters net positive. Her condition progressively deteriorated and her gross volume overload was difficult to manage, and ultimately expired on day ten of admission. DISCUSSION: The management of CCB and BB overdose has been studied, with hyperinsulinemic euglycemic therapy (HIET)1,2 as our choice. Our patient's decline was likely secondary to the high volumes of dextrose infusion required after HIET. With underlying renal failure, insulin clearance proved to be a significant challenge. Such severe obesity with a weight-based regimen resulted in over 1500U insulin/hr at any given point with our patient. Renal clearance is governed by a proportion of t/V, where t denotes length of a dialysis session and V the volume of fluid in the patient's body.3 Patients with significant volume would require extensive dialysis sessions and fluid balances would be challenging. Continuous renal replacement therapy (CRRT) was attempted later in her hospital course. However, the patient was not able to tolerate it as she had progressed to multiorgan failure. CONCLUSIONS: HIET has shown to be a successful management strategy for CCB and BB overdose. However, weight-based dosing can prove to be a challenge in patients with severe obesity. CRRT should be considered early in severely obese patients that undergo HIET, given the rapid accumulation of fluid secondary to the large-volume insulin and dextrose infusions. Further investigations should look into identifying maximal safe dosages of HIET, especially in severely obese patients. Reference #1: Cole JB, Arens AM, Laes JR, Klein LR, Bangh SA, Olives TD. High dose insulin for beta-blocker and calcium channel-blocker poisoning. Am J Emerg Med. 2018 Oct;36(10):1817-1824. doi: 10.1016/j.ajem.2018.02.004 Reference #2: Krenz JR, Kaakeh Y. An Overview of Hyperinsulinemic-Euglycemic Therapy in Calcium Channel Blocker and β-blocker Overdose. Pharmacotherapy. 2018 Nov;38(11):1130-1142. doi: 10.1002/phar.2177 Reference #3: Turgut F, Abdel-Rahman E, M: Challenges Associated with Managing End-Stage Renal Disease in Extremely Morbid Obese Patients: Case Series and Literature Review. Nephron 2017;137:172-177. doi: 10.1159/000479118 DISCLOSURES: No relevant relationships by Alejandro Garcia No relevant relationships by Vishad Sheth no disclosure on file for Andre Sotelo;

A CASE SERIES OF ACUTE SYMPTOMATIC HYPONATREMIA DUE TO SIADH: AN UNUSUAL PRESENTATION OF COVID-19 INFECTION

Introduction The Syndrome of Inappropriate ADH Secretion (SIADH) is one of the most common causes of hyponatremia among medical inpatients. The evolution of SARS-CoV-2 infection over recent years has led to atypical presentations, one being in the form of acute symptomatic hyponatremia secondary to isolated SIADH not associated with pneumonia. CASES We report a series of three unusual cases of Category 2 COVID-19 infection presenting with acute symptomatic hyponatremia secondary to SIADH. All three patients presented with symptoms of acute severe hyponatremia and coincidentally tested positive for SARSCoV- 2 virus without respiratory tract symptoms and normal chest imaging. All patients were fully vaccinated and boosted at least 3 months before the presentation. Clinical and biochemical workup confirmed SIADH in all three patients. They were treated with hypertonic saline in the initial phase, followed by fluid restriction as per recommendations. It was postulated that the inappropriate ADH secretion was mediated by increased inflammatory cytokines, especially interleukin 6 may be a direct effect of the SARS-CoV-2 infection itself. Conclusion In the context of the ongoing COVID-19 pandemic, acute symptomatic hyponatremia without an obvious cause could be an atypical, isolated manifestation of SARS-CoV-2 infection. Awareness of these uncommon presentations is important so that specific treatment protocols or recommendations can be created and instituted to address this likely reversible but potentially fatal presentation of COVID-19.

Hyponatremia in brain injured patients: differential diagnosis between Cerebral Salt Wasting Syndrome and Syndrome of Inappropriate Antidiuretic Hormone secretion based on volemic state evaluation

Cerebral Salt Wasting Syndrome (CSW) is an uncommon cause of hypotonic hyponatremia associated to central nervous system disease (especially subarachnoid hemorrhage) and characterized by hypovolemia due to renal sodium loss. The main differential diagnosis is SIADH, a much more common form of hyponatremia without signs of hypovolemia. The treatment is based on filling with isotonic or hypertonic saline. We report the case of a 50-year-old chinese man with a history of arterial hypertension presenting to the ER for headache and fever after vaccination for SARS-CoV-2. In the ER he was hemodynamically stable without neurological deficits. Blood tests showed severe hypoosmolar hyponatremia. Brain CT revealed multiple hypodense oval areas of uncertain nature with peripheral contrast enhancement. The main microbiological tests were negative. In the suspicion of paraneoplastic SIADH, water restriction was prescribed and a total body CT scan was performed, resulting normal. Nevertheless, hyponatremia got worse. Brain MRI revealed signs of subacute intracranial bleeding and angiography showed an anterior cerebral artery aneurysm. An echocardiography revealed collapse of the inferior vena cava, therefore, given the hypovolemia, hypotonic hyponatremia and the signs of recent brain injury, diagnosis of CSW was made. Treatment was based on endovascular coiling of the aneurysm and correction of hypovolemic hyponatremia using isotonic saline. It is essential to differentiate between CWS and SIADH since the treatment is categorically different. Their key distinguishing feature is volemia.

Endocrine disorders in COVID-19: a look from a different perspective

Background: COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, particularly known for its respiratory symptoms. Nevertheless, a wide variety of clinical manifestations has been associated with COVID-19, including Kawasaki disease, Guillain- Barré syndrome and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Clinical Case: A 55-years-old woman, affected by immune thrombocytopenia on prednisone therapy, presented with intense fatigue, hyporexia and vomit. She had no fever, no cough, nor other symptoms. She referred a quick prednisone decalage in previous days. ABG showed metabolic alkalosis, severe hyponatremia and hypokalemia. The patient tested positive for SARS-CoV-2. Further investigation showed euvolemic hyponatremia (102 mEq/L) with normal urine osmolality (275 mOsm/Kg), findings consistent with COVID-19-related SIADH. We set a corticosteroid therapy with Prednisone 37,5 mg/die for 5 days, then 25 mg/die for 2 days. After 7 days of hospitalization, the patient tested negative for SARS-CoV-2. In the meantime, kalemia and natremia were back in range. Conclusions: Despite COVID-19 being identified as severe respiratory viral infection, progressively many relevant endocrine manifestations have been reported greatly contributing to the severity of the clinical presentation. There is the urgent need to collect in international multicentric efforts data on all these aspects of the pituitary involvement in COVID-19 patients.

Annual Conference of National Cancer Institute - Cairo University “Bridging Gaps in Oncology”

The proceedings contain 12 papers. The topics discussed include: prognostic implication of MYC/BCL2 expressions in patients with diffuse large B-cell NHL;clinical outcomes of pediatric-inspired chemotherapy protocol in adolescent and young adults (AYAs) acute lymphoblastic leukemia patients;effect of nutritional status on survival of Egyptian patients with gastrointestinal malignancies;characterization of COVID-19 disease in cancer patients, single institute experience, low income setting;malignant obstructive jaundice;review of 232 patients;determining resectability in pancreatic tumors;review of 70 cases;Inhibition of dynamins restricts the survival of vasopressin stimulated and PI3K/Akt/mTOR inhibited breast cancer cells;and complete mesocolic excision and central vascular ligation in colon cancer surgery, feasibility and outcome.

Adjusting vasopressin availability and formulation: A cost-savings initiative.

PURPOSE: The increase in vasopressin price has required many healthcare systems to consider cost-saving strategies. To combat rising medication costs, our institution changed formulations from 50 units/250 mL to 20 units/100 mL and removed vasopressin from automated dispensing cabinets (ADCs). METHODS: This retrospective review occurred at a 545-bed academic medical center with 97 adult intensive care unit beds. Adult patients receiving a continuous vasopressin infusion were included with no exclusion criteria. A 1-month period was assessed before and after changing the formulation (pre and post groups, respectively). Duplicate bags compounded by pharmacy and bedside teams were also assessed in the pre group. The primary outcome was the estimated annual cost savings due to formulation change with a secondary outcome of estimated annual cost savings due to removal of vasopressin from ADCs. Each 20-unit vial of vasopressin cost $183.21 (wholesale acquisition cost) at the time of the study. RESULTS: In the pre group, 39 patients requiring a vasopressin infusion were allocated an average of 2 bags each costing $1,099.26 per patient. In the post group, 41 patients required an average of 4 bags each costing $732.84 per patient. With respect to the primary outcome, a savings of $366.42 per patient and an average of 40 patients per month would lead to an annual cost savings of $175,881.60. Secondary outcome analysis identified 9 duplicate bags prepared in the pre group; therefore, removal of vasopressin from ADCs is estimated to provide additional cost savings of $59,360.04. The estimated annual cost savings from both initiatives is $235,241.64. CONCLUSION: Changing the vasopressin formulation and removing it from ADCs resulted in a significant cost savings to the health system.

Copeptin: a neuroendocrine biomarker of COVID-19 severity.

Aim: To investigate the change in a serum level of copeptin, a neuroendocrine biomarker, in differentiating grades of COVID-19 severity on admission time and to find its diagnostic potential. Materials & Methods: 160 COVID-19 patients were classified according to disease severity into 80 mild to moderate and 80 severe patients. Serum copeptin level was assessed by ELISA on their admission time. Besides, serum CRP, ferritin and D-dimer were estimated. Results: Severe COVID-19 patients showed higher serum copeptin level in comparison to mild to moderate cases, with diagnostic potential to distinguish disease severity with 93.33% sensitivity and 100% specificity at cutoff value >18.5 Pmol/l. Conclusion: Serum copeptin was remarkably increased with COVID-19 severity with reasonable differentiation potential for recently admitted patients.

We conducted a biochemical study on the role of copeptin ­ a biomarker of acute stress due to COVID-19 infection ­ in classification of COVID-19 severity on admission over 160 adult patients. Copeptin was highly elevated in severe cases more than the mild to moderate ones. So, it may be an early marker in admission departments to ease early clinical decisions and medical intervention.