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.

A Clinical Case of Pheochromocytoma Presenting with Decompensated Diabetes Mellitus and Paroxysmal Hypertension

Introduction: Pheochromocytoma is a rare neuroendocrine tumor that originates from the adrenal medulla, less commonly from extraadrenal chromaffin cells (paraganglioma). In about 90% of cases, the tumor produces abnormal amounts of catecholamines. Pheochromocytomas are usually benign, but in rare cases can be malignant. Typical clinical manifestations are the result of the haemodynamic and metabolic effects of catecholamines and usually include paroxysmal hypertension with the classic triad (headache, excessive sweating, palpitations), carbohydrate disorders, etc. Elevated levels of catecholamine metabolites (metanephrine and normetanephrine) tested in plasma or in 24-hour urine confirm the diagnosis. Surgical removal of the tumor is the only radical treatment. Follow-up of patients postoperatively should be lifelong and performed by a multidisciplinary team in a specialized center of expertise. Case report: A 36-year-old female patient referred to the clinic for decompensated diabetes mellitus. Detailed history revealed paroxysmal hypertension and the classic triad of pheochromocytoma. The diagnosis was confirmed by high urinary metanephrine levels and an abdominal CT scan, showing a tumor in the right adrenal gland with features typical of pheochromocytoma. Surgical removal of the pheochromocytoma and normalization of catecholamine levels led to normalization of blood pressure and reversal of diabetes mellitus. Conclusion(s): Pheochromocytoma is a difficult diagnosis in endocrinology practice as it can mimic many other diseases. Early detection and surgical removal of the tumor are crucial to avoid complications caused by elevated serum catecholamine levels.Copyright © 2022 Medical Information Center. All rights reserved.

Secondary sclerosing cholangitis in patients with COVID-19 ARDS-a specific entity associated with high mortality?

Introduction SSC-CIP (secondary sclerosing cholangitis in critically ill patients) is characterized by biliary tract destruction after long intensive care treatment. Hypotension and vasopressor therapy are main risk factors. Increased prevalence of SSC-CIP occurred in patients with COVID-19 ARDS that were treated by endoscopic retrograde cholangiography (ERC). Aims The aim of the study was to analyze clinical, laboratory, microbiological and endoscopic fndings of patients with SSC-CIP with COVID-19 ARDS. Methods Data of 17 patients with SSC-CIP with COVID-19 ARDS between February 2020 and August 2022 were analyzed retrospectively. The focus was on endoscopic fndings, laboratory and microbiological values and on clinical parameters and potential risk factors during COVID-19 ARDS. Results 14 male and 3 female patients were included. The mean age was 60 years (range 40-76). All patients were mechanically ventilated, 11 patients were treated with ECMO. All patients required catecholamine therapy but only low dosed when compared with other septic conditions. On average 2.6 ERCs were performed. Biliary casts were found in 94 % of the patients and rarefcation of the intrahepatic bile ducts in 50 %. Bile duct stenosis was detected in 3 patients. Casts were extracted and stenoses were dilated. 13 patients died, 4 patients are in follow-up with repeated endoscopic intervention and re-evaluation in regard to liver transplantation. Discussion Mortality rate in patients with SSC-CIP with COVID-19 ARDS is high. Vasopressor therapy and hypotension was not prominent in this cohort. Endo-scopic treatment may improve liver function, however these patients must be evaluated for liver transplantation.

COVID-19 and liver diseases.

In patients with coronavirus disease 2019 (COVID-19), hepatic involvement occurs in up to 53% of all cases. Via the primary target for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the angiotensin-converting enzyme 2 (ACE2) receptor, expressed on cholangiocytes, sinusoidal endothelial cells, and hepatocytes, direct damage to the liver may occur. Furthermore, indirect (= not receptor-mediated) damage to the liver plays a crucial role in the context of COVID-19 due to severe systemic inflammation with cytokine storm, hepatic thrombosis, and systemic hypoxia. In COVID-19, liver enzymes are considered significant predictors of outcome. Thus, it is essential to rule out other causes of liver enzyme elevation, such as other viral infections, drug-induced liver injury, and metabolic, autoimmune and other liver diseases. Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is highly relevant in treating critically ill patients in the intensive care unit (ICU). Risk factors for SSC-CIP include high doses of catecholamines, high positive end-expiratory pressure (PEEP), and extracorporeal membrane oxygenation (ECMO) therapy. Early recognition of this disease and treatment by endoscopic retrograde cholangiography (ERC) is crucial. Furthermore, liver transplantation should be evaluated. Some patients with COVID-19 are diagnosed with SSC, which is termed COVID-19-associated SSC. COVID-19-associated SSC and SSC-CIP are comparable with regard to clinical phenotype, risk factors, prognosis, and graft-free survival. Patients with pre-existing liver disease are not at increased risk for infection with SARS-CoV-2 but show more severe clinical courses of COVID-19 than patients without pre-existing liver disease. Patients with pre-existing liver cirrhosis may develop acute-on-chronic liver failure (ACLF) upon infection with SARS-CoV-2. ACLF has a high mortality rate, which must be treated in the ICU.Copyright © 2023, The Author(s).

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.

Advanced Nanomaterials-Based Electrochemical Biosensors for Catecholamines Detection: Challenges and Trends.

Catecholamines, including dopamine, epinephrine, and norepinephrine, are considered one of the most crucial subgroups of neurotransmitters in the central nervous system (CNS), in which they act at the brain's highest levels of mental function and play key roles in neurological disorders. Accordingly, the analysis of such catecholamines in biological samples has shown a great interest in clinical and pharmaceutical importance toward the early diagnosis of neurological diseases such as Epilepsy, Parkinson, and Alzheimer diseases. As promising routes for the real-time monitoring of catecholamine neurotransmitters, optical and electrochemical biosensors have been widely adopted and perceived as a dramatically accelerating development in the last decade. Therefore, this review aims to provide a comprehensive overview on the recent advances and main challenges in catecholamines biosensors. Particular emphasis is given to electrochemical biosensors, reviewing their sensing mechanism and the unique characteristics brought by the emergence of nanotechnology. Based on specific biosensors' performance metrics, multiple perspectives on the therapeutic use of nanomaterial for catecholamines analysis and future development trends are also summarized.

Significance of Catecholamine Biosynthetic/Metabolic Pathway in SARS-CoV-2 Infection and COVID-19 Severity.

The SARS-CoV-2 infection was previously associated with the expression of the dopamine biosynthetic enzyme L-Dopa decarboxylase (DDC). Specifically, a negative correlation was detected between DDC mRNA and SARS-CoV-2 RNA levels in in vitro infected epithelial cells and the nasopharyngeal tissue of COVID-19 patients with mild/no symptoms. However, DDC, among other genes related to both DDC expression and SARS-CoV-2-infection (ACE2, dACE2, EPO), was upregulated in these patients, possibly attributed to an orchestrated host antiviral response. Herein, by comparing DDC expression in the nasopharyngeal swab samples of severe/critical to mild COVID-19 cases, we showed a 20 mean-fold reduction, highlighting the importance of the expression of this gene as a potential marker of COVID-19 severity. Moreover, we identified an association of SARS-CoV-2 infection with the expression of key catecholamine biosynthesis/metabolism-related genes, in whole blood samples from hospitalized patients and in cultured cells. Specifically, viral infection downregulated the biosynthetic part of the dopamine pathway (reduction in DDC expression up to 7.5 mean-fold), while enhanced the catabolizing part (increase in monoamine oxidases A and B expression up to 15 and 10 mean-fold, respectively) in vivo, irrespectively of the presence of comorbidities. In accordance, dopamine levels in the sera of severe cases were reduced (up to 3.8 mean-fold). Additionally, a moderate positive correlation between DDC and MAOA mRNA levels (r = 0.527, p < 00001) in the blood was identified upon SARS-CoV-2-infection. These observations were consistent to the gene expression data from SARS-CoV-2-infected Vero E6 and A549 epithelial cells. Furthermore, L-Dopa or dopamine treatment of infected cells attenuated the virus-derived cytopathic effect by 55% and 59%, respectively. The SARS-CoV-2 mediated suppression of dopamine biosynthesis in cell culture was, at least in part, attributed to hypoxia-like conditions triggered by viral infection. These findings suggest that L-Dopa/dopamine intake may have a preventive or therapeutic value for COVID-19 patients.

A UNIQUE CASE OF SEVERE PULMONARY NOCARDIOSIS PRESENTING WITH ARDS AND CARDIOGENIC SHOCK

SESSION TITLE: Shock and Sepsis in the ICU Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Nocardiosis is a rare bacterial infection, which frequently affects immunocompromised patients. It can present as an acute, subacute, or chronic pulmonary infection with non-specific symptoms, such as fever, cough, dyspnea, weight loss, and hemoptysis. CASE PRESENTATION: A 34-year-old female with a history of chronic granulomatous disease and hidradenitis suppurativa on adalimumab presented to the ED with fever, shortness of breath, and productive cough of 2 days. Her vitals were T 101F, BP 66/48, HR 148, RR 42, and SPO2 94% on room air. On exam, she was cachectic, with bilateral crackles and rales in the right lung base. Extremities were cold, with trace pitting edema was present on bilateral lower extremities. COVID-19 PCR was negative. Despite fluid resuscitation, she remained hypotensive and was started on norepinephrine. Blood cultures were collected, and broad-spectrum antibiotics and an antifungal agent were initiated. Chest CT demonstrated bilateral multifocal consolidation with surrounding ground-glass opacities and complete consolidation of the right lower lobe. Due to worsening respiratory distress and tachypnea, and lack of improvement with non-invasive ventilation, she was intubated, placed on mechanical ventilation, and admitted to the Medical ICU. On hospital day 1, due to the patient's immunosuppression, unresolving shock, and radiographic findings, a bronchoscopy with bronchoalveolar lavage (BAL) was performed. On hospital day 2, a transthoracic echocardiogram showed LV ejection fraction of 20-25% with severe global hypokinesis of the LV. ACS workup had been unremarkable, with mildly elevated troponin and no ischemic changes on EKG. She was initiated on cardiac inotropes. On hospital day 3, BAL culture revealed Nocardia cyriacigeorgica. TMP-SMX and ceftriaxone were started for severe pulmonary nocardiosis. On hospital day 11, she was liberated from mechanical ventilation, and by hospital day 14, she was weaned off all pressors and inotropes. Approximately 4 weeks after admission, repeat TTE showed recovery of LV ejection fraction (55-60%) and she was discharged with a prolonged course of TMP-SMX and IV ceftriaxone, with duration to be determined at outpatient infectious disease follow-up. DISCUSSION: We discuss a unique case of severe pulmonary nocardiosis, presenting with ARDS and cardiogenic shock. To the best of our knowledge, this is the first case of a patient with pulmonary nocardiosis presenting with stress cardiomyopathy reported in the literature. While the pathophysiology is not well understood, theorized mechanisms include catecholamine excess, coronary artery spasm, microvascular dysfunction. CONCLUSIONS: This case highlights the need for a broad differential diagnosis in patients presenting with ARDS and cardiogenic shock and illustrates the value of clinical bronchoscopy in patients with unique presenting features. Reference #1: Lerner PI. Nocardiosis. Clin Infect Dis. 1996 Jun;22(6):891-903;quiz 904-5. doi: 10.1093/clinids/22.6.891. PMID: 8783685. Reference #2: Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med. 2005 Feb 10;352(6):539-48. doi: 10.1056/NEJMoa043046. PMID: 15703419. Reference #3: Park JH, Kang SJ, Song JK, Kim HK, Lim CM, Kang DH, Koh Y. Left ventricular apical ballooning due to severe physical stress in patients admitted to the medical ICU. Chest. 2005 Jul;128(1):296-302. doi: 10.1378/chest.128.1.296. PMID: 16002949. DISCLOSURES: no disclosure on file for D. Clark Files;No relevant relationships by Nisha Patel No relevant relationships by Meehir Shah

Just a flue with heart failure

In January 2022 we treated two young patients (26y & 37y) that were admitted to hospital because of fever and flu-like symptoms (Respiratory symptoms resp. abdominal symptoms). Due to a septic condition with significantly elevated inflammatory blood values (CRP 389mg/L, resp. 270mg/L) and pneumonic infiltrate, they were hospitalised and an antibiotic therapy was initiated. Shortly after admission, they became increasingly hemodynamic instable and were transferred to the intensive care unit with a catecholamine and oxygen dependency, severely decreased ejection fraction (20% resp. 40%), pericardial and pleural effusions and highly elevated cardiac markers (Trop-T: 2406ng/L, resp. 1874ng/L / NT-proBNP: 17805pg/mL, resp. 14976pg/mL). All blood cultures, Ag-tests, immune serologies were negative, but the patients were suffering from a cardiogenic shock with SIRS. Only a COVID-infection (mild symptoms resp. asymptomatic, PCR tested in 12/2021) three to four weeks past was remarkable in their health history. They received one resp. no vaccination before infection. Therefore the heart failure was interpreted as a myocarditis and the symptom complex as Multisystem Inflammatory Syndrome in Adults (MIS-A). The following days, they were treated with high-dose steroids (500mg resp. 250mg) at first, to which they responded well combined with catecholamines and inotrops. After a continued improving heart and infection blood work a slowly tapering regimen of the steroid therapy (down to 1mg/kg KG) and an IVIG therapy (2g/kg KG) for five days was initiated. The echocardiographic monitoring showed a positive development with a regression of the pericardial effusion and a normal cardiac output. With an improving general condition, the patients were discharged to either cardiac rehabilitation or home. A cardio MRT showed typical findings of a peri-/myocarditis with epicardial late-gadolinum enhancement (LGE) and in one patient additionally with myocardial LGE and edema. The intention of this case series is to report on the rare but potentially lethal MIS-A, especially in a younger age group, predominant male after COVID-infection. Prompt recognition of MIS-A with immunomodulatory treatment is necessary to limit the hyperinflammatory response. In the reported cases, it was especially remarkable that the patients underwent a mild initial infection and after a latency of several weeks a rapidly progressive reaction of immune disorder occurred.

NIGHT SWEATS IN AN ELDERLY FEMALE

CASE: 74 year old woman with history of anxiety, depression, and nonsecretory adrenal adenoma presented with two months of progressive night sweats. Initially, she described waking up damp all over, but without needing to change her sheets. Her weight had been stable, and she denied recent travel. Her recent health changes included starting sertraline and receiving the Moderna COVID vaccines. Her other medications included atorvastatin and lisinopril. Her vital signs were all within normal range and her physical exam was unremarkable. Night sweats described were mild, so work up began with checking a CBC with differential and a TSH level. Initial labs were normal. However, the patient called a week later with night sweats that were worsening. She also recalled being treated for tuberculosis at age fifteen. This prompted additional bloodwork including Quantiferon, ACTH, androstenedione, estradiol, testosterone, progesterone, and DHEAS levels, as well as urine catecholamines and metanephrines. Additionally, it was noted sertraline could be a potential cause of night sweats. The dose was halved with the goal to taper off and discontinue the medication. All lab results came back within normal limits, so CT scans of the chest/ abdomen/ pelvis were ordered, and blood cultures collected. Imaging showed an unchanged adrenal adenoma and blood cultures had no growth. Ultimately, after five months of symptoms, her night sweats completely resolved five weeks after stopping sertraline. IMPACT/DISCUSSION: When working up night sweats, first, the severity of symptoms should be determined and medications reviewed. Mild night sweats with no associated red flag symptoms (weight loss, lymphadenopathy, and fever) do not need immediate or extensive work up. Further work up is essential in the setting of any red flag symptoms. Without a clear etiology, the work up includes the following items: chest radiography along with bloodwork including Quantiferon test, CBC, TSH, HIV serology, and CRP. If these results are normal then a CT of the chest, abdomen, and pelvis could be obtained as well as a bone marrow biopsy. Little evidence exists to guide an exact order of workup for night sweats, so it remains the clinician's responsibility to determine which tests to prioritize. Classes of medications that tend to cause night sweats are cholinergics and anti-depressants. Anti-depressants most associated with night sweats include TCAs and SNRIs. Sertraline has been implicated as a cause of night sweats, but little data exists as to how often this occurs and how often severe presentations like the one described occur. Given that selective serotonin reuptake inhibitors are a first line treatment in depression, recognizing this adverse effect is important in primary care and could prevent unnecessary extensive work ups for night sweats. CONCLUSION: -An initial step in evaluating persistent night sweats should be medication review -Many antidepressants including sertraline can have night sweats as an adverse effect.

Immunological characterization of COVID-19 endotypes of critically ill patients

Introduction Over the last 20 months Sars-CoV-2 research revealed tremendous insights into the pathophysiology resulting in vaccines and first immunomodulatory therapies in an unprecedented short time [1]. However, the patient's individual clinical course is remarkably heterogenous and the effectivity of immunomo-dulatory therapies especially in critically ill patients is still very variable [2]. Therefore,a better understanding of the patients' individual immune response is needed [3]. Methods Unbiased machine learning grouped 323 Covid-19 patients treated at the Klinikum Rechts der Isar ICU into 3 different clusters. For this we queried the ICU electronic files and analyzed relevant clinical features (Fig. 1+2). To delineate biological differences within these clusters, we applied a 14 parameter flow cytometric panel to PBMCs from 27 of these CoV2 ICU patients. Flow data was analyzed using FlowJo and the FlowSOM package for unsupervised clustering (Fig. 3+4). Written informed consent was obtained from all patients and healthy controls. The study was approved by the local ethical review board (Az249/20 S-EB). Results Patients from cluster 1 had above ICU average respiratory function (Fig. 2), reduced liver function and received lower dose catecholamines. Immunologically these patients had significantly higher amount of CD3+CD4+ T helper cells (Fig. 5). Whilst B cell numbers were reduced, they were highly activated (HLA-DR-ordf). Activated monocytes produced high amounts of TNFa. Interestingly, proinflammatory CD14+ HLA-DRlow monocytes were not increased. Cluster 2 contains patients with renal impairment, an increased tendency for bacterial infection and elevated blood lactate levels. Cluster 3 is made up of long-term ICU patients with severely reduced respiratory function and high ECMO-dependency (Fig. 1). These patients had significantly increased ratios of activated innate immune cells. We have detected elevated levels of an interesting population of CD14+ HLA-DRlow monocytes, a well-established player of immune suppression [4], while cytotoxic T cells and B cells were found to be significantly reduced. Conclusion These data provided evidence that clinically defined endotypes of critically ill Covid-19 patients exhibit a distinct immune profile. The immunological differences support our theory that these endotypes might require personalized immunomodulatory therapies to restore the pro-regenerative cell function in ICU Covid-19 populations and improve patient outcome in the future.

COVID-19 ASSOCIATED REDUCTION IN HYPERTENSION-RELATED DIAGNOSTIC AND THERAPEUTIC PROCEDURES IN EXCELLENCE CENTERS OF THE EUROPEAN SOCIETY OF HYPERTENSION

Objective: The Covid-19 pandemic necessitated a decrease in non-Covid-19 related diagnostic and therapeutic procedures in many countries. We explored the impact on hypertension care in the Excellence Center (EC) network of the European Society of Hypertension. Design and method: We conducted an electronic survey regarding 6 key procedures in hypertension care among our ECs. Results: Overall, 54 ECs from 18 European and 3 non-European countries participated. From 2019 to 2020, there was a significant decrease in the median number per center of ambulatory blood pressure monitorings (ABPMs;544 vs 289), duplex ultrasound investigations of renal arteries (DUS RA;88.5 vs 55), computed tomographic investigations of renal arteries (CT RA;66 vs 19.5), percutaneous renal artery angioplasties (PTA RA;5 vs 1), laboratory tests for catecholamines (2019: 116 vs 67.5) and for ennin/aldosterone (146 vs 83.5). All comparisons were statistically significant with p < 0.001, respectively (Figure). While the reduction in all diagnostic and therapeutic procedures was observed in all 3-months period comparisons between 2019 and 2020, the most profound decrease occurred from April to June 2020, which was the period of the first wave and the first lockdown in most countries. In this period, as compared to 2019, the median reduction in 2020 was 50.7% (ABPM), 47.1% (DUS RA), 50% (CT RA), 57.1% (PTA RA), 46.9% (catecholamines) and 41% ( ennin/aldosterone), respectively. Based on Friedman test, overall differences in reduction between 3 months time intervals were statistically highly significant. Conclusions: Diagnostic and therapeutic procedures related to hypertension were dramatically reduced during the first year of the Covid-19 pandemic, with the largest reduction during the first lockdown. The long-term consequences regarding blood pressure control and, ultimately, cardiovascular events remain to be investigated.

Defer Thy Diuresis

With the spread of the novel coronavirus disease 2019 (COVID-19) pandemic, an alarming number of patients now present with acute respiratory distress syndrome (ARDS). Conservative fluid management with diuresis in the ARDS patients improves lung function and decreases ventilator-dependent days. Several cardiac manifestations have been reported in COVID-19 patients including rhythm disorders, myocarditis, Takotsubo cardiomyopathy and myocardial infarction. A 65-year-old Asian female with a history of hypertension presented to the emergency department with cough, worsening dyspnea and palpitations of one-week duration. Investigations at admission were significant for a positive COVID-19 polymerase chain reaction test with an electrocardiogram (EKG) (Figure 1 Panel-A) revealing inferior ST-elevations. Troponin-T was elevated to 1162 ng/L with bedside echocardiogram revealing inferior hypokinesis. Due to concerns for acute ST-elevation myocardial infarction (STEMI), the patient underwent cardiac catheterization with no obvious coronary artery occlusion. A ventriculogram revealed apical ballooning and the patient was treated for COVID-19 induced Takotsubo cardiomyopathy. The patient developed worsening respiratory distress on hospitalization day 3 requiring oxygen supplementation with a high-flow nasal cannula. Conservative fluid regimen and diuretic therapy were being administered when the patient developed ventricular fibrillation and suffered a cardiac arrest. After successful resuscitation, a repeat EKG (Figure 1 Panel-B) demonstrated new anterior and inferior ST-elevations. The patient required increasing vasopressor support, and a repeat cardiac catheterization to rule out coronary artery thromboembolism induced STEMI was negative. A right heart catheterization revealed elevated SVR with decreased cardiac index. The patient clinically deteriorated despite negative fluid balance with recurrent malignant arrhythmias. A bedside echocardiogram performed revealed persistent apical hypokinesis and systolic anterior motion of anterior mitral leaflet (Figure 1 Panel-C) with flow acceleration at left ventricular outflow tract (LVOT) (Figure 1 Panel-D). Due to concerns of cardiogenic shock secondary to Takotsubo cardiomyopathy with dynamic LVOT obstruction physiology, the patient was treated with liberal intravenous fluid resuscitation and successfully weaned from vasopressor therapy. Although she was successfully extubated 2 days later, the patient, unfortunately, passed away later from a thromboembolic stroke. Severe COVID-19 infections are associated with catecholamine surge which may precipitate Takotsubo cardiomyopathy in the susceptible patient population. Female patients with Takotsubo cardiomyopathy are at increased risk of developing dynamic LVOT obstruction. In these patients, management of shock and ARDS can be challenging as the use of inotropic agents may result in hemodynamic instability. Our patient was successfully hemodynamically stabilized using fluid resuscitation once the inotropic support was withdrawn after identifying dynamic LVOT obstruction.

Multisystem Inflammatory Syndrome in Children (MIS-C)- A Case Report with severe Cardiac Involvement

We present the case and course of a 10-year-old girl with a multisystem inflammatory syndrome in children (MIS-C) following SARS CoV-2 infec-tion. The previously healthy girl was referred to our emergency department due to persistent fever, reduced general condition, thrombocytopenia and elevated CRP. Clinical exanimation confirmed a reduced condition and revealed bilateral conjunctivitis, palmar, facial and thoracal ery-thema, sinus tachycardia and fever. Diagnostics, including a negative SARS-CoV-2 test, showed pancytopenia, elevated liver enzymes and CRP. Initial echocardiography and ECG were normal. Based on history, clinical presentation and laboratory results reflecting a multisystem affection we considered sepsis, Kawasaki disease and as a result oft the SARS-CoV-2 pandemic MIS-C despite negative test. Treatment included antibiotics, in-travenous immunoglobulins (IVIG) and systemic corticosteroids. The condition worsened on the third day of hospitalization with clinical signs of heart failure due to new-onset myocarditis. Echocardiography showed a reduced biventricular function. There were repolarization ab-normalities in ECG and elevated cardiac enzymes. The patient was then referred to ICU of a tertiary hospital for further treatment. Meanwhile SARS-CoV-2 infection was proven via positive antibodies. The girl was sta-bilized with high-flow therapy, catecholamines, diuretics, low-dose ace-tylsalicyl acid (ASA) and high-dose corticosteroids. Due to persistent fever, antibiotic therapy was extended and immune-modulating medication (Anakinra) was prescribed. Within a few days, cardiac function improved, cardiac enzymes normalized and there were no signs of coronary dilation. After 6 days and a second course of IVIG, the patient was transferred from ICU to the hospital ward. The patient was discharged in good general condition after 13 days of hos-pitalization with low dose ASA for 8 weeks and Prednisolon for 2 weeks in total. Regular outpatient controls showed normalized cardiac function. After 6 months, a cardiac MRI was performed showing no signs of myocardial damage and normal coronary arteries. The patient was suffering from breathlessness and general weakness for several months. Six months af-ter primary diagnosis of MIS-C she was allowed to participate in normal physical exercise again. Summarized, pediatricians need to be aware of MIS-C as a serious condi-tion whenever children present with persistent fever, rash and clinical signs of multiorgan affection.

Dysglycemia in ICU Patients

Dysglycemia has emerged as a very common challenge in critically ill patients, especially with regard to current coronavirus disease 2019 pandemic. Prediabetes, poorly controlled diabetes, pharmaceutical intervention in intensive care unit (ICU) with glucocorticoids, catecholamines and other medicines, and stress response all contribute to dysglycemia in critically ill patients. Early identification and management are the key to prevent further complications. Patient prognosis in terms of clinical outcome, length of ICU stay, and in-hospital morbidity/mortality are adversely affected by patient's dysglycemic status. Apart from hyperglycemia, the other three important pillars of dysglycemia are discussed in this article. Synopsis of early intervention have been captured from India-specific practice guidelines. Important landmark trials have also been captured in this article to provide a clarity on certain aspects of managing dysglycemia in ICUs. Hence, this review article is an attempt to bring forth the salient aspects in diagnosing and managing dysglycemia in critical care settings.

Cardiac Arrest in COVID-19 Patient Presenting with Takotsubo Cardiomyopathy

Background: Takotsubo cardiomyopathy (TC) presents as a result of catecholamine surge. There are increase of TC among COVID-19 patients, which is induced by cytokine storm. TC is previously known as a self-limiting and benign cardiac manifestation, but it has been uncovered that TC can be associated with fatal cardiac outcome due to cardiogenic shock and life-threatening arrhythmia. Clinical Presentation: A 54-year-old woman presented to the emergency department with a fever since 9 days before admission accompanied by DOE, PND, and fatigue that worsened since 5 days before admission. Fifteen days before her complaints, she experience bereavement from his son death from motorcycle accident. She was referred from regional hospitals due to respiratory failure necessitating ventilator support. Physical examination revealed normal blood pressure and desaturation. ECG shows tachycardia with global ST-elevation. CXR shows cardiomegaly (CTR 62%) and pneumonia. The laboratory demonstrated increased Neutrophil to Lymphocyte Ratio (NLR), C-Reactive Protein, Troponin, and positive PCR COVID-19 swab. An echocardiography presented regional wall motion abnormality with apical ballooning appearance and reduced systolic function with LVEF of 51% resembling Takutsubo cardiomyopathy. Despite maximal ventilatory and pharmacology, she experienced malignant ventricular tachycardia not responding to defibrillation and expired in only 6 hours Discussion: The presence of cardiac arrhythmia followed by cardiac arrest in COVID-19 patient complicated by TC can be a direct effect of catecholamine surge and myocardial injury or indirect effect from QT-prolongation and inflammatory process. Concurrent COVID-19 pneumonia and TC may progress with dismal prognosis, so that in need of prompt referral system.

Successful Management of Pheochromocytoma Crisis with Cardiogenic Shock by Percutaneous Left Ventricular Assist Device.

Therapeutic strategy utilizing mechanical circulatory supports in patients with pheochromocytoma-related cardiogenic shock remains unestablished. We had a 51-year-old man with acute decompensated heart failure due to pheochromocytoma crisis. He received a percutaneous left ventricular assist device-supported alpha-blocker and intensive fluid infusion therapy, which ameliorated impaired end-organ dysfunction, maintaining hemodynamics and achieving cardiac recovery, followed by the successfully scheduled adrenalectomy. Early suspicion of pheochromocytoma and Impella-supported disease-specific medical management might be a promising bridge to surgery strategy.

Takotsubo cardiomyopathy due to hemophagocytic lymphohistocytosis secondary to COVID-19 pneumonia

Case Report Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal disease characterized by excessive immune response and cytopenia. Severe COVID-19 infection induces a life-threatening inflammatory syndrome associated with intense cytokine release that similar to HLH. We present a patient who developed takotsubo cardiomyopathy due to HLH. Case 24-year olrd man with a past medical history of obesity was admitted at the medical intensive care unit (MICU) due to acute respiratory distress syndrome secondary to COVID- 19 pneumonia. During the MICU stay, the patient required a high dose of vasopressors and ventilatory support. For Covid management, the patient received tocilizumab, high dose steroids (20 mg daily of dexamethasone), and empiric antibiotic coverage with vancomycin and cefepime. On day six of MICU admission, the patient developed hypertriglyceridemia (TGL) that was initially thought to be secondary to propofol, but after discontinuing propofol the patient continued to have increasing TGL levels. On day 8 of MICU admission, the suspicion of HLH increased, HSscore was calculated, and the patient had a 70-80% probability of having HLH (181 points: Temperature of 103 °F, ferritin 2580 ng/ml, TGL:771 mg/dl, Fibrinogen 220 mg/dl, AST:116 u/L). On day 10 of MICU admission, troponins increased from 7.5 to 2,966 ng/L, telemetry showed diffuse ST elevations, but ECG did not show any ischemic changes. At that time, his clinical parameters included HR: 96 bpm, BP: 92/42 mmHg, O2 Sat:93% on mechanical ventilation with pressure support FIO2: 100%, Hb: 11.6 g/dl, WBC:10.36 k/dl, Plt: 210 k/dl. Acute stress cardiomyopathy secondary to HLH was suspected. Transthoracic echocardiogram demonstrated preserved ejection fraction and inferoapical akinesia consistan as takotsubo cardiomyopathy. On day 11 of MICU admission, the patient had a cardiac arrest and after 30 minutes of cardiopulmonary resuscitation no return of spontaneous circulation was achieved. Discussion HLH induces a cytokine cascade that causes an excessive inflammatory response and multi-organ dysfunction that can be secondary to infections such as Covid-19. Takotsubo cardiomyopathy also known as stress cardiomyopathy, is a reversible dysfunction characterized by acute hypokinesia/ akinesia of the apical and middle segments of the left ventricle that extends beyond a unique coronary territory. We conclude that the trigger for takotsubo cardiomyopathy in this case was related to excess catecholamine release secondary to HLH.

Complications and specific considerations in managing newly diagnosed DKA with COVID-19;Challenges in managing DKA with COVID-19 infection

Introduction: New cases of type 1 diabetes (T1D) remain commonly found in Indonesia. One of the most typical presenting symptoms is diabetic ketoacidosis (DKA);approximately 71% of all cases. There has been several reports of the negative association between type 2 diabetes (T2D) and Coronavirus disease (COVID-19) cases in adults, but T1D and COVID-19 cases in children are still scantily studied. Mortality of COVID-19 pediatric case could reach higher than 50% in children below 5 years old. Objectives: Early detection and prompt treatment for DKA, T1D and COVID-19 should be emphasized. Methods: This case described new-onset T1D presented with DKA and severe COVID-19 infection. Results: 7-year-old boy was presented with altered consciousness, epigastric pain, dehydration, dyspnea, history of nocturnal enuresis, polydipsia, and polyphagia. Random blood glucose (BG) was 516 mg/dL, blood ketone 5.2 mmol/L, A1c 15%, pH 6.932, pCO2 16 mmHg, pO2 153.8 mmHg, base excess-26.5 mmol/L, HCO3 3.4 mmol/L, and positive polymerase chain reaction COVID-19 with E gene Cq of 30.66. The patient was treated in isolation PICU as severe DKA with hypovolemic shock and confirmed COVID-19 case;received fluid resuscitation, intravenous insulin with saline and dextrose infusion and remdesivir. The patient had recurring hyponatremia, hyperkalemia, hypophosphatemia, increased coagulation markers, and had catecholamine-resistant shock, and received hydrocortisone from 2 mg/kg/day and subsequently titrated. The patient regained consciousness on the 2nd day of admission, and were stable on the 5th day of admission. The patient's condition improved on day 6 of admission and insulin and hydrocortisone were weaned. COVID-19 PCR test yielded negative result on day 9 of admission. Conclusions: The COVID-19 pandemic presents additional unwanted complications in both clinical and non-clinical aspects of DKA and T1D management. Special considerations should be highlighted considering the comorbidities and medications given in addition to the treatment for DKA.

A case report of fearsome infection from CoViD-19 that after the lungs also affected the heart!

Background: Takotsubo cardiomyopathy (TC) is an acute and reversible form of heart failure, originating from acute stress and probably due to increase in circulating catecholamines, presenting with a transient balloon-like modification of the left ventricular apex, resembling as the octopus basket used by Japanese fishermen, visible with echocardiography or cardiac RMI. Description of the case: A 61-aged female hypertensive patient with CoViD-19 infection for two weeks was admitted to our Department for sudden chest pain, precordial discomfort, cardiopalmus onset in the previous hours. Cardiac clinical evaluation: normal. All vital parameters: normal except body T 37°C, O2 Sa 96%. ECG-1: V1-V2 slight ST and T-waves changes. Laboratory data: slight leucocytosis, rise of CRP, D-dimer, positive IgM-Ab anti- CoViD-19 test;negative myocardial enzymes. Chest-X-ray: interstitial bilateral pneumonia. Echocardiogram: Akinesia/hyperkinesis of the LV. Coronary-angiography: non-obstructive coronary arteries but apical ballooning on ventriculography consistent with TC. Treated on methylprednisolone, tocilizumab and NIV, she improved within 2 weeks with normalization of all laboratory findings and she was discharged in healthy. Conclusions: SARS-CoV-2 has resulted in a viral pandemic with high mortality rate and possible involvement of myocardium since the patients can experience acute myocarditis, pericarditis, TC and acute myocardial infarction. Given all this, we should probably expect an increase in cases of myocardial diseases in the coming years as a complication of the CoViD-19 viral insult!.