Cardiac troponins: Mechanisms of release and role in healthy and diseased subjects.

The cardiac troponins (cTns), cardiac troponin C (cTnC), cTnT, and cTnI are key elements of myocardial apparatus, fixed as protein complex on the thin filament of sarcomere and are involved in the regulation of excitation-contraction coupling of cardiomyocytes in the presence of Ca2+ . Circulating cTnT and cTnI (cTns) increase following cardiac tissue necrosis, and they are consolidated biomarkers of acute myocardial infarction (AMI). However, the use of high sensitivity (hs)-immunoassay tests for cTnT and cTnI has made it possible to identify a multitude of other clinical conditions associated with increased circulating levels of cTns. cTns can be measured also in the peripheral circulation of healthy subjects or athletes, suggesting that different mechanisms are involved in the release of cTns in the blood independently of cardiac cell necrosis. In this review, the molecular/cellular mechanisms involved in cTns release in blood and the exploitation of cTnI and cTnT as biomarkers of cardiac adverse events, in addition to cardiac necrosis, are discussed.

Potential of Hesperidin in the Medicinal Field

Hesperidin has gained major interest recently due to the outbreak of COVID-19. The traction has led to more research being conducted on the compound hesperidin. Recent studies have shown its anti-inflammatory and anti-viral attributes, which have beneficial effects on severe acute respiratory syndrome (SARS-CoV-2). Hesperidin has also shown unique effects on the protein of SARS-CoV-2, which lead to a good preventative measure for SARS-CoV-2. Hesperidin also causes a suppression of appetite, which helps to combat obesity through the release of cholecystokinin. Furthermore, hesperidin has shown cardioprotective properties, which cause an increase in plasma high-density lipoprotein levels and a decrease in plasma low-density lipoprotein levels. Hesperidin is also used in combination with the Japanese herb Rikkunshito, which has shown potential in a discovery of a new drug for gastrointestinal motility as hesperidin can depolarize pacemaker potential in interstitial cells of Cajal (ICC). The chemo-preventive effects of hesperidin are caused by its antioxidant effect, which may prevent tissue necrosis due to oxidative stress. The photo-protective effect of hesperidin can reduce the damage to the skin caused by UV rays. Hesperidin also possesses wound-healing properties.Copyright © 2023 Bentham Science Publishers.

Post-Coronavirus Disease Mucormycosis: Predisposing Factors and Possible Treatment: A Narrative Review

Mucormycosis, commonly known as black fungus, is a life-threatening fungal infection be-longing to the order Mucorales. It affects individuals with an impaired immune response or immune disorders such as diabetes mellitus, induced immunosuppression, hematological cancers, acquired immune deficiency syndrome, or who have undergone organ transplantation. The symptoms of black fungus in-clude difficulty in breathing, blurred vision, coughing out blood, chest pain, and blackening over the area of the nose. Tissue necrosis is the main symptom of this infection. Its prevalence is increasing day by day and has been observed in vulnerable patients, including patients suffering from COVID-19 (corona-virus) and those who have been recovered. It has been observed that black fungus cases are increasing in recovered COVID patients, and various cases of white and yellow fungus are also reported. The treatment approach includes the use of antifungal agents, triazoles, surgery, combination therapy, etc. This review describes the clinical manifestation, predisposing factors, and treatment strategies of mucormycosis.Copyright © 2022 Bentham Science Publishers.

Isolated tracheobronchial mucormycosis: Report of a case and systematic review of literature

Background: Isolated tracheobronchial mucormycosis (ITBM) is an uncommonly reported entity. Herein, we report a case of ITBM following coronavirus disease 2019 (COVID-19) and perform a systematic review of the literature. Case description and systematic review: A 45-year-old gentleman with poorly controlled diabetes mellitus presented with cough, streaky haemoptysis, and hoarseness of voice 2 weeks after mild COVID-19 illness. Computed tomography and flexible bronchoscopy suggested the presence of a tracheal mass, which was spontaneously expectorated. Histopathological examination of the mass confirmed invasive ITBM. The patient had complete clinical and radiological resolution with glycaemic control, posaconazole, and inhaled amphotericin B (8 weeks). Our systematic review of the literature identified 25 additional cases of isolated airway invasive mucormycosis. The median age of the 26 subjects (58.3% men) was 46 years. Diabetes mellitus (79.2%) was the most common risk factor. Uncommon conditions such as anastomosis site mucormycosis (in two lung transplant recipients), post-viral illness (post-COVID-19 [n = 3], and influenza [n = 1]), and post-intubation mucormycosis (n = 1) were noted in a few. Three patients died before treatment initiation. Systemic antifungals were used in most patients (commonly amphotericin B). Inhalation (5/26;19.2%) or bronchoscopic instillation (1/26;3.8%) of amphotericin B and surgery (6/26;23.1%) were performed in some patients. The case-fatality rate was 50%, primarily attributed to massive haemoptysis. Conclusion: Isolated tracheobronchial mucormycosis is a rare disease. Bronchoscopy helps in early diagnosis. Management with antifungals and control of risk factors is required since surgery may not be feasible. © 2022 Wiley-VCH GmbH.

Preliminary Experience in Post-COVID-19 Mycoses: A Pathologist's Perspective.

Background Coronavirus disease is caused by the severe acute respiratory syndrome coronavirus-19. Because of co-morbidities and indiscriminate use of steroids and antibiotics, the incidence of opportunistic fungal infections has increased in COVID-affected individuals. Aims and objectives The aim of the study is to analyze the various tissue reaction patterns of COVID-19-associated mucormycosis in the surgical debridement specimens using routine hematoxylin and eosin (H&E) stain and special stains like periodic acid-Schiff (PAS), Grocott-Gomori's methenamine silver (GMS), Masson trichrome (MT) and Prussian blue (PB), and to understand the pathogenesis of COVID-19 sequelae. Materials and methods This retrospective observational study was conducted after the approval from the Institute Human Ethical Committee (IHEC) on 45 tissue samples of COVID-associated mucormycosis using routine H&E and histochemical stains such as PAS, GMS, MT, and PB. Detailed demographic profiles, clinical information, radiological findings, and relevant microbiological data in available cases, like reports on potassium hydroxide (KOH) mount preparation, and fungal culture reports on Saboraud's Dextrose Agar (SDA) medium were collected. The different histomorphological tissue reaction patterns were observed and analyzed. Results All the surgical debridement specimens from post-COVID cases had histomorphology of mucormycosis displaying broad, aseptate, ribbon-like fungal hyphae with right-angle branching (45/45). Six of the 45 cases also reveal thin, narrow septate, acute angle branching hyphae, indicating co-existing Aspergillosis (6/45). The histological tissue reaction patterns observed were categorized as extensive tissue necrosis (100%), vascular proliferation (82%), angioinvasion (58%), giant cell reaction (53%), fibrin thrombi (47%), septic thrombi and angiodestruction (40%), fungal osteomyelitis (33%), necrotizing granulomas (31%). Conclusion This study infers that post-COVID-19 associated mucormycosis, alterations in the local tissue microenvironment are found to have a favorable effect on colonizing fungi and result in destructive tissue reactions such as angioinvasion, angiodestruction, necrosis, necrotizing granulomas, suppurative inflammation, and iron pigment deposition. The spectrum of morphological changes reflects the host's immune status.

RARE CASE OF A NONTRAUMATIC LEFT MAIN BRONCHIAL TEAR

SESSION TITLE: Bad bugs and Mediastinal Madness SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: Non-traumatic bronchial injury (NTBI) incidence is not well described but traumatic Tracheobronchial injury (TBI) incidence is 3% with a 70 -100% mortality3. Causes identified for NTBI are associated with vascular supply compromise2. TBI presents with dyspnea, subcutaneous emphysema, pneumothorax, and/or pneumomediastinum4. It can be missed up to 68% of the cases. Bronchoscopy is the study of choice and management is based on studies from traumatic TBI2, 3. This report describes a unique case of NTBI in a patient with recent COVID-19 infection, uncontrolled diabetes, and invasive pseudomembranous Aspergillosis presenting with a left bronchial tear (LBT). CASE PRESENTATION: A 41-year-old with uncontrolled diabetes and prior admission for COVID-19 infection and diabetic ketoacidosis (DKA) managed with steroids and antibiotics. Presenting cough, fever, intermittent chest pain, and palpitations. He was afebrile, tachycardic, and hypoxemic requiring supplemental oxygen. Chest examination revealed crackles and decreased breath sounds at the lung bases. Laboratory studies showed leukocytosis, hyperglycemia, and anion gap metabolic acidosis. SARS-CoV-2 PCR was negative. CT chest revealed an anterior wall defect of the left bronchus with a pneumomediastinum. Bronchoscopy showed pseudomembranous necrotic debris of the tracheobronchial tree and left main bronchus tear with visible rhythm-beating pericardium surrounding the heart. Cytopathological findings of the bronchoalveolar fluid were consistent with Aspergillus species (AS). DISCUSSION: NTBI are rare with a high mortality3. NTBI due to AS has been described in post-lung transplant patients. AS produces endotoxins and proteases that damage the epithelium, leading to erosion of surrounding structures2,3. Since COVID-19, invasive fungal infections (IFI) have risen due to lung damage and immunologic deficits associated with the virus or immunomodulatory therapy6. Our patient risk factors for IFI included recent COVID-19 infection, steroid use, and uncontrolled diabetes. This unholy trinity has coexisted during COVID-19 self-potentiating the problem of immune dysregulation leading to IFI and tissue necrosis7. This may cause NTBI as in our case presenting with LBT. Despite antimicrobial therapy, he died due to massive hemoptysis from erosion of the pericardium or angio-invasion of surrounding vessels. CONCLUSIONS: Rarity of NTBI constitutes a challenge for early diagnosis and management. Identifying predisposing risk factors, a high clinical suspicion, and appropriate diagnostic workup is of vital importance. During the COVID-19 pandemic, IFI have an increased incidence associated with high mortality rates. Despite more cases being described there are still knowledge gaps related to prevention, diagnosis, and management. Reference #1: Jones D, Nelson A, Ma OJ. Pulmonary Trauma. In: Tintinalli JE, Stapczynski JS, Ma OJ, Yealy DM, Meckler GD, Cline DM, eds. Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 8e. McGraw-Hill Education;2016. accessmedicine.mhmedical.com/content.aspx?aid=1121516674 Reference #2: Aerni MR, Parambil JG, Allen MS, Utz JP. Nontraumatic Disruption of the Fibrocartilaginous Trachea: Causes and Clinical Outcomes. Chest. 2006;130(4):1143-1149. doi:https://doi.org/10.1016/S0012-3692(15)51151-3 Reference #3: AK AK, Anjum F. Tracheobronchial Tear. StatPearls Publishing;2022. Accessed March 13, 2022. https://www.ncbi.nlm.nih.gov/books/NBK560900/ DISCLOSURES: No relevant relationships by Jorge Alejandro Bernal No relevant relationships by Adriana Betancourth No relevant relationships by Reham Majzoub No relevant relationships by Juan Pablo Sarmiento Cano

COVID-19-ASSOCIATED PULMONARY MUCORMYCOSIS PRESENTING AS SPONTANEOUS PNEUMOTHORAX: A RARE PRESENTATION

SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Mucormycosis is an angio-invasive fungal infection with substantial morbidity and mortality. While diabetes and immune suppression remain well-known risk factors for mucormycosis, COVID-19 is now emerging as its independent predictor. CASE PRESENTATION: A 43-year-old male, with a history of hyperlipidemia and alcoholism, presented to the hospital with complaints of progressive dyspnea on exertion, productive cough, intermittent fever, anorexia, and chest pain over the course of 2 weeks. About 5 weeks prior to the current presentation, he was tested positive for COVID-19 by a polymerase chain reaction (PCR) based test and remained in quarantine at home. He was not vaccinated against COVID-19. He had no known immunosuppressive disease. On initial examination, he was ill-appearing and had a temperature of 101 F, blood pressure 138/83 mmHg, respiratory rate 22/minute, pulse 102/minute, and saturation of 91% on 2 L nasal cannula oxygen. A computerized tomography (CT) scan of the chest revealed small bilateral pneumothorax (2 cm and 5mm) along with extensive ground-glass opacifications in all lobes. In the next 24 hours, the right-sided pneumothorax progressed to tension pneumothorax requiring pigtail pleural drainage catheter placement. The drained pleural fluid had more than 100,000/uL total nucleated cells (91% neutrophils, 2% lymphocytes, and 1% eosinophils) and ultimately cultures grew Rhizopus spp. He was started on intravenous liposomal amphotericin-B infusion (5 mg/kg daily). On hospital discharge, he was switched to oral posaconazole (started with loading 300 mg delayed-release tablet twice a day, followed by 300 mg dosing of delayed-release posaconazole tablets daily) to complete the long term treatment course. DISCUSSION: Most of the reported cases of mucormycosis in COVID-19 were in patients with either diabetes or receiving steroids. This is a rare presentation of COVID-19–associated pulmonary mucormycosis (CAPM) as spontaneous pneumothorax, in the absence of known immunosuppression history. COVID-19 results in a considerable increase in cytokines, particularly interleukin-6 (IL-6), which increase free iron by increasing ferritin levels due to increased synthesis and decreased iron transport. Also, concomitant acidosis increases free iron by reducing the ability of transferrin to chelate iron and this available iron becomes a considerable resource for mucormycosis. [1] Also, Mucorales adheres to and invades endothelial cells by specific recognition of the host receptor glucose-regulator protein 78 (GRP-78). Acidosis associated with severe COVID-19 triggers GRP-78 and fungal ligand spore coating homolog (CotH) protein expression on endothelial cells, both contributing to angioinvasion, hematogenous dissemination, and tissue necrosis. [2] CONCLUSIONS: Mucormycosis can present as spontaneous pneumothorax after recent COVID-19 and clinicians should be aware of rare clinical presentation. Reference #1: Singh AK, Singh R, Joshi SR, et al. Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes Metab Syndr Clin Res Rev 2021;15:102146. doi:10.1016/j.dsx.2021.05.019 Reference #2: Baldin C, Ibrahim AS. Molecular mechanisms of mucormycosis—The bitter and the sweet. PLOS Pathog 2017;13:e1006408. doi:10.1371/journal.ppat.1006408 DISCLOSURES: No relevant relationships by Faran Ahmad No relevant relationships by AYESHA BATOOL No relevant relationships by Zachary DePew No relevant relationships by Neil Mendoza

Immune-mediated Acute Limb Ischemia: A Rare Complication of SARS-CoV-19 Infection

Occurrence of acute limb ischaemia (ALI) in patients with SARS-CoV-2 is an uncommon complication. COVID-19 has been associated with thrombotic disease secondary to a hypercoagulable state. COVID-19 appears to cause a hypercoagulable state through mechanisms unique to SARS-CoV-2 and centres on the cross-talk between thrombosis and inflammation. The proposed hypothesis includes a severely heightened inflammatory response that leads to thrombotic inflammation, through a mechanism such as cytokine storm, complement activation, and endothelitis. The innate and adaptive immune responses result in immunemediated thrombosis, leading to thrombotic complications, such as myocardial infarction, pulmonary embolism, deep vein thrombosis, and stroke. The activation of coagulation (D-dimer) and thrombocytopenia are important prognostic markers in SARSCoV- 19 infections. At our institution, we found six patients to have ALI and reviewed their characteristics and outcomes. Our findings showed that in severe COVID-19 disease, the association of ALI had high mortality. Materials and methods: It is a retrospective observational study performed at Bangalore Baptist hospital during the COVID-19 pandemic (August 2020 to August 2021). We report a case series of 6 ALI patients aged between 30 and 55 years. All the patients were tested positive for SARS-CoV-2 disease. All our patients received standard treatment care as per institution protocol for SARS-CoV-2 disease. They were all commenced on therapeutic anticoagulation at admission to ICU. Baseline coagulation profile and inflammatory markers and their trends were followed in all patients. The diagnosis of ALI in all ventilated patients was done clinically by the presence of pallor, pulselessness, acrocyanosis, blisters, and dry care unit with SARS-CoV-2 disease, 6 patients had developed limb ischemia (1.4%). Male and female preponderance was equal. Among 6 patients, 1 was newly detected diabetes mellitus, 2 were diabetic and hypertensive of which one had right upper limb post-polio paralytic sequelae, and the rest had no co-morbidities. The mean duration of ICU stay and mechanical ventilation days was 22 days and 17.8 days, respectively. All the patients had lower limb ischemia of which 3 were unilateral. Discoloration extended up to the ankle joint in almost all cases. As these patients were on the ventilator secondary to severe hypoxemia or vasopressor support, they were managed conservatively. Two patients presented with stroke, pyelonephritis with acute kidney injury, and septic shock requiring high vasopressor support. 5 of 6 patients died during the course of treatment (mortality 83%). All patients showed high inflammatory markers especially D-dimer during the initial development phase of limb ischemia. 1 survived patient required bilateral foot amputation due to dry gangrene. Conclusion: Limb ischemia with tissue necrosis is a dreadful complication and is associated with high mortality. High incidence of thrombosis despite therapeutic anticoagulation raises a question about pathophysiology unique to COVID-19. Evidence of inflammatory-mediated thrombosis and endothelial injury are possible explanations which would support the use of immunotherapy in addition to anticoagulation for the treatment of thrombotic events. Further insight into the cause and management of thrombosis is needed.

CLINICAL STUDY OF COVID ASSOCIATED RHINO-ORBITAL MUCOR MYCOSIS IN STATE COVID HOSPITAL

Background: Mucormycosis is one such infection which has shown a sudden rise during the second wave in India. (Our present study has been designed to all the confirmed cases of rhino orbital mucormycosis. In our study we have included all the rhinorbital mucormycosis cases that have been confirmed by microscopy and or radiological evidence.Mucormycosis (also called zygomycosis) is a serious fungal infection caused by agroup of molds called mucoromycetes. Materials and Methods: All the patients that have directly attended the ophthalmology OPD. Chief complaint with duration (Look for redness, watering, discharge & pain in the eye, diplopia, eyelid/ periocular swelling) facial swelling, eyelid/perioculay facial discoloration, Worsening headache, sudden drooping of eyelid (or) restricted eye movements, sudden loss of vision, facial parasthesia / anaesthesia, nasal discharge (blakish/ bloody/foul smell nasal stuffiness, dental pain. Results: Out of all 60 cases, 79 there were 47 males and 13 females. In this study 48.33% cases belongs to age group of 50-60 years followed by 36.66% belongs to age group of 60-70 years. Among the 60 patients who presented to hospital within 1 week of onset of symptoms likee pain redness watering et 35 of them got good vision, whereas among the 15 members who presented beyond 2 weeks after the onset of their symptoms only 7 got good vision while 2 of them got poor vision below 6/60 indicating the importance of early diagnosis. 65% cases affected at right eye and 63.33% cases showing symotoms like Redness, treatment under goes with total Restriction 42 members and Painful oculr movement in 43.33% cases. Conclusion: The second wave of COVID-19 in India has led to more deaths than the first. In just a few weeks, the B.1.617.2 (Delta) variant became the dominant strain across India. It has since spread to about 40 nations, which include United Kingdom, Fiji and Singapore.18 the first case of Covid-19-related Mucormycosis has now been found in Chile. It is important to recognise at an early stage this infection, so as to potentially reduce soft and hard tissue necrosis and severe complications and alert colleagues of this mutilating and life threatening infection.

Rare Bilateral Invasive Pulmonary Mucormycosis with Tracheo-Esophageal Fistula and Left Mainstem Bronchus Disruption

Introduction: Mucormycosis is a rare invasive opportunistic fungal infection caused by Zygomycetes. [1,2] It is associated with worse outcomes in immunocompromised patients.[3,4] Invasive pulmonary infections can lead to bronchial necrosis from angioinvasion.[1,3] Here, we present a case of invasive pulmonary mucormycosis (IPM) caused by Rhizopus spp, resulting in tracheo-esophageal fistula. Case : An 18-year-old male with uncontrolled type 1 diabetes was admitted to the intensive care unit for diabetic ketoacidosis (DKA) and acute hypoxia due to COVID 19 pneumonia requiring ventilatory support. Chest imaging showed bilateral opacities. He was treated with dexamethasone for COVID 19 and broad-spectrum antibiotics for superimposed bacterial pneumonia. Clinical course was complicated by acute respiratory distress syndrome and pneumomediastinum. Computed tomography of the chest showed large pneumomediastinum with air leak within the distal thoracic trachea. Bronchoscopy revealed a disfigured main carina with erosions (figure 1), a tracheo-esophageal fistula, necrotic blood-tinged left mainstem bronchus tissue, and a necrotic pus-filled superior segment of the right lower lobe. Left mainstem bronchial tissue specimen culture grew Rhizopus and Klebsiella spp. Liposomal amphotericin was initiated. Given his poor prognosis, the patient's family refused aggressive thoracic surgical intervention and pursued palliative care. Discussion: Rhizopus spp is the most common cause of mucormycosis in immunocompromised populations.[6] IPM is the second most common clinical form reported after the central nervous system.[3,6] Typically, IPM lesions are localized, and invasive presentations are infrequent. Rarely, IPM can cause invasive disease by angioinvasion, obstructing blood flow, and ischemic tissue necrosis.[6] Airway tissue necrosis can lead to fistulas between the airway and adjacent structures, including pleura, pericardium, and mediastinum.[2,3,4,5] Published clinical literature review revealed only a few cases due to IPM. Common predisposing factors include diabetes, DKA, and immunosuppressive medications, as observed in our patient.[3] Lobar bronchi are the usual locations of endobronchial erosions, with a predilection for the upper lobes.[3] In contrast, the left mainstem bronchus and right lower lobe were involved in the case presented here. In addition to antifungal treatment, surgical debridement is the mainstay of therapy due to necrosis.[7] The survival rate is between 35-46% in medically managed compared to 51-90% in surgically treated patients.[3]Conclusion: IPM is a life-threatening invasive disease associated with high mortality rates. Clinicians should suspect it in immunocompromised patients, including diabetes. The clinical history may include uncontrolled diabetes, recent DKA, and infections predisposing patients to develop superimposed fungal infections. The concurrent use of systemic steroids may also contribute to worse outcomes. (Figure Presented).

Review of etiopathogenesis and Early diagnosis of Mucormycosis

Mucormycosis refers to invasive fungal disease whose causative organism are saprophytic fungi. Recently there has been an outbreak of mucor in post covid cases. It is a fatal disease until properly intervened.The literature regarding mucormycosis is scarce. There is urgent need to understand the aetiopathogeneis and clinical features of mucormycosis. This article helps to comprehensively understand the etiopathogenesis in patients having mucormycosis. This narrative review is an attempt to comprehend aetiopathogeneis and early diagnostic features in mucormycosis.Literature on various aspects of mucormycosis was collected from various search engines like pubmed, Google scholar. Various phrases used were mucormycosis, etiology, pathogenesis diagnosis.Various risk factors associated with this disease are use of corticosteroids, metabolic acidosis, diabetes mellitus, burns organ transplants, malignancies and various haematological disorders. Nososcomial infections mostly due to non sterility is proving to be a kajor risk factor has in mucormycosis. Immunocompromised patients are at a greater risk for acquiring infection however few reports of mucormycosis in immunocompetent patients have been published. Angioinvasion leads to thrombosis followed by necrosis of the tissue hampering drug delivery to the target tissue. Angio invasion is the single most important factor explaining pathology.Early diagnosis and intervention is the only key way to treat mucormycosis patients as early diagnosis will help in early treatment and that ultimately decrease angioinvasion and less extensive surgeries. Traditional cultural method can be used for early diagnosis but it has a higher possibility false negative results. Few clinical signs that may help in early diagnosis can be necrotic eschars in various mucosal surfaces, pleuritic pain, ophthalmic symptoms are important markers. Though these clinical signs help, they may present after long time. So imaging techniques like CT scan and MRI have a really important part in early diagnosis. MRI is more sensitive for tthe diagnosis of invasive fungal sinusitis than CT and it also gives less false negative results.