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      Covid-19-associated fungal osteomyelitis of jaws and sinuses: An experience-driven management protocol

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          Abstract

          Invasive fungal co-infections with COVID-19 are currently being reported at an alarming rate. Our study explores the importance of early identification of the disease, probable etiopathogenesis, clinical and radiological features and a treatment protocol for COVID-19 Associated Fungal Osteomyelitis of Jaws and Sinuses (CAFOJS). A one-year prospective study from June 2020 to May 2021 was conducted among CAFOJS diagnosed patients at a tertiary care center in South India. Demographic details, COVID-19 infection and treatment history, time taken for initiation of symptoms after COVID-19 diagnosis, medical history and clinical features were recorded. All patients were managed with a standard diagnostic and intervention protocol which included pre-operative and post-operative administration of Inj. Amphotericin B 50 mg (liposomal), early aggressive surgical debridement and tab. Posaconazole GR 300 mg OD for 90 days after discharge. Thirty-nine (78%) patients were diagnosed with CAFOJS out of 50 osteomyelitis patients. 35 patients (90%) were diabetic and 21 patients (54%) were known to receive steroids during the COVID-19 treatment. Sole existence of Mucorales spp. was seen in 30 patients (77%), Aspergillus fumigatus in 2 patients (5%), Curvularia spp. in 2 patients (5%). Concomitant existence of Mucorales and Aspergillus fumigatus was reported in two patients (5%) and Candida albicans in three patients (8%). Patients underwent treatment with standard protocol and no recurrence noted. CAFOJS is a clinical entity with aggressive presentation and warrants early diagnosis and treatment.

          Lay summary

          Invasive fungal infections of head and neck region cause necrosis of bones affected by it, especially maxilla. Early diagnosis and treatment are advocated in such infections due to its aggressive clinical presentation compared to similar infections before COVID-19 pandemic.

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          Most cited references15

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          Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium

          Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.
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            Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes

            Multiple organ damage in severe acute respiratory syndrome (SARS) patients is common; however, the pathogenesis remains controversial. This study was to determine whether the damage was correlated with expression of the SARS coronavirus receptor, angiotensin converting enzyme 2 (ACE2), in different organs, especially in the endocrine tissues of the pancreas, and to elucidate the pathogenesis of glucose intolerance in SARS patients. The effect of clinical variables on survival was estimated in 135 SARS patients who died, 385 hospitalized SARS patients who survived, and 19 patients with non-SARS pneumonia. A total of 39 SARS patients who had no previous diabetes and received no steroid treatment were compared to 39 matched healthy siblings during a 3-year follow-up period. The pattern of SARS coronavirus receptor-ACE2 proteins in different human organs was also studied. Significant elevations in oxygen saturation, serum creatinine, lactate dehydrogenase, creatine kinase MB isoenzyme, and fasting plasma glucose (FPG), but not in alanine transaminase were predictors for death. Abundant ACE2 immunostaining was found in lung, kidney, heart, and islets of pancreas, but not in hepatocytes. Twenty of the 39 followed-up patients were diabetic during hospitalization. After 3 years, only two of these patients had diabetes. Compared with their non-SARS siblings, these patients exhibited no significant differences in FPG, postprandial glucose (PPG), and insulin levels. The organ involvements of SARS correlated with organ expression of ACE2. The localization of ACE2 expression in the endocrine part of the pancreas suggests that SARS coronavirus enters islets using ACE2 as its receptor and damages islets causing acute diabetes.
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              Global Epidemiology of Mucormycosis

              Mucormycosis is an angio-invasive fungal infection, associated with high morbidity and mortality. A change in the epidemiology of mucormycosis has been observed in recent years with the rise in incidence, new causative agents and susceptible population. The rise has been perceived globally, but it is very high in the Asian continent. Though diabetes mellitus overshadow all other risk factors in Asia, post-tuberculosis and chronic renal failure have emerged as new risk groups. The rhino-cerebral form of mucormycosis is most commonly seen in patients with diabetes mellitus, whereas, pulmonary mucormycosis in patients with haematological malignancy and transplant recipients. In immunocompetent hosts, cutaneous mucormycosis is commonly seen following trauma. The intriguing clinical entity, isolated renal mucormycosis in immunocompetent patients is only reported from China and India. A new clinical entity, indolent mucormycosis in nasal sinuses, is recently recognized. The causative agents of mucormycosis vary across different geographic locations. Though Rhizopus arrhizus is the most common agent isolated worldwide, Apophysomyces variabilis is predominant in Asia and Lichtheimia species in Europe. The new causative agents, Rhizopus homothallicus, Mucor irregularis, and Thamnostylum lucknowense are reported from Asia. In conclusion, with the change in epidemiology of mucormycosis country-wise studies are warranted to estimate disease burden in different risk groups, analyse the clinical disease pattern and identify the new etiological agents.
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                Author and article information

                Contributors
                Journal
                Med Mycol
                Med Mycol
                mmy
                Medical Mycology
                Oxford University Press
                1369-3786
                1460-2709
                February 2022
                24 January 2022
                24 January 2022
                : 60
                : 2
                : myab082
                Affiliations
                Assistant Professor, Department of Oral and Maxillofacial Surgery, SDM Craniofacial Surgery and Research Centre, SDM College of Dental Sciences and Hospital, A Constituent Unit of Shri Dharmasthala Manjunatheshwara University , Dharwad, 580009, Karnataka, India
                Additional Professor, Department of Oral and Maxillofacial Surgery, SDM Craniofacial Surgery and Research Centre, SDM College of Dental Sciences and Hospital, A Constituent Unit of Shri Dharmasthala Manjunatheshwara University , Dharwad, 580009, Karnataka, India
                Professor and Head, Department of Oral and Maxillofacial Surgery, SDM Craniofacial Surgery and Research Centre, SDM College of Dental Sciences and Hospital, A Constituent Unit of Shri Dharmasthala Manjunatheshwara University , Dharwad, 580009, Karnataka, India
                Resident, Department of Oral and Maxillofacial Surgery, SDM Craniofacial Surgery and Research Centre, SDM College of Dental Sciences and Hospital, A Constituent Unit of Shri Dharmasthala Manjunatheshwara University , Dharwad, 580009, Karnataka, India
                Resident, Department of Oral and Maxillofacial Surgery, SDM Craniofacial Surgery and Research Centre, SDM College of Dental Sciences and Hospital, A Constituent Unit of Shri Dharmasthala Manjunatheshwara University , Dharwad, 580009, Karnataka, India
                Assistant Professor, Department of Microbiology, SDM College of Medical Sciences and Hospital, A Constituent Unit of Shri Dharmasthala Manjunatheshwara University , Dharwad, 580009, Karnataka, India
                Professor and Head, Department of Microbiology, SDM College of Medical Sciences and Hospital, A Constituent Unit of Shri Dharmasthala Manjunatheshwara University , Dharwad, 580009, Karnataka, India
                Professor and Head, Department of Plastic and Reconstructive Surgery, SDM College of Medical Sciences and Hospital, A Constituent Unit of Shri Dharmasthala Manjunatheshwara University , Dharwad, 580009, Karnataka, India
                Author notes
                To whom correspondence should be addressed. Amal Suresh, Department of Oral and Maxillofacial Surgery, SDM Craniofacial Surgery and Research Centre, SDM College of Dental Sciences and Hospital, A Constituent Unit of Shri Dharmasthala Manjunatheshwara University, Dharwad, 580009, Karnataka, India. Tel: +91 9686721200; E-mail: dramalsuresh@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-9239-9930
                Article
                myab082
                10.1093/mmy/myab082
                8822410
                35076069
                dfd5b64b-4c16-44d4-9fba-7fde1c7cd549
                © The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.

                This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                : 24 June 2021
                : 16 December 2021
                : 22 December 2021
                Page count
                Pages: 9
                Categories
                Original Article
                AcademicSubjects/MED00010
                AcademicSubjects/SCI00960

                Infectious disease & Microbiology
                fungal osteomyelitis,covid-19,mucormycosis,curvalaria,aspergillosis,maxillectomy

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