NK CELLS ARE CRITICAL FOR IN VIVO CONTROL OF SARS-CoV-2 REPLICATION AND DISEASE

Background: Natural killer (NK) cells play a critical role in control of viral infections. However, empirical evidence thus far has been unclear on the role of NK cells in pathogenesis and control of SARS-CoV-2 infection with some research suggesting NK cell accumulation as beneficial while others indicate it as deleterious. To address this crucial deficit in understanding, we employed a non-human primate infection model with a validated experimental NK cell depletion technique. Method(s): A total of 12 experimentally naive (75% female) cynomolgus macaques (CM) of Cambodian origin were used in this study. Six CM were NK cell-depleted using an anti-IL-15 neutralizing antibody, while six controls received placebo, prior to intranasal and intratracheal challenge with the SARS-CoV-2 Delta variant at a TCID50 of 1X105. The cohort was monitored for five weeks with scheduled blood, colorectal (CR) biopsies, and lymph node (LN) collections. Total envelope and sub-genomic viral loads (VL) were measured in the nasal cavity, throat, and bronchoalveolar lavage (BAL). 23-color flow cytometry, pathology, and 27-plex inflammatory analyte Luminex analyses were conducted. Statistical tests used were Mann-Whitney U and Spearman's Correlation. Result(s): Control CM exhibited an increase in the frequency of circulating NK cells, reaching a peak at 10 days post-infection (DPI) and returning to baseline by 22DPI. Simultaneously, NK cells expressing activation and tissue retention marker, CD69, also significantly increased. Cytotoxic NK cells were positively associated with VL (r=0.66;p=0.02), suggestive of a virus-induced mobilization. Total experimental NK cell ablation was verified in blood, CR, and LN of NK celldepleted CM, which had higher VL compared to controls in all tissues evaluated, reaching significance at 10DPI (p=0.01) and demonstrated a longer duration of viremia. Although Luminex measures were similar in plasma, BAL samples from NK cell-depleted CM had universally higher concentrations of inflammatory mediators, most notably a 25-fold higher concentration of IFN-alpha compared to controls. Lung pathology scores were also higher in NK cell-depleted CM with increased evidence of fibrosis, syncytia, pneumocyte hyperplasia, and endothelialitis. Conclusion(s): Overall, we find significant and conclusive evidence for NK cell-mediated control of SARS-CoV-2 virus replication and disease pathology. These data suggest adjunct therapies for infection could largely benefit from NK cell-targeted approaches.

Futuristic Rehabilitation Technique Of Acquired Maxillectomy Defect In Post Covid19 Mucormycosis Using Polyether Ether Ketone Obturator Prosthesis- A Case Report

Background: Oroantral communication can occur due to maxillectomy defects, jeopardizing the integrity and function of oral cavity. It is an interdisciplinary challenge to restore these by surgery and prosthetics since many facets need to be addressed, such as speech, deglutition, mastication, aesthetics and psychological distress. Rationale: Surgical repair of maxillectomy defects is not always achievable due to various reasons such as poor systemic health, advanced age etc. Thus prosthetic rehabilitation becomes the most suitable treatment option. Relevance for Patients: Post COVID-19 mucormycosis has seen a surge in the past two years. It is an opportunistic fungal infection in humans infecting intracranial structures by direct invasion in the blood stream. Fundamental goal of prosthetic rehabilitation is the closure of oronasal communication and restoring it functionally thereby improving quality of life for the patient. CAD/CAM (computer aided design/computer aided milling) technology was employed to fabricate a milled framework for maxillary obturator in the most innovative way using PEEK (Polyether ether ketone). Result(s): PEEK material due to its excellent biocompatibility ensured a light weight prosthesis for the large maxillectomy defect and closure of the patency was achieved by the obturator framework.Copyright © 2022 Authors. All rights reserved.

Pioneering wound treatment in a suffragette military hospital in World War 1

In the face of massive numbers of casualties returning to the UK in World War 1, health services were rapidly reorganized under the leadership of Sir Alfred Keogh. Hundreds of military hospitals were set up. Sir Alfred personally asked two women doctors, both militant suffragettes and members of the British Women's Social and Political Union, to set up and run a hospital in London. This remarkable hospital was to pioneer new antiseptic treatments for wounds. Endell Street Military Hospital was set up in 1915 by doctors Flora Murray and Louisa Garrett Anderson. The hospital was staffed and run solely by women, treating 26 000 patients in 520 beds over the course of the war. One of their most heroic contributions was to the care of wounds in injured soldiers returning from France. Throughout the war wound infections led to the deaths of thousands of soldiers and contributed to significant morbidity such as limb loss in countless others. In 1916 James Rutherford Morrison, Professor of Surgery in Durham, invented bismuth iodoform paste (BIPP) for the treatment of wound infections. The paste has significant antimicrobial properties. The Endell Street doctors contacted Morrison in June 1916 and started using his formulation on injured patients. By early 1917 they had treated > 400 patients with gunshot wounds, compound fractures, septic wounds, through-and-through wounds and foreign body wounds with BIPP, reporting their findings in The Lancet (Garrett Anderson L, Chambers H. The treatment of septic wounds with bismuth-iodoform-paraffin paste. Lancet 1917;189: 331-3). They reported no cases of tetanus or gas gangrene and were able to explain side-effects such as iodine and bismuth poisoning, why it occurred and how it could be avoided. BIPP has been in use constantly since 1916, and is still used today in ear, nose and throat departments, especially for packing nasal cavities. By changing from the traditional eusol (sodium hypochlorite solution) to BIPP Drs Murray and Anderson reduced dressing changes from daily to once every 7-14 days, saving staff time, costs and hugely improving outcomes. These women doctors saved hundreds of lives and pioneered wound treatments that are still used today. Both were awarded the CBE for their services, but sadly the hospital staff were sacked at the end of the war, when the hospital closed. This form of pioneering work, conducted under great strain with limited resources is still to be seen today in the COVID-19 pandemic.

Simultaneous Primary Sinonasal Adenocarcinoma and Breast Adenocarcinoma: A Case Report

Sinonasal cancer accounts for roughly only 3% of upper respiratory tract malignancies and generally presents as a primary malignancy. Although extremely rare, the sinonasal cavity is also a known location for metastasis, with 8% of these cases originating from primary breast cancer. When attempting to differentiate primary disease from metastasis, immunohistochemical analyses play a crucial role in reaching the correct diagnosis. To date, there are a handful of reports describing metastasis involving the paranasal sinuses but even fewer reporting primary sinonasal cancer with coexisting primary malignancy. Here we present a case of primary sinonasal adenocarcinoma in the setting of a long-standing history of breast cancer. The patient, a 73-year-old female, was diagnosed with T1cN1aM0, progesterone receptor positive and estrogen receptor negative ductal carcinoma in situ of the left breast in November 2019. She subsequently underwent bilateral mastectomy and treated with 3 cycles of chemotherapy and anastrozole, which were both discontinued due to intolerance. Of note, in March 2019, MRI of the head incidentally found a 3 x 2 cm mass in right nasal cavity extending into ethmoid sinus. One year later, she presented with mild right sided nasal obstruction and drainage, and biopsy revealed squamous and respiratory mucosa with chronic inflammation. The patient elected to cancel initial surgical resection of the mass due to the COVID-19 pandemic. The patient returned in March 2022 with complaints of eye pressure, double vision, headaches, and worsening nasal obstruction. PET/CT scan was negative for distant metastasis but demonstrated increased uptake in sinus cavity. MRI showed a larger 5 x 3.7 cm mass impressing on medial inferior margins of orbit. Imaging also suggested evidence of dehiscence of lamina and irregular neo-osteogenesis of the skull base. She underwent approach and resection of the mass with histology demonstrating a well differentiated, low grade non-intestinal mucinous adenocarcinoma. Immunohistochemistry was positive for pankeratin and CK7, favoring a primary sinonasal origin. It was estrogen receptor negative and negative for GATA3, a sensitive and fairly specific stain in mammary carcinoma. Adjuvant radiation was recommended postoperatively, however the patient declined this therapy. This case highlights the role of immunohistochemistry to discriminate a new primary cancer from metastasis in patients with a history of breast cancer. Clinically, patients with sinonasal metastasis can present with symptoms ranging from unilateral nasal obstruction, facial pain, diplopia, and decreased vision. On imaging, suspicion of malignancy is raised when there is evidence of destruction of bony boundaries and invasion of surrounding tissues such as the orbit and anterior skull base, as found in our patient. Notably, metastasis to the paranasal sinuses can mimic a primary cancer of the nasal cavity, with both tumors showing epithelial differentiation. However, primary tumors often show neoplastic changes in the overlying respiratory epithelium and do not express estrogen receptor, progesterone receptor, or HER2 positivity, which are known to be correlated with breast cancer. In this setting, GATA3 and estrogen receptor negativity allowed us to diagnose primary nasal cancer more confidently. Therefore, clinicians should be aware of metastatic disease and expand immunohistochemistry panels when appropriate.

Relationship Between the Nasopharyngeal Swab Sampling Method, Nasal Obstruction, and SARS-Cov-2 Positivity

Aim: We think that the nasopharyngeal swab sample should be taken bilaterally to improve the sensitivity of the real-time-reverse transcriptase-polymerase chain reaction (RT-PCR) test since there may be pathologies that cause nasal obstruction, such as nasal septum deviation (NSD). In this context, we investigated the effect of the nasopharyngeal swab sampling method and the presence of nasal obstruction on the detection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Method(s): This prospective clinical study was conducted from March 2021 to January 2022. Forty-four hospitalized patients with NSD were included in the study group, and 44 hospitalized patients without NSD were included in the control group. The results of the RT-PCR test studied with a unilateral nasopharyngeal swab sample taken during hospitalization and the RT-PCR test studied with a bilateral nasopharyngeal swab sample taken on the 2nd day of hospitalization and the visual analog scale (VAS) scores showing the patients' pain during the first sampling were determined. Result(s): In the first test, 23 (52.3%) patients in the study group and 32 (72.7%) patients in the control group were evaluated as SARS-CoV-2 positive. The first test sensitivity was significantly higher in the control group (p=0.048). The VAS score was significantly higher in the study group (p=0.00008). In the second test, 35 (79.5%) patients in the study group and 37 (84.1%) patients in the control group were evaluated as SARS-CoV-2 positive. The sensitivity increases in the study group and in the population were statistically significant (p=0.007 and p=0.004, respectively). The consistency of the first and second test results increased in patients without NSD and in patients with low VAS scores [odds ratio (OR)=3.779;p=0.001, OR=2.572;p=0.005, respectively]. Conclusion(s): Nasopharyngeal swab sampling may be affected by nasal congestion and the sampling method. To avoid this, it may be more appropriate to take a nasopharyngeal swab sample through the bilateral nasal cavity. Copyright © 2022 by The Medical Bulletin of Istanbul Haseki Training and Research Hospital The Medical Bulletin of Haseki published by Galenos Yayinevi.

RADIOLOGICAL SPECTRUM OF SINONASAL MUCORMYCOSIS IN COVID POSITIVE PATIENTS

Rationale and Objectives-At present, sinonasal mucormycosis is most worrisome COVID-19 related complication in India while western countries have relatively stayed aloof. But given the pervasive nature of fungi and presence of all predisposing conditions even in western countries, it is imperative to have knowledge about the imaging patterns and staging of the disease. In this study, we try to single out factors responsible for the sudden increment in the incidence of sinonasal mucormycosis among covid-19 patients and discuss their imaging features. Patients and Methods-The case records of 30 patients, between January to May, 2021, with positive RT-PCR for COVID-19 and biopsy proven sinonasal mucormycosis were retrospectively evaluated. Results – Out of 30 patients, 28 had raised random blood glucose level and 24 had raised ferritin level. On imaging, nasal cavity involvement was seen in 18 patients. Paranasal sinuses were involved in 28 patients. The disease process also showed involvement of orbit, neck spaces and intracranial extension. We divided sinonasal mucormycosis into four groups and mortality was seen in patients of stage 3 and 4 (total mortality was 26.7%). Conclusion-MRI played an important role in diagnosis and staging of sinonasal mucormycosis as well as determining the extrasinus extent of disease. Mortality was seen in patients presenting in advanced stage of the disease, with orbital or intracranial extension. Thus, it is imperative that high index of suspicion, early imaging with diagnosis and aggressive management protocol needed to reduce morbidity and mortality.

DON'T LOSE SIGHT OF GPA

CASE: A 48-year-old female with no medical history presented with 2 days of decreased vision in the right eye. She reported painless blurry vision that progressed to near complete vision loss. The vision loss was accompanied by one month of progressively worsening cough, body aches, and subjective fevers. She denied smoking and reported no sick contacts. Physical exam was notable for submandibular lymphadenopathy, bilateral conjunctival injection, and grossly decreased vision of the right eye. She also endorsed decreased sensation in bilateral lower extremities distally. Her initial labs showed leukocytosis (13), thrombocytosis (754), and elevated inflammatory markers (ESR 105 and CPR 359). A chest CT showed bilateral upper lobe consolidations and scattered mass like opacities bilaterally. Ophthalmic exam of the right eye revealed multiple small retinal infarctions consistent with paracentral acute middle maculopathy. A CT head was negative and TTE showed no vegetation. Additional testing revealed negative TB, COVID, and normal complements. Initial ANCA testing was negative, however a repeat test was strongly positive for ANCA with PR3 significantly elevated to 428. She was diagnosed with granulomatosis with polyangiitis (GPA) vasculitis and treated with prednisone and started induction therapy of Rituximab. IMPACT/DISCUSSION: GPA is a small-medium vessel necrotizing vasculitis and the most common anti-neutrophil- cytoplasmic-antibody (ANCA) associated vasculitis. GPA classically involves the upper respiratory tract, lungs, and kidneys referenced by the ELK criteria (ENT, Lung, Kidney) commonly used for diagnosis. ENT findings are present in 70-100% of cases with the nasal cavity and paranasal sinuses most commonly involved. Roughly 50% have pulmonary involvement on presentation, as in this patient, while only 10-20% have initial renal involvement. A prodrome of systemic symptoms including body aches and fevers is often present. GPA is closely associated with c-ANCA, with autoantibodies to proteinase 3 (PR3) positive in over 80% of cases. This patient did have prodromal symptoms yet her primary presenting symptom of vision loss was atypical. Eye involvement is not part of the diagnostic triad yet it can occur in GPA. When it does present, it usually manifests as scleritis, conjunctivitis, or uveitis. Retinal infarctions, as seen in this patient, are uncommon and make this case an atypical presentation of GPA. Additionally, ANCA positivity is related to disease activity and a negative ANCA should not exclude GPA from a differential. Not all patients will be ANCA positive on initial presentation and 10% of patients with GPA will remain ANCA negative. CONCLUSION: Providers should consider atypical presentations of GPA in addition to the classic triad of ENT, Lungs, and Kidneys. Renal manifestations are often missing initially and involvement of other systems, such as ocular, can take place. With a positive c-ANCA and high clinical suspicion, treatment should not be delayed.

Neuroradiological profile of Rhinoorbitocerebral mucormycosis in COVID-19 pandemic

Objective: To study the radiological presentations of mucormycosis in the study cohorts.The patients were categorized as COVID-19 and diabetes millitus;COVID-19 and non-Diabetes;Non COVID-19 and non-diabetes and these cohorts were analysed. Background: There has been a recent surge of mucormycosis with COVID 19 infection particularly in patients with diabetes.Multicompartmental and extrasinonasal tissue infarction is possible without overt bone involvement and caused by the dissemination of fungal elements from the nasal cavity via perineural and perivascular routes.Fungal vasculitis results in internal carotid artery occlusion and cerebral infarction.Imaging features reflect the angioinvasive behavior of the Mucoraceae family, which cause necrotizing vasculitis and thrombosis resulting in extensive tissue infarction. Design/Methods: This was a Prospective observational study of Rhinoorbitocerebral mucormycosis cases presenting from May to July 2021 to our hospital.The clinical examination findings and neuroimaging features were assessed among the study cohorts. Results: Of the 544 patients the mean age of patients was 51.9 years with a male preponderance (71%).Uncontrolled hyperglycemia was present in 90% of all patients.Ethmoid sinus was the most common paranasal sinus involved by imaging( 86%).The most common site of extrasinus involvement was orbit (76%) and face (57%), followed by orbital apex, masticator space,pterygopalatine fossa.Intracranial extension with involvement of cavernous sinus was seen in 34% of patients, brain abscess(19.2%),internal carotid artery(17%),brain infarction(45.2%),meningeal thickening and enhancement(29.2%),bone and skull base(14%).The most common neuroradiological presentation seen in all cohorts was cavernous sinus thrombosis.The propensity for multiple cerebral abscess and skull base osteomyelitis was more in patients of Rhinoorbitocerebral mucormycosis with diabetes and COVID-19 cohort.Internal carotid artery involvement was predominantly seen in COVID-19 and non diabetic cohort.Limited sinonasal disease was more commonly seen in Non-COVID-19 and diabetes patients of mucormycosis Conclusions: Central to early diagnosis is a high index of suspicion by the clinician and the radiologist.The cavernous sinus was the most common site of intracranial involvement in our study.

Biosynthetic proteins targeting the SARS-CoV-2 spike as antivirals

The binding of the SARS-CoV-2 spike to angiotensin-converting enzyme 2 (ACE2) promotes virus entry into the cell. Targeting this interaction represents a promising strategy to generate antivirals. By screening a phage-display library of biosynthetic protein sequences build on a rigid alpha-helicoidal HEAT-like scaffold (named αReps), we selected candidates recognizing the spike receptor binding domain (RBD). Two of them (F9 and C2) bind the RBD with affinities in the nM range, displaying neutralisation activity in vitro and recognizing distinct sites, F9 overlapping the ACE2 binding motif. The F9-C2 fusion protein and a trivalent -Rep form (C2-foldon) display 0.1 nM affinities and EC50 of 8- 18 nM for neutralization of SARS-CoV-2. In hamsters, F9-C2 instillation in the nasal cavity before or during infections effectively reduced the replication of a SARS-CoV-2 strain harbouring the D614G mutation in the nasal epithelium and pathogenicity. Furthermore, F9-C2 and/or C2- foldon effectively neutralized SARS-CoV-2 variants (including delta and omicron variants) with EC50 values ranging from 13 to 32 nM. With their high stability and their high potency against SARS-CoV-2 variants, αReps provide a promising tool for SARS-CoV-2 therapeutics to target the nasal cavity and mitigate virus dissemination in the proximal environment.

Development and in vitro Evaluation of Atazanavir Microcrystals for Intranasal Delivery

Background: Nasal route of drug administration has gained popularity nowadays specially for drugs acting on nasopulmonary area. Atazanavir is an antiviral drug which has proved efficacy in different viral infection including COVID-19. Therefore the hypothesis is, if given through intra nasal route this formulation will be able to prevent the viral infection like COVID-19 by directly acting on the virus at its entry point. Objectives: This study aims to prepare a stable mucoadhesive microcrystal formulation of this antiviral drug with good permeation for intra nasal delivery. Materials and Methods: The formulation was prepared by high-speed homogenization process. Prepared microcrystals were estimated for in vitro drug release and permeation, drug excipient interaction study by DSC, FTIR and in vitro mucoadhesiveness study on agar gel plate. A short-term stability study was conducted on all formulations for 6 months. Results: The melting point and absorbance maxima of atazanavir were found as 200.9°C and 248 nm. The DSC and FTIR study results confirmed no drug excipient interaction was there in the formulation. The particle size of the formulations was found as 5-11 µm in range. Drug release was better and faster from the microcrystals as compare to pure powder drug. The flux for microcrystal formulation was found to be 100 whereas flux for the pure drug powder was 24. Formulations had sufficient mucoadhesive strength due to incorporation of HPMC 400 polymer and they were found stable after six months stability study. Conclusion: Lastly, it can be concluded that this formulation would be a promising system for the delivery through intra nasal route as it showed good drug release and permeation during a short time span in in vitro nasal condition with a particle size range suitable for intranasal delivery. However, further in vivo studies are required to confirm the hypothesis.

SPECTRUM OF CT FINDINGS IN CLINICALLY SUSPECTED CASES OF MUCORMYCOSIS - A STUDY AT TERTIARY HEALTH-CARE CENTER (RAJINDRA HOSPITAL PATIALA) DURING SECOND WAVE OF COVID PANDEMIC

Objective: Rhinocereberal mucormycosis is an acute, fulminant, and often lethal opportunistic infection typically affecting diabetic or immunocompromised patients. Early diagnosis is vital in these infections because delay in initiation of the treatment can be life-threatening. Computed tomography (CT) with axial and coronal sections is a highly accurate and non-invasive modality to accurately image sinonasal mycosis. The aim of the study was to describe the imaging findings in suspected cases of mucormycosis on CT. Methods: This study was conducted in Radiodiagnosis Department of Rajindra Hospital, Patiala. The data of 22 patients who were referred for CT with a clinical suspicion of mucormycosis were collected and all these patients were followed up to know about the prognosis of the disease. Results: In our study, there were 54.60% females and 45.40% males. Maximum number of patients (45.45%) belonged to 40-49 year age group. Diabetes mellitus was found to be the most commonly (90.90%) found comorbidity followed by hypertension (36.36%). In our study, involvement of unilateral nasal cavity was observed in 36.36% cases. Among the paranasal sinuses, maxillary and ethmoid sinuses were the most commonly involved in 95.45% and 77.27% cases. Conclusion: Prompt diagnosis and treatment of rhino-orbital mucormycosis are the sine qua non as antifungal drugs and surgical debridement can successfully control the infection and thus reduce the high mortality and morbidity associated with mucormycosis.

A pictorial review of imaging manifestations of rhino-orbito-cerebral mucormycosis–emerging threat in COVID pandemic

Mucormycosis is an aggressive invasive fungal infection caused by mycocetes fungi. It is an opportunistic infection, associated with high morbidity and mortality. In the current era of COVID-19 pandemic, the entire world has witnessed a dramatic upsurge in cases of Mucormycosis. Paranasal sinuses are the commonest site to be affected with the tendency for rapid spread to orbit, face, and brain. Early diagnosis and prompt medical or surgical intervention are the only ways for preventing morbidity and saving precious lives. Imaging plays a crucial role not only in diagnosis but also in defining the extent of the disease for presurgical mapping. Black turbinate sign in the nasal cavity, mucosal thickening in paranasal sinuses with periantral invasion, and bony erosion are the early diagnostic signs. This pictorial review shall provide a comprehensive review of the various imaging manifestations of rhino-orbito-cerebral mucormycosis with a final proposed reporting checklist.

COVID-19-Associated Acute Invasive Fungal Rhinosinusitis

Introduction: There have been multiple reports of acute invasive fungal rhinosinusitis (AIFRS) in patients with COVID-19 infection. Most cases were associated with high dose steroid therapy in diabetic patients. We report a case of a patient with COVID-19 infection and AIFRS. We will discuss management with the unique risks to the care team. Case: A 61-year-old diabetic woman was admitted to another facility with COVID-19 pneumonia and treated with oral dexamethasone. Three days later, she developed sharp stabbing pain in the right eye with ptosis and blurry vision. She was treated with analgesics and discharged. She returned with persistent pain and increasing right-sided hypesthesia. A CT scan did not show an acute orbital or sinus infection. She was discharged with outpatient ophthalmology follow-up. She presented to our emergency department 3 days later with 48 hours of right vision loss. Physical exam also showed disconjugate gaze and right V1/V2 hypesthesia. Nasal endoscopy showed necrotic tissue within the right nasal cavity. She was immediately started on IV amphotericin and taken to the operating room for biopsy and debridement. Pathology results were consistent with necrosis and invasive fungal hyphae. She was treated with liposomal amphotericin and was eventually discharged with permanent loss of right vision. Discussion: Management of COVID-19-associated acute invasive fungal sinusitis (CA-AIFRS) presents challenges for safety of the health care team. Diabetic COVID-19 patients' new sinonasal complaints or cranial nerve deficits must be immediately evaluated for AIFRS. The CT scan changes associated with AIFRS are nonspecific early in the disease process, therefore nasal endoscopy and biopsy are critical. This requires appropriate PPEnasal endoscopy should be performed with N95 respirator, eye protection, gloves, and a disposable gown. In patients with suspicious nasal endoscopy, immediate initiation of IV antifungals is critical. The next step is biopsy and surgical debridement. This should not be delayed in COVID-19 patients. At our institution, several steps are taken to protect the healthcare team. During intubation, only necessary anesthesia staff are in the roomwith properly worn powered air purifying respirator (PAPR). A viral filter is placed on the ET tube and the room doors are closed for 20 minutes after intubation to allow for air exchange. After 20 minutes, surgical staff may enter the room. The surgical team is outfitted with PAPRs. Powered instruments associated with aerosol generation such as high-speed drills are avoided. The surgical specimens are considered contaminated with COVID19. Therefore, frozen analysis is not used. Margins are sent for permanent analysis. Cultures are sent with appropriate labeling for laboratory precautions. The tissue is debrided to healthy tissue or natural barriers such as the skull base. Conclusion: Management of COVID-19 must include an awareness of CA-AIFRS. Diabetic patients on steroids appear to be more susceptible to CA-AIFRS. Nasal endoscopy is important for evaluation. Avoiding delays in starting antifungals and operative biopsy and debridement is critical. Safety considerations need to be prepared in advance for safe surgical debridement of these patients.

Curvularia Sinusitis in Leukemic Patients Two Case Reports and Review of the Literature

Curvularia species are dematiaceous filamentous fungi that can cause a variety of infections in both immunocompetent and immunocompromised hosts. We present 2 cases of severely immunosuppressed patients with acute invasive fungal sinusitis due to Curvularia species. Both patients had a history of hematologic malignancy with refractory disease and prolonged neutropenia. They presented with facial and sinus pain, which prompted maxillofacial computed tomography that showed acute sinusitis. Subsequently, they underwent nasal endoscopy with a biopsy that revealed a definitive diagnosis of invasive fungal sinusitis. Dematiaceous fungi are responsible for most fungal sinusitis cases, with Curvularia being one of the most common species isolated. Generally, invasive fungal rhinosinusitis may follow a relatively innocuous and nonspecific course. In addition, fungal infections may complicate chronic allergic sinusitis. Computed tomography scan is the first imaging modality of choice, and magnetic resonance imaging has a role in prognostication in acute invasive fungal rhinosinusitis. Endoscopic sinus surgery with biopsy yields a definitive diagnosis and is therapeutic. Management typically includes a combination of surgery and antifungal agents. Severe neutropenia is a significant risk factor for infection and is associated with poor outcomes. Aggressive surgical debridement, combined with antifungal therapy, should be emphasized in leukemic patients despite their prolonged neutropenia and bleeding tendency.

Radiologic Findings of COVID-19 Associated Mucormycosis (CAM) from India

Background. The unique feature of the second wave of the COVID -19 pandemic in India has been the alarming surge of acute invasive fungal infection among COVID -19 patients. The increased incidence of rhino-orbito-cerebral mucormycosis is a matter of concern, as this fulminant infection has high morbidity and mortality. Hence, it is imperative to understand it's imaging features, for early diagnosis, staging and treatment. Methods. We systematically reviewed 32 COVID-19 cases with imaging diagnosis of acute invasive fungal rhino-sinusitis or rhino-orbital-cerebral disease between March to May 2021. These patients underwent contrast MRI of the paranasal sinus, orbit and brain. Contrast enhanced CT chest and paranasal sinuses were done as needed. Results. The age group ranged between 30 to 71 yrs with male preponderance. The most common predisposing factors were intravenous steroid therapy and supplemental oxygen. All cases were confirmed by fungal culture and most common was Mucor. The rhino-orbito-cerebral mucormycosis was staged as below In our study we found that the most common site in the nasal cavity was the middle turbinate /meatus and the earliest sign was non-enhancing / "black" turbinate. Premaxillary and retroantral fat necrosis was the earliest sign of soft tissue invasion. Spread via the sphenopalatine foramen and pterygopalatine fossa was more common than bony erosions. Orbital cellulitis and optic neuritis were the most common among stage 3 cases. Of patients with CNS involvement, the most common were cavernous sinus thrombosis and trigeminal neuritis. Two patients with pulmonary mucormycosis showed large necrotic cavitary lesions, giving the characteristic "bird's nest" appearance. Conclusion. The mortality rate was 20% in our study. In our short term follow up, 30 % of recovered patients had relapse on imaging due to incomplete clearance and partial antifungal treatment. High clinical suspicion and low imaging threshold are vital for early Mucormycosis detection in COVID-19 patients. Familiarity with early imaging signs is critical to prevent associated morbidity /mortality. Axial CT chest image in lung window shows necrotic right upper lobe cavity with internal septations and debris on a background of surrounding COVID-19 changes.