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Purpose: Invasive fungal infection (IFI) complicating Coronavirus disease of 2019 (COVID-19) has been increasingly recognized. IFI is a common opportunistic infection in solid organ transplant (SOT), but association with COVID-19 is unknown. Method(s): This was a retrospective study of all SOT recipients hospitalized with COVID-19 between March 2020 and Oct 2021. IFI was defined based on EORTC/ MSG criteria. Result(s): 107 SOT recipients were hospitalized due to COVID-19. 17 patients were excluded because they were on a systemic antifungal agent on admission. Median age was 62 yrs. 46% were female. 59% (53) were recipients of kidney, 17% (15) of lung, 11% (10) each of heart and liver, and 2% (10) of small bowel. 8% (7) of patients developed IFI within 90 days of COVID-19 (2 proven and 5 probable) (Table): 3 due to yeasts (2 bloodstream and 1 lung), and 4 pulmonary aspergillosis. Median time from COVID-19 diagnosis to IFI was 22 days (1d to 78d). Mechanical ventilation (P = 0.01) and augmented immunosuppression (p = 0.04) were risk factors for IFI;receipt of dexamethasone or IL-6 inhibitor were not risk factors. IFI associated with more prolonged hospital stay (median of 23 days (7-120d) vs 10d (1-80d), respectively). The 90-day mortality after COVID-19 diagnosis was 23% (21), higher for patients with IFI (57% vs 20%;p=0.04). By univariate analysis, the risk factors for death were: use of dexamethasone (p=0.011), IL-6 inhibitor (p=0.001), and IFI (p=0.049);SARS-CoV-2 monoclonal antibody (Mab) was protective (p=0.06). By multivariate analysis, receipt of IL-6 inhibitor (p=0.001) and IFI (p=0.009) were independent risk factors for death;Mab was protective (p=0.02). Overall, 18% (16) patients received systemic antifungals (AF);11% (9) received AFs without any IFI diagnosis and they all received anti-mold agents. Conclusion(s): The incidence of IFI complicating COVID-19 was 8%, and IFI was associated with a higher mortality. The association between receipt of IL-6 inhibitor and death among SOT patients is of concern. Risk and benefit of this agent along with it's side effect should be carefully evaluated in larger trials of SOT and other immunosuppressed COVID-19 patients. (Table Presented).
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SESSION TITLE: Severe and Unusual Blastomycosis Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: The diagnosis of blastomycosis is often delayed due to its non-specific symptoms and imaging findings. Clinicians must have a high clinical index of suspicion to diagnose blastomycosis in a timely manner, especially in the setting of the current COVID-19 pandemic. CASE PRESENTATION: A healthy 44-year-old male presented to an urgent care center with complaints of cough, fevers, and malaise. CT scan of the chest revealed a left upper lobe mass concerning for rounded bacterial pneumonia versus malignancy. He was found to be COVID-19 positive. The patient was sent home with steroids and antibiotics. Three months later, a repeat CT scan of the chest was obtained which revealed progression of the consolidation and prompted further evaluation at the hospital. On presentation, he reported a persistent cough, weight loss, and the development of multiple painful nodules on his extremities and trunk within the past week. A skin lesion was biopsied. A bronchoscopy was also performed for biopsy and brushing. Biopsy of the skin lesion as well as specimens collected from the bronchoscopy resulted positive for Blastomyces. MRI of the brain demonstrated multiple enhancing lesions concerning for septic emboli. He was started on amphotericin B for treatment of disseminated blastomycosis with central nervous system (CNS) involvement. Repeat imaging of the brain and chest about 3 weeks after initiation of therapy showed interval decrease in the size of the lesions. He was then transitioned to oral itraconazole and discharged home. DISCUSSION: Blastomycosis is an endemic fungal infection that can affect immunocompetent and immunocompromised hosts. It tends to infect immunocompetent hosts more so than other invasive fungal infections. Symptoms can range from asymptomatic to rapidly progressive acute respiratory distress syndrome (ARDS). Disseminated blastomycosis has been reported in 20-50% of patients (1). In the above case, an immunocompetent patient developed pulmonary and dermatologic manifestations concerning for disseminated blastomycosis. Though he had no recent travel, occupational exposures, or contact with any construction work, the patient was living in an endemic area for Blastomyces. It is difficult to definitively ascertain if the patient already had pulmonary blastomycosis when he was diagnosed with COVID-19, but his extrapulmonary manifestations clearly developed after the diagnosis. Earlier detection and treatment of the pulmonary blastomycosis may have prevented the dissemination of the disease. CONCLUSIONS: This case serves as a reminder to consider other infectious etiologies, like endemic fungal infections, in the midst of the COVID-19 pandemic to prevent delays in treatment and progression of these diseases. Reference #1: McBride JA, Gauthier GM, Klein BS. Clinical Manifestations and Treatment of Blastomycosis. Clin Chest Med. 2017 Sep;38(3):435-449. doi: 10.1016/j.ccm.2017.04.006. Epub 2017 Jun 12. PMID: 28797487;PMCID: PMC5657236. Reference #2: Cafardi J, Haas D, Lamarre T, Feinberg J. Opportunistic Fungal Infection Associated With COVID-19. Open Forum Infect Dis. 2021 Jan 18;8(7):ofab016. doi: 10.1093/ofid/ofab016. PMID: 34621913;PMCID: PMC7928619. DISCLOSURES: No relevant relationships by Shannon Burke No relevant relationships by Abigail Go No relevant relationships by Jen Minoff No relevant relationships by David Stoeckel
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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
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SESSION TITLE: COVID-19: Other Considerations in Management SESSION TYPE: Original Investigations PRESENTED ON: 10/18/2022 02:45 pm - 03:45 pm PURPOSE: Since its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has spread across the world, claiming millions of lives. With the publication of RECOVERY trial and REMAP-CAP trial, tocilizumab is recommended as additional therapy in select COVID populations by various professional societies. Although not observed initially in several randomized trials, concerns regarding serious secondary infections have been raised. Hereby, we seek to describe the epidemiology of infectious complications after tocilizumab in COVID patients admitted to a tertiary community hospital and to determine related risk factors for infections. METHODS: A retrospective cohort study was conducted among COVID patients requiring noninvasive or invasive ventilation who received tocilizumab at our hospital between June 2020 to December 2021. We define infectious complications as positive culture grown on a specimen that was also treated with antibiotics by the primary team. Baseline demographics and laboratory values are obtained through electronic medical records. Continuous outcomes are analyzed with parametric and non-parametric testing. Categorical variables are analyzed using the Chi-Square test. Risk factors are identified through Probit regression analysis and stepwise analysis. Statistics are performed using SPSS and STATA. RESULTS: 52 patients are identified with a median age of 63 and 46.2% female sex. Median hospital admission time since COVID diagnosis is 2 days and median tocilizumab administered time is 6.5 days. Common comorbidities include hypertension (63.5%), hyperlipidemia (50%) and diabetes (44.2%). Infectious complications are documented in 30 patients (57.7%), with 29 episodes of pneumonia, 7 episodes of urinary tract infection, and 4 episodes of bacteremia. Common organisms include MSSA (21%), Pseudomonas aeruginosa (19%), Klebsiella species (13%) and MRSA (5%). There are 9 cases of multidrug-resistant bacterial infection and 3 episodes of invasive fungal infection (1 Candidemia and 2 invasive aspergilloses). 22 patients (43.3%) died in the hospital before discharge with a median alive time after tocilizumab of 16.5 days. Hyperglycemia on admission (defined as a random glucose >200 mg/dl), hypertension and antibiotic use before tocilizumab are independent risk factors associated with infectious complications during regression analysis. Age >65 is the single most significant factor associated with death in the hospital. CONCLUSIONS: In real-world experience, infectious complications are not uncommon in COVID patients who receive tocilizumab. Our analyses show that potential risk factors for developing infections include a history of hypertension, hyperglycemia on admission and antibiotic use before tocilizumab. CLINICAL IMPLICATIONS: More rigorous criteria in patient selection and patient monitoring should be explored in future trials involving tocilizumab in COVID patients. DISCLOSURES: No relevant relationships by Zauraiz Anjum No relevant relationships by Ming-Yan Chow No relevant relationships by Ahmed Elkhapery No relevant relationships by Hafsa Faisal No relevant relationships by Lakshmi G Nair No relevant relationships by Charoo Iyer No relevant relationships by Hongli Liu No relevant relationships by Chengu Niu No relevant relationships by Kaiwen Zhu
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SESSION TITLE: Global Pulmonary Cases SESSION TYPE: Global Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: COVID 19 is associated with hyper- inflammation with levels of IL 6 correlating with the severity of COVID 19. IL6 causes increased vascular permeability and endothelial dysfunction and plays a major role in the development of ARDS.[1] Tocilizumab is a monoclonal antibody against the IL6 receptor which is being used for COVID pneumonia. Large randomized controlled trials including REMAP-CAP and RECOVERY reported a mortality benefit of tocilizumab in certain patients [3]. Aspergillus is a mold that causes variety of pulmonary infections depending on host's immune status. In immunocompromised hosts, it causes invasive pulmonary aspergillosis [2]. Symptoms initially are similar to bronchopneumonia: cough with sputum, dyspnea, fever not responsive to antibiotics. With disease progression, patients experience pleuritic chest pain and hemoptysis. CASE PRESENTATION: 69 y/o female came to ER with complaint of dyspnea and cough. PMH significant for Diabetes. She had a recent admission for COVID 3 weeks ago during which she received tocilizumab. This time, her vitals were HR- 96 RR- 24 Temp- 99.6 BP- 124/72, Sat- 88% on 2L NC. Labs WBC 31.1 D dimer- 2.17 ABG PO2- 61. CT pulmonary angiogram was consistent with left mid lung zone cavitary mass with an air-fluid level measuring 5 x 8 cm in transverse and AP dimension. Patient was started on broad-spectrum antibiotics (vancomycin, cefepime, metronidazole). Sputum cultures, Beta glucan assay, AFB and fungal immunodiffusion panel was ordered. Beta D Glucan assay came positive. Fungal immunodiffusion panel was negative. Bronchoscopy was done and AFB, aspergillus antigen and cultures were collected. BAL aspergillus antigen came positive and KOH fungal culture grew Aspergillus Fumigatus. Voriconazole was started. She was discharged on voriconazole for 12 weeks, ceftriaxone and clindamycin for 6 weeks for antibacterial coverage with plan to repeat CT chest in 3 weeks. DISCUSSION: We use tocilizumab for COVID 19 patients requiring invasive or non invasive mechanical ventilation and CRP ≥7.5 and exclude patients with ANC <2000, platelet <50,000 and history of serious bacterial, fungal or viral infection. This patient did not have any exclusion criteria but developed invasive fungal infection 3-4 weeks later. Due to worsening hypoxia and high D dimer, initial consideration was pulmonary embolism for which CT angiogram was done and a cavitary lesion was found. Differentials were bacterial abscess, tuberculosis or fungal infection. BAL played a crucial role in diagnosing aspergillosis. CONCLUSIONS: In patients presenting with worsening respiratory symptoms post tocilizumab administration we must keep a low index of suspicion for superimposed opportunistic infections including aspergillosis. Appropriate workup including CT chest, sputum or bronchoalveolar lavage for cultures (bacterial, fungal), Beta D Glucan and fungal panel is essential for diagnosis. Reference #1: Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia Ivan O Rosas;Norbert Bräu;Michael Waters;et al. New England Journal of Medicine, v384 n16 (20210422): 1503-1516 Reference #2: Pulmonary aspergillosis: a clinical review M. Kousha, R. Tadi, A.O. Soubani European Respiratory Review 2011 20: 156-174;DOI: 10.1183/09059180.00001011 Reference #3: Interleukin-6 Inhibitors. Available at: https://www.covid19treatmentguidelines.nih.gov. DISCLOSURES: No relevant relationships by Shaylika Chauhan No relevant relationships by Vipul Gidwani
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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
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Background: The COVID- 19 infections are associated with wide range of bacterial and fungal co-infections. They may be associated with various comorbidities. Definite diagnosis requires demonstration of fungi in tissue sections or in culture. Yield of organism in culture is suboptimal. Hence histopathology plays critical role in establishing the diagnosis and provide evidence of tissue invasion. Objective(s): To study the histopathological features of fungal infections in sino nasal, oral and orbital area associated with COVID-19 patients. Material(s) and Method(s): One hundred twenty cases of fungal infections involving sinonasal, oral and orbital area in laboratory confirmed COVID-19 positive patients between June-September 2021 were taken for study. Clinical data was recorded, histopathological examination was done along with periodic acid Schiff stain and culture report was obtained. Result(s): The study included 92(76.6%) males and 28(23.3%) females with age ranging from 13 to 78 years. The tissues included debridement, biopsy and excision specimen. Acute inflammation was seen in 8(6.66%) cases, chronic inflammation in 112(93.33%), granulomas in 25, thrombosis in 14, necrosis in 104, angioinvasion in 13, perineuritis in 10 and bone invasion in 18 cases. Mixed fungal infection was seen in 11cases. Conclusion(s): Histopathology remains the mainstay in diagnosis of invasive fungal infections especially when culture is negative. Copyright © 2022 Ubiquity Press. All rights reserved.
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Invasive fungal infections (IFI) are associated with high rates of morbidity and mortality, and immunocompromised hosts are often affected. Candida albicans is among the main cause of IFIs in the last decades, and Paracoccidioides brasiliensis is found in most of the IFIs identified in the South America. Rhizopus oryzae causes mucormycosis that increased in the COVID-19 pandemic. Host immune response against IFIs depend of the effector activity of T cells, which is compromised in immunodeficient patients. However, chimeric antigen receptor (CAR) technology can redirect T cells to target any antigen inducing the cell activation, which can be applied in immunocompromised patient as done in cell therapy against cancer. We developed a CAR (M-CAR) specific to a carbohydrate on the fungal cell wall, and Jurkat cells expressing M-CAR after lentiviral transduction using a multiplicity of infection (MOI) of 1, 3, 5 or 10 had its recognition capacity evaluated against C. albicans, P. brasiliensis, and R. oryzae. CAR expression increased in a MOI dependent-manner, and M-CAR Jurkat cells produced high levels of IL-2 in the presence of hyphae form of C. albicans,P. brasiliensis yeast, and R. oryzae spores. These findings evidenced the capacity of M-CAR to recognize these fungi inducing T cell activation. This work opened new perspectives to evaluate the fungicidal activity of human T and NK cells expressing M-CAR in response to species of fungi studied. Keywords: Chimeric Antigen Receptor (CAR), T cells, invasive fungal infections.
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Background: Bing-Neel syndrome (BNS) is a rare complication of lymphoplasmacytic lymphoma (LPL) comprising LPL infiltration in the central nervous system (CNS). Clinical and radiological features are diverse;the diagnosis is confirmed by cerebrospinal fluid (CSF) analysis using immunological and molecular techniques. Rarely, a tissue biopsy is required. The pattern of presentation including systemic involvement and CSF features inform treatment strategies, which include CNS-penetrating therapies. Aims: To evaluate the diagnostic characteristics of patients with BNS and their influence on therapy. Methods: Data from patients referred between 2011-2021 for management of BNS to our academic neurohaematology centre were retrospectively reviewed. Those with imaging features alone or where it was not possible to distinguish from high-grade transformation were excluded. Results: Thirty-five patients (22 male, 13 female) were identified. Median age at diagnosis of BNS was 65 years (range 48-85). All patients were symptomatic. In 12 patients (34%) BNS was the de novo presentation of the IgM-related disorder, of which 3 (25%) had no detectable bone marrow (BM) infiltration of LPL at diagnosis. Approximately half (17;49%) had previously received therapy for LPL;median time to BNS diagnosis in these was 49 months (range 3-125). At BNS diagnosis, BM involvement with LPL ranged from 0-95%. More than half (14/26;54%) had <10% infiltrate and almost a fifth (4/26) >60%. All patients had leptomeningeal involvement and 8 (23%) additionally had parenchymal CNS disease. The majority had kappa light-chain predominance: IgMκ (n=26), non-IgMκ (n=5), IgMλ (n=3), one unknown. The BNS diagnosis was made on CSF analysis (n=28;80%), leptomeningeal tissue biopsy (n=3;9%) where CSF was non-informative, or by expert opinion based on supportive clinical, radiological and non-definitive CSF features (n=4;11%). Of those with a diagnosis based on CSF studies, B-cell clonality was confirmed by flow cytometry (27/28;96%), MYD88L265P mutation (18/28;64%) and immunoglobulin gene rearrangement (12/28;43%). In 22 samples with a full dataset, median CSF white cell count was 25/ul (1-233), CSF protein 1.69g/l (0.35-6), CSF IgM 9.49mg/l (1.07-61.5). The majority were treated with intensive regimens (rituximab, methotrexate (MTX), cytarabine (ARA-C) + thiotepa/idarubicin;n=30) due to the presence of CNS disease bulk and clinical need, and less commonly ibrutinib (n=3), bendamustine-rituximab (BR, n=1);one patient had intrathecal therapy (MTX, ARA-C) at the height of the COVID pandemic. Of those who received 2 cycles of intensive chemotherapy, 3 had >4 cycles followed by BCNU/thiotepa autologous stem cell transplant;10 proceeded to 'consolidation' (indefinite) ibrutinib to limit intensive chemotherapy or tackle systemic disease. At a median follow up of 26 months (range 1-121), median survival was not reached;2-year overall survival was 91% (95% CI 74-97). Three patients died during treatment (1 invasive fungal infection post COVID-19 during ibrutinib consolidation post MTX/ARA-C based therapy) and 2 during MTX-ARA-C based therapy;7 patients relapsed or progressed and were treated with ibrutinib: 1 relapsed after ibrutinib use, 1 patient was intolerant of ibrutinib and switched to BR. Image: Summary/Conclusion: Our cohort confirms that BNS may present with leptomeningeal disease and/or parenchymal disease, de novo and without systemic disease. Overall outcomes are excellent with intensive regimens, consolidated with or followed by ibrutinib;however, there are treatment-related toxicities emphasising the need for a tailored approach.
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Background: On 2019, the FDA and later the EMA granted approval to polatuzumab vedotin-piiq, a CD79b-directed antibodydrug conjugate indicated in combination with bendamustine and rituximab (P-BR) for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), after at least two prior therapies. P-BR has demonstrated (NCT02257567) better overall response rates (complete and partial responses) compared with BR alone (63% vs 25%) and response durations of at least 12 months in 48% of the patients. The most common adverse reactions with P-BR (incidence at least 20%) included cytopenias (most common reason for treatment discontinuation), peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite and pneumonia. Serious adverse reactions occurred in 64%, most often from infection. Aims: To analyze results in terms of efficacy and safety of the P-BR regimen in real life conditions. Methods: Observational, retrospective study in 3 academic centers. Adult patients (≥ 18 years old) diagnosed with DLBCL NOS R/R who received P-BR between July 2019 and December 2021 were included in the analysis. Results: 11 patients were treated with P-BR. The mean (SD) age was 70.1 (8.2) years (Range 57-81 years). Cell of origin was informed in 9/11 cases, 6 of them were activated B-cell (ABC) subtype. No double-/triple-hit lymphomas were confirmed. The median number of prior lines of therapy before P-BR was 2, with most patients (63%) refractory to the last treatment. All patients had received anti-CD20 (Rituximab) on prior treatments and only 2 (18%) Bendamustine. Baseline characteristics are shown in table 1. Efficacy Seven patients were evaluated by PET-CT after 3 cycles, 4 (57%) achieved CR and 3 PR (43%). Five patients achieved CR by PET-CT at the end of treatment. One of these patients is still in CR after 12 months of follow up and three of them after 24 months from the start of P-BR. One patient relapsed after 19 months. Of the patients achieving CR, all of them had responses >12 months. Only 3/5 completed the 6 cycles scheme, 1 patient received 5 cycles (treatment was interrupted due to an invasive fungal infection) and 1 patient received only 2 cycles as bridge therapy for and autoHCT and achieved CR after transplantation. 1 patient was refractory to treatment and progressed after 2 cycles. Toxicity: All patients were evaluated for toxicity. 63% (7/11) of them presented hematological toxicity, mainly neutropenia which required GCSF administration and 71% RBC transfusion. Two patients required hospital admission because of neutropenic fever. There were 3 documented cases of SARS-CoV-2 infection. Two patients had moderate disease with bilateral pneumonia (vaccinated) after the 2° cycle of treatment which is temporarily interrupted. One patient completed 6 cycles but died of severe SARS-CoV2 infection (unvaccinated) before being assessed for response at end of treatment. Two patients interrupted treatment definitely because of toxicity: severe cytopenia and invasive fungal infection. No other extra hematological toxicities were reported. Image: Summary/Conclusion: The P-BR regimen provides sustained good results for patients with R/R DLBCL who have failed treatment with prior therapies. Cytopenias were the most frequent form of toxicity and were easily addressed in most cases. In our experience, SARS-CoV2 infection has been a challenge due to delay in treatment and high morbidity and mortality.
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Aim and background: Mechanical Power in ARDS has predictive value for both VILI and mortality. Driving pressure and mechanical power are two new targets in the mechanical ventilation of ARDS patients. COVID-19 pneumonia has two different phenotypes H type and L type which have different lung compliance, elasticity, and recrutability with different ventilatory strategies. We want to observe how Mechanical Power behaves in H type COVID-19 ARDS and its correlation with compliance and driving pressure. Objective: To study the correlation of Mechanical Power with Driving Pressure and Compliance in H type of COVID-19 pneumonia. Materials and methods: It is a prospective observational study conducted in COVID-19 patients admitted to the Medical Intensive Care unit. We included 65 adult COVID-19 patients aged between 18 and 70 years requiring invasive mechanical ventilation for at least 24 hours. Patients who developed spontaneous pneumothorax and pneumomediastinum before initiation of mechanical ventilation were excluded. Patients were categorised to H type based on lung compliance (<40 mL/cmH2O), recrutability, and lung weight. The Mechanical Power was calculated using the following equation, MP = 0.098 × TV × RR (Paw-1/2 ΔP). Paw-peak airway pressure, ΔP-driving pressure, TV-tidal volume, RR-respiratory rate. The variables are taken at 3 different time intervals in the first 24 hours of invasive mechanical ventilation. All patients are ventilated according to ARDSNET protocol. The Driving pressure and compliance were recorded. The correlation of Mechanical Power with Driving pressure and Compliance were analysed using Pearson Correlation. Results: The mean age of the patients was 57.04 ± 13.96 years (mean ± SD), gender distribution 75% were males and 25% were females. A positive correlation was observed between Mechanical power and Driving pressure (Pearson correlation 0.245) which is statistically significant p = 0.049. A negative correlation was observed between Mechanical power and Compliance (Pearson correlation 0.183) which is not statistically significant. Conclusion: The Mechanical Power and Driving pressure the new targets of Ventilator-Induced Lung Injury (VILI) and also predictors of mortality in ARDS patients. The positive correlation between Mechanical Power and Driving pressure was observed in H type of COVID-19 patients which behaves similar to other ARDS and independent risk factors of mortality in H type of COVID-19 ARDS too.
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The currently prevalent COVID-19 infection, its line of treatment, resultant immunosuppression, and pre-existing comorbidities have made patients exposed to secondary infections including mucormycosis. Mucormycosis is a rare but in invasive fungal infection (IFI) due to several species of saprophytic fungi, occurring in patients with underlying co-morbidities which include diabetes mellitus, organ transplant, immunosuppressive corticosteroid therapy. The maxilla rarely undergoes necrosis due to its rich vascularity. Rare but not uncommon is the incidence of mucormycosis associated maxillary osteomyelitis occurring post COVID-19 infection. Fungal osteomyelitis is a life-threatening infection which may further spread from maxilla to the nose and paranasal sinuses within the orofacial region. It is an aggressive infection that needs to be addressed promptly to prevent fatal consequences.
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Systemic mycoses are fungal diseases attacking the body through an internal organ. They are the cause of increasing morbidity rates, especially among the immunocompromised population (e.g. with HIV), but also exist as a co-infection in patients with COVID-19. Nowadays, the 'life-saving/last chance' drug (and a poison to humans), Amphotericin B (AmB), is the representative of nonaromatic heptaene macrolides. However, previously obtained data indicate significantly higher antifungal activity of the aromatic heptaene subgroup (AHM), which is unfortunately correlated with their high mammalian toxicity. The undertaken studies concern Partricin and Candicidin complexes as the main representatives of AHMs. Three aromatic heptaene macrolides: Partricin A, Partricin B and Candicidin D were isolated from fermentation broths of S. aureofaciens and S. griseus, respectively, by initial purification, followed by selected chromatographic techniques such as centrifugal partitioning chromatography (CPC) and prep-HPLC. Later on, they were subjected to controlled chromophore geometry change (cis-trans to all-trans) via photochemical isomerization, using UV light of k = 365 nm. The obtained all-trans isomers, regarded as aromatic analogues of AmB, were tested for in vitro selective toxicity indexes (STIs) towards C. albicans cells versus human erythrocyte model. Due to the diminished hemotoxicity of the all-trans isomers - which were maintaining most of their fungicidal power - the obtained STIs were very promising and far better than for AmB (previously published in: J.Górska et al. (2021) Int. J. Mol. Sci. 22). Hence, the all-trans AHMs bear a great potential to be weaponized on the antifungal battlefield. Nevertheless, since individual AHMs are commercially unavailable and difficult to obtain due to their complex nature, our studies will focus on facilitation of the isolation process and further improvement of their STIs, mainly through rational, structural modifications.
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Introduction / Case Presentation:46yo female with a history of CKD, atrial flutter, bioprosthetic valve with mitral ring, and recent COVID-19 pneumonia who presented to the emergency department (ED) with shortness of breath, fevers, and fatigue. Three months prior, she had been diagnosed with severe COVID-19 pneumonia, for which she received dexamethasone, remdesivir, tocilizumab, anakinra, and IVIG. She was discharged to a nursing facility with a prolonged steroid taper, ending 1 month prior to admission.In the ED, the patient had a chest x-ray that demonstrated bibasilar atelectasis and opacification, and a CT chest revealed right lower lobe consolidation and surrounding ground glass opacities. A respiratory pathogen PCR swab was negative. Sputum culture was negative for bacterial and fungal growth. Blood cultures did not grow any organisms. Given recent immunosuppression and imaging findings, a serum Cryptococcal antigen was drawn, which was positive with a titer of 1:128. A transthoracic needle biopsy of the patient's right lower lung was then performed. The specimen did not grow any bacteria or fungi and AFB stain on the tissue was negative. Pathology demonstrated a collection of histiocytes, neutrophils, and necrotic debris. PAS, GMS, and mucicarmine stains were positive for fungal organisms consistent with Cryptococcus species. Discussion: Cryptococcosis is a fungal infection due predominately to one of two encapsulated yeasts, Cryptococcus neoformans or Cryptococcus gattii. C. neoformans is found in soil worldwide, and infection typically begins with spore inhalation. Clinically significant disease is seen mostly in immunocompromised patients.Corticosteroids and interleukin inhibitors, such as anakinra (IL-1) and tocilizumab (IL-6), are used in the treatment of COVID-19. These medications have been associated with increased risk for opportunistic infections, including invasive fungal infections. The diagnosis of pulmonary cryptococcosis may be challenging, as symptoms are often nonspecific and may radiographically resemble bacterial pneumonia, malignancy, or other infections. Serum cryptococcal antigen detection tests may be helpful in establishing the diagnosis, as well as histopathology showing narrow-based budding yeast. Conclusion: Patients with prior COVID-19 infection commonly return to healthcare settings with sequelae of their previous coronavirus infection. In our case, it was the prior treatment of COVID-19, which included immunomodulating therapy, that lead to a secondary pulmonary cryptococcal infection. When evaluating pulmonary processes that evolve after an acute infection with COVID-19, it is important to keep a broad differential, including uncommon and/or opportunistic infectious etiologies, particularly when a patient has received prolonged courses of steroids and tocilizumab.
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Infectious diseases caused by fungi (mycoses) are one of the significant problems of modern medicine Worldwide, more than 300 million people suffer from severe and chronic mycoses, 25 million patients are at risk of disability or death. Due to changes in treatment strategies and the wider use of antifungal prevention in recent years, the epidemiology of fungal infections has changed and has become particularly relevant due to a significant increase in cases of invasive mycoses. Deep, visceral mycoses, sometimes associated with HIV infection, oncohematological pathology, organ transplantation, nursing of newborns, have become more frequent, while the role of fungi that were previously considered apatogenic increases. In the context of the COVID-19 pandemic, risk factors for these infections continue to increase, and therefore it is likely that the incidence of fungal infections, including those associated as nosocomial, will increase in the coming years. The increasing role of fungi in the etiology of hospital infections, the introduction into clinical practice of a significant number of new drugs was inevitably accompanied by the formation of resistance of fungi to antimycotics. According to literature data, the rate of emergence of pathogenic fungi resistant to a limited number of widely used antifungal agents is unprecedented. Thus, in modern conditions associated with the increase in resistance of pathogenic fungi, the key measures should be aimed at developing optimal strategies for containing resistance to antifungal drugs.
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Background: Invasive fungal infections are an important cause of morbidity and mortality in immunocompromised patients. These infections remain difficult to diagnose and their management is complicated by their aggressive course of disease. Discussion: A 50yrs old female, case of rheumatoid arthritis on treatment, post covid presented in a state of DKA with complaints of fever, cough, breathlessness and right sided pleuritic chest pain for >1 month with 2-3 episodes of minimal hemoptysis. CXR s/o Right middle lobe cavity lesion. Bronchoscopy: Right UL bronchial segments inflamed, irregular sloughed mucosa with endobronchial narrowing, biopsy obtained. HPE s/o mucormycosis Patient started on IV antibiotics & antifungals. Thoracotomy- Right upper and middle lobectomy done on day 8 of hospitalization. Right upper lobe had two large necrotic thick walled cavities with blackish slough. On post-op day 4 patient developed large air leak in ICD s/o BPF. Second thoracotomy for BPF repair done after 7weeks of 1stsurgery. Patient had respiratory distress after extubation. CXR showed right opaque hemithorax with pull of mediastinum. Required urgent bronchoscopy to remove endobronchial mucus plug. Conclusion: Prognosis and outcome have improved as a result of early diagnosis, newer antifungals agents & surgical debridement. Antifungal treatment, surgical interventions & high risk of post surgical complications in an immunocompromised elderly host is grave challenge. But our case had a positive clinical outcome.
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Background: Fungal epidemic was announced amid COVID pandemic with several cases of COVID-associated Mucormycosis and Aspergillosis being reported however there is not sufficient data regarding mixed fungal infection. Case Study: A 54-year-old male patient diagnosed with severe COVID 19 pneumonia and diabetes 1-month back presented to OPD with C/O of chest pain and breathlessness for two days associated with haemoptysis, heaviness and congestion of right nostril but no fever. O/E patient was tachypnoeic, hypoxic and in shock, Neutrophil count 87%, RBS-530 mg/dl, urine ketone body was absent. Chest x-ray showed opacity over the left upper and mid-zone, HRCTthorax showed a bird-nest-sign noted in the left upper lobe S/O invasive fungal infection. MRI PNS showed mucosal thickening S/O sinusitis, Fungal infection. Sino-nasal mucosa KHO-mount and fungal culture showed mixed infection of Rhizopus species and aspergillus flavus. Right nasal HP study showed mixed invasive moulds infection. Initially, the patient was treated conservatively later on inj. amphotericin-B was started. The patient's condition worsened on day-18 and succumbed a day later. Discussion: Uncontrolled diabetes-mellitus, and corticosteroids leading to hyperglycaemia, extensive use of broad-spectrum antibiotics increases the risk of invasive Moulds. In our case study, patients suffered from COVIDpneumonitis and had uncontrolled diabetes leading to damage of airway epithelium inviting an invasion of tissues by moulds. Conclusion: Mixed fungal infections as COVID-19 sequelae may be an emerging issue and seen particularly in post- COVID patients with uncontrolled diabetes, and on steroids. The focus should be on prompt management: hit hard approach with both medical and surgical treatment.
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Introduction: Mucormycosis is an emerging angioinvasive infection caused by the ubiquitous filamentous fungi of the mucorales order of the class of zygomycetes. It has emerged as one of the most common invasive mycosis in patient with hematological and allogeneic stem cell transplantation. It also remains threat in diabetic and also recently in post covid patients. Case Report: A 62 year old male farmer patient came with complaints of cough with expectoration, fever, moderate hemoptysis and headache. Patient is having uncontrolled diabetes mellitus. All routine blood investigations and coagulation profile was normal. CECT Thorax suggestive of ring like opacities with areas of ground glass opacities surrounded by ring of consolidation suggestive of fungal pneumonia. Simultaneously patient is having severe throbbing headache. So MRI brain with orbit and paranasal sinus done, which suggestive of ethamoidal sinusitis ,osteomyelitis of clivus. Hence IV antifungal amphotericin b started as immediate measure in a view of disseminated fungal infection with strict glycemic control. Sputum smear, microscopy, bacterial culture, gene xpert are negative. Lung biopsy done which suggestive of branching ribbon like hyphae. Hence patient posted for right upper lobectomy. Patient discharged on Tab. Posaconazole. Patient came follow up after 3 months , symptomatically improved and radiological resolution of lesions of chest xray. Conclusion: Mucormycosis is a life threatening infection, and usually the diagnosis late because of nonspecific clinical ,radiological features and need biopsy for confirmation of the organism. The cornerstone for the management and increase the survival rate remain on rapid diagnosis ,treatment of the underlying predisposing condition and urgent surgical debridement.
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Objective: The purpose of this study was to evaluate the change in clinical spectrum and outcomes of invasive fungal disease involving the anterior skull base region. Study Design: This study represents a retrospective review of the patients diagnosed with acute and chronic invasive fungal rhinosinusitis based on imaging, fungal staining and culture, biochemical analysis, and histopathology report. Assessment of anterior, central skull base including orbital involvement was done clinicoradiologically and/or intraoperative findings. Setting: A tertiary referral hospital. Results: There was a total of 79 patients, of which 67% had skull base mucormycosis, 33% had invasive aspergillosis. In the skull base mucormycosis group, there were 53 patients, with 33 males and 20 females. 88% of patients had a history of COVID-19 infection. 98% of patients had type 2 diabetes mellitus. The mean duration of symptoms was 36 days, and 68% of them presented 30 days after onset of symptom. Mortality was seen in 7 (14%) patients. The most common symptom of the presentation was facial swelling followed by facial numbness, vision loss and headache. The most common area of skull base involved was pterygopalatine fossa (88%), followed by infratemporal fossa (71%), anterior and posterior cribriform area (60% each). The most common vessel involved was the sphenopalatine artery (75%), and the neural structure involved was infraorbital nerve (64%) and maxillary division of trigeminal nerve (52%). 13 patients had an intracranial disease, with 2 having cerebritis and rest with parenchymal abscess including one patient with cerebellar abscess. All patients had radical debridement with antifungal treatment. In the invasive aspergillosis group, there were 26 patients with 12 males and 14 females with a mean age of 42 years. The mean duration of presentation after the onset of the symptom was 33 weeks. Only 26% of patients had diabetes mellitus (type 2), and one patient had COVID-associated aspergillosis who presented within 28 days after onset of symptom with intracranial extension. Tissue diagnosis for confirmation of aspergillosis was obtained in 62% of patients, while the use of galactomannan assay and clinicoradiological diagnosis was done in 38%. A similar trend of skull base involvement was seen.
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Background: One of the largest outbreaks of rhinosinocerebral mucormycosis (RSCM) occurred in India close to the second wave of the SARS-CoV-2 infection. RSCM is a rare infection caused by several fungal species occurring in immunocompromised subjects. Mucor shows a high propensity to invade the central nervous system. There have been limited studies, mostly isolated case reports, on the neurological manifestations of RSCM. The outbreak of mucormycosis infection was thus the most opportune to study the neurological manifestations and cranial nerve involvement in mucormycosis in greater depths. Aim of the study: The purpose of the study was to investigate and review the involvement of cranial nerves in a series of cases of rhinosinocerebral mucormycosis associated with the novel coronavirus disease caused by SARS-CoV-2. Results: It was a retrospective cross-sectional study of seven patients who were undergoing treatment of RSCM with a recent history of coronavirus disease caused by SARS-CoV-2 infection within the last 3 months. Patients with cranial nerve involvement were identified by magnetic resonance imaging (MRI) at a single institution. Demographic details of the patients, clinical presentation, imaging, microbiological and pathological findings were recorded. All subjects had two or more cranial nerves affected by fungal infection. The most commonly involved cranial nerve was found to be the optic nerve followed by the trigeminal nerve and its branches. We document three cases with extensive involvement of the inferior alveolar branch of the mandibular division of the trigeminal nerve (V3), a previously unreported finding. In one case, in addition to the second and fifth cranial nerves, the third, fourth, sixth, seventh, eighth, and twelfth cranial nerves were involved without any sensory or motor long tract involvement, suggestive of Garcin syndrome secondary to intracranial abscesses and skull base osteomyelitis due to invasive fungal infection. This case is of rare occurrence in the literature, and our study provides one such example. Conclusion: Cranial nerve involvement in patients of mucormycosis tends to have a poor prognosis, both cosmetic and functional. Radical surgeries and aggressive medical management is needed in such cases to improve the outcome.