Disseminated Mucormycosis in a patient on long term immunosuppression: Severe fungal infections as multi-system disorders

Introduction: Mucormycosis is a rare, severe fungal infection with an incidence of 0.005 to 0.17 per million.1 but incidence has risen recently, particularly in the Asian subcontinent, due to use of immunosuppression for Covid19.2 Presentations can vary and are classified into: rhino-orbito-cerebral, pulmonary, cutaneous, disseminated, renal and gastrointestinal. Risk factors include diabetes, immunosuppression, iron overload, malnutrition, and prematurity.1,3 Although mucormycosis has an extremely high mortality rate and disseminated infection is usually fatal, treatment options exist if diagnosed early and surgical debridement may be curative. Objective(s): We present a case of mucormycois in a female patient in her 40s who was immunosuppressed with methotrexate for rheumatoid disease. This case is discussed to increase awareness of critical illness caused by opportunistic invasive fungal infections in immunosuppressed patients and promote timely identification and management. Method(s): We detail the clinical context and management of a patient with mucormycosis and discuss relevant literature. Result(s): A female patient in her 40s who had been experiencing upper respiratory tract symptoms for several weeks, including cough and brown sputum, was admitted with a presumptive diagnosis of methotrexate toxicity after a full blood count performed by the general practitioner demonstrated pancytopenia. Initially, National Early Warning System 2 score (NEWS2) was 2 but became intensely hypertensive during blood transfusion and then profoundly shocked with an escalating NEWS2. Broad-spectrum antibiotics and fluconazole were commenced for neutropenic sepsis and the patient was referred to critical care in multiple organ failure. Computerised tomography (CT) scan of the chest, abdomen and pelvis showed "left upper lobe consolidation, which with neutropenia might represent an angioinvasive aspergillosis". She had multiple areas of skin discolouration and desquamation. Haematology and Infectious Diseases opinions were sought, and a bone marrow biopsy was performed which showed severe toxic effects consistent with sepsis/life threatening infection. Progressive proptosis was noted, and CT scan of her head was requested. Sadly, she was never stable enough for CT transfer. Beta D Glucan and aspergillus antigen serology was negative. Broncho-alveolar lavage demonstrated Candida albicans and then, later, Rhizopus arrhizus was isolated and anti-fungal treatment changed to voriconazole and then amphotericin B. Upon reviewing the notes in light of the positive culture for Rhizopus, the patient had likely been exhibiting symptomatic Mucormycosis sinus infection for some time prior to this admission with disseminated infection. The patient's condition continued to deteriorate and she sadly died. Conclusion(s): * The Early Warning Score significantly underestimated how unwell the patient was upon arrival in ED, a systems-based assessment would have demonstrated that the patient had multiple system dysfunction and significant potential to deteriorate suddenly despite having stable observations * The methotrexate level has no clinical value in diagnosing or refuting a diagnosis of methotrexate toxicity * A full examination of the immunosuppressed patient including ENT is a necessity when searching for a source of infection * Invasive fungal infections can cause multi-system symptoms and atypical presentations * As a greater proportion of patients have received systemic immunosuppression for Covid-19, vigilance for more unusual pathogens, including Mucormycosis by clinicians is advised.

A Case Report of Ivermectin-Induced Liver Failure

Introduction: Ivermectin is an antiparasitic medication that is primarily metabolized by the liver. During the COVID-19 pandemic, researchers demonstrated that Ivermectin successfully inhibited the replication of SARS-COV-2 in vivo, but current research has failed to demonstrate clinical benefit for treatment of COVID-19. Despite this, misinformation campaigns have misled patients to ingest Ivermectin at concentrations meant for domestic animals. Here, we present a case of acute liver failure secondary to the use of Ivermectin. Case Description/Methods: A 61-year-old man with medical history of ischemic cardiomyopathy with last echocardiogram showing ejection fraction at 21%, atrial fibrillation on warfarin for oral anticoagulation, and previously treated Hepatitis C presented with generalized weakness and yellowish discoloration of the skin worsening over the last two weeks. The patient denied significant alcohol use, acetaminophen use, or illicit drugs. He admitted to injecting himself with two doses of weight-based horse ivermectin, for COVID prophylaxis, two weeks prior to his presentation. Physical exam was pertinent for scleral icterus and hepatomegaly with no abdominal tenderness. Initial labs revealed elevated liver chemistries in a mixed pattern (Figure 1). Acute hepatitis panel, HSV, and CMV were negative. Hepatitis C antibodies were positive, but the patient was in sustained virologic response. Full workup for chronic liver disease was unremarkable. Ultrasound revealed hepatosplenomegaly with patent portal and hepatic vasculature. Subsequently, the patient developed hepatic encephalopathy along with his coagulopathy, raising concern for acute hepatic failure. The patient was transferred to the ICU and started on NAcetylcysteine, rifaximin, and supportive care. The patient recovered well and fortunately did not require liver transplant. Discussion(s): While the FDA recommends against the use of Ivermectin for COVID-19, many continue to inappropriately consume it. Ivermectin-induced liver failure is a rare but deadly side effect. Given our patient's rapid onset of symptoms post-self injection of Ivermectin, his liver injury was presumed to be related to Ivermectin. The drug interaction between Ivermectin and warfarin had worsened the patients coagulopathy. Physicians should be aware of the ways Ivermectin overdose may clinically present to avoid delayed treatment. This case demonstrates the detriments of perpetuation of medical misinformation to care.

Case report: Favipiravir-induced bluish corneal discoloration in infant with COVID-19.

This report describes a case of a male infant diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who was prescribed favipiravir therapy. The mother noticed a discoloration of the child's eyes within 18 h of therapy, and the cornea returned to normal color within 5 days of medication cessation. This case report highlights the need for monitoring of favipiravir therapy in children due to the potential side effect of corneal discoloration, which has not yet had its long-term effects identified.

Real world evidence from a Breast Screening pilot for the underprivileged: Experiences from Bruhat Bengaluru Mahanagara Palike hospitals

Background: In India, less than 5% of women get routine screening for breast cancer due to lack of awareness and the absence of a coordinated national breast cancer screening programme. A community health initiative was launched by Niramai in collaboration with City Health officials in Bangalore as a pilot to increase awareness and make breast health screening available to all. Free breast cancer screening using AI powered Thermalytix test is being offered to all the underprivileged women walking into Bruhat Bengaluru Mahanagara Palike (BBMP) government hospitals from November 14, 2017 till today (after a break for 15 months during COVID). Material(s) and Method(s): This observational study was conducted in 22 BBMP-affiliated primary health centers where outpatient women over the age of 18 years and not pregnant were enrolled. The procedure included a briefing on camp procedures, taking patient consent, identification of eligible candidates, general health education, and conducting the Thermalytix test by a healthcare worker who was trained to use the Thermalytix software tool. Women were triaged using the output generated by Thermalytix 180. Those triaged as red were referred for further detailed imaging investigation in a district hospital using mammography, ultrasound and FNAC/biopsy. Result(s): A total of 6935 women underwent Thermalytix screening in 22 BBMP hospitals during Nov 2017 to July 2022. A total of 1687 participants were excluded from the analysis as they did not meet the eligibility criteria. The median age of the 5248 eligible participants was 42 years (range 18-86). Among them, 90 women (1.71%) had previously noticed a lump in their breast, 431 women (8.12%) had breast pain, 16 women had complained of nipple discharge, and 5 women had noticed skin discoloration. When screened, 62 (1.2%) women were detected with abnormalities and triaged positive by Thermalytix. Among them 11 women have so far gone through diagnostic investigations, of which 8 were radiologically positive and were recommended for histopathology correlation. The overall test positivity rate of Thermalytix in this cohort was 1.2% and positive predictive value with radiological positivity as reference was found to be 9/11 = 81.81%. Furhter histological analysis reported 1 DCIS and 8 benign fibroadenoma. The tests were conducted in screening camps and the average cost of conducting the test in the field came to around 6.5 USD per person. Conclusion(s): Thermalytix could be a potential automated screening tool for population-level screening in resource constrained settings. The portable equipment enabled easy movement across different PHCs. Since it is a privacy-aware test, there was less refusal to participate in the test. Community mobilization with the help of the local government health officials was crucial to ensure walk-ins. Conflict of interest: Ownership: yes Board of Directors: yes Corporate-sponsored Research: yesCopyright © 2022 Elsevier Ltd. All rights reserved

Lesion Sterilization and Tissue Repair of Laterally Luxated Primary Mandibular Incisor: A Case Report

Lateral luxation injuries are common during childhood and in young adolescence. These injuries involve the surrounding tissues that could lead to extensive clinical treatment problems with a risk of pulpal complications such as pulp necrosis. A case of a healthy 4-year-old Malay boy visiting the paediatric dental clinic after seven months of laterally luxated injury on the lower right lateral incisor (tooth 82) was reported. The traumatic tooth was splinted by a private practitioner three days after the trauma, however, the splint dislodged less than 24-hour after placement. In view of the mother's fear of bringing her child to the dentist due to the COVID-19, no follow-up and further treatment were carried out. This has resulted in the development of discolouration and pulpal necrosis to the injured tooth. Lesion sterilization and tissue repair technique (LSTR) was performed. This report highlights the rare occurrence of lateral luxation injury on tooth 82 and the management of pulp necrosis as a complication via lesion sterilization and tissue repair technique due to the uncooperative behaviour of the child.Copyright © 2022, Faculty of Medicine, University of Malaya. All rights reserved.

Severe progression of autoimmune hepatitis in a young COVID-19 adult patient: A case report

Rationale: The impact of COVID-19 in patients with autoimmune liver disease treated with immunosuppressive therapy has not been described so far. This case report describes the clinical course of a patient with autoimmune hepatitis (AIH) who developed COVID-19 and the features of cytokine syndrome leading to its deterioration in our intensive care unit. Patient's Concern: A 28-year-old male presented with generalized anasarca for two weeks and chronic liver disease for 8 months. Diagnosis: AIH and Covid-19 with features of cytokine storm syndrome. Interventions: Intravenous furosemide, mannitol, syrup lactulose, steroids (prednisolone 40 mg), azathioprine 1 mg/kg body weight, rifaximin, vitamin K, and blood products. Outcomes: The patient had hepatic encephalopathy and AIH and died on the 10th day after admission despite ventilatory support, sustained low-efficiency hemodialysis, and resuscition. Lessons: The dramatic release of cytokines and the inflammatory-immune responses not only alter the pathophysiology but also affects the onset and severity of disease progression in patients with AIH.

Evaluation of the Degradation of Materials by Exposure to germicide UV-C Light through Colorimetry, Tensile Strength and Surface Microstructure Analyses

Due to the COVID19 pandemic, solutions to automate disinfection using UV-C combined with mobile robots are beginning to be explored. It has been proved that the use of these systems highly reduces the risk of contagion. However, its use in real applications is not being as rapid as it needs to be. One of the main market input barriers is the fear of degrading facilities. For this reason, it is crucial to perform a detailed study on the degradation effect of UV-C light on inert materials. This experimental study proves that, considering exposition times equivalent to several work years in hospital rooms, only the appearance of the material is affected, but not their mechanical functionalities. This relevant result could contribute to accelerate the deployment of these beneficial disinfection technologies. For that purpose, a colorimetry test, tensile strength test, and analysis of the surface microstructure were carried out. The results showed that polymers tend to turn yellow, while fabrics lose intensity depending on the color. Red is hardly affected by UV-C, but blue and green are. Thus, this study contributes to the identification of the best materials and colors to be used in rooms subjected to disinfection processes. In addition, it is shown how the surface microstructure of the materials is altered in most of the materials, but not the tensile strength of the fabrics.

Role of Physiotherapist in management of Covid-19 Patients: A Review

Corona virus disease also referred to as COVID-19 is a virulent infectious disease which is highly communicable. The WHO has confirmed the COVID-19 outburst as a pandemic. The main signs of the corona virus are fever, dry cough, tiredness, sputum production and shortness of breath whereas some patients also shows aches, pain, sore throat, Diarrhoea, conjunctivitis, Headache, loss of taste or smell, a rash on skin, or discolouration of fingers or toes, Physiotherapy plays a vital part of the treatment of COVID-19. The aim of this article is to highlight the importance and benefits of Physiotherapy interventions in the management of COVID 19 patients.

Safety and Tolerability of Sars-Cov-2 Vaccination and Natural History of Infection Among Patients with Castleman Disease

Castleman Disease (CD) represents a group of rare and heterogeneous hematologic disorders that have common lymph node histopathology. Patients with CD are often immunosuppressed as a consequence of immunemodulating therapy or possibly due to an underlying immunologic dysfunction attributable to B-cell dysfunction. The most severe CD cases experience a cytokine storm disorder, a life-threatening exacerbation of circulating cytokines and immune-cell hyperactivation. Infection with SARS-CoV-2 progresses to a severe cytokine storm in the most severe cases of COVID-19. Interleukin-6 (IL-6) is central to the pathogenesis of CD, and increased IL-6 often accompanies severe COVID-19 cases;inhibition of IL-6 with monoclonal antibodies has been shown to be effective therapy for both CD and severe COVID-19. We therefore sought to understand the impact of COVID-19 infection on the natural history of CD and also examined the safety and tolerability of COVID-19 vaccines in this vulnerable patient population. Patients enrolled in a longitudinal natural history study of CD (N=298) were invited to participate in a survey designed to characterize their experience with COVID-19 disease and vaccination. Surveys were emailed to all eligible patients, and reminders were sent up to 3 times. All data is self-reported;descriptive analyses are reported herein. Of the 298 patients who received a survey, 101 (33.9%) completed it. Sixty-nine (68%) had been tested for SARS-CoV-2 at least once, and 10 (14.5%) reported testing positive - including 6 UCD, 3 iMCD, and 1 HHV8+ MCD patients. The reported prevalence of SARS-CoV-2 infection in the US compares at 10.5%. Two of the 10 patients reported asymptomatic disease (both UCD), 7 reported mild disease (4 UCD, 1 iMCD, 1 HHV8+MCD), and 1 reported moderate disease requiring hospitalization but not a ventilator or intensive care (iMCD). This severity distribution suggests that these potentially immunocompromised patients experience a range of disease severity consistent with SARS-CoV-2 infection in the broader US population. The most commonly-reported symptoms included fevers/chills, headaches, and loss of taste or smell (N=7 each), as well as shortness of breath/difficulty breathing, muscle and body aches, and cough (N=5 each). Rarer symptoms were also noted among the iMCD patients, including discoloration of skin, lips, or nailbeds (N=1) and newfound confusion (N=2). Two of the 10 patients reported stopping siltuximab treatment during their COVID-19 diagnosis;both subsequently resumed treatment. No other treatment changes were reported. Of the 101 respondents, 87 (86%) had received at least 1 vaccine dose. Treatments, such as immunosuppressants and immunomodulators, were paused for 7 of these patients including, during the vaccination period;this was presumably done to increase the likelihood of a robust response to the vaccine. Fifty-one patients (59%) reported side effects to either dose 1 or 2. Side effects were generally mild, and none required hospitalization. Side effects were more commonly reported after dose 2, with the most common being arm pain (N=34), fatigue (N=30), and headache (N=26). Of those who reported not receiving the vaccine, 2 intend to receive it in the future, 5 reported being unsure about receiving it, and 7 do not intend to receive the vaccine. Common concerns include potential interaction with CD (N=9) and limited safety data (N=8). This study represents the first investigation into the experience of CD patients with SARS-CoV-2 testing, diagnosis, and vaccination. We did not observe a markedly increased inflammatory response to SARS-CoV-2 infection, and vaccination was well-tolerated. A limitation is self-selection survey bias;it is possible that those who chose to participate represent those who had a milder reaction in general. However, it is noteworthy that there were no reports of severe disease in this sample. The prevalence of confirmed SARS-CoV-2 infection in this cohort (14.5%) is marginally higher than reported in the US population (10.5%) but statistical comp risons were not performed given that this study does not provide a general epidemiological estimate. However, the distribution of symptoms and vaccine adverse effects in this sample were comparable to the general population. Though additional follow-up is planned for the future, these data are an important basis for understanding the interaction of SARS-CoV-2 and CD. Disclosures: Casper: EUSA Pharma: Consultancy. Fajgenbaum: Pfizer: Other: Study drug for clinical trial of sirolimus;N/A: Other: Holds pending provisional patents for ‘Methods of treating idiopathic multicentric Castleman disease with JAK1/2 inhibition’ and ‘Discovery and validation of a novel subgroup and therapeutic target in idiopathic multicentric Castleman disease’;EUSA Pharma: Research Funding. OffLabel Disclosure: Our makes reference to the following: “Interleukin-6 (IL-6) is central to the pathogenesis of CD, and increased IL-6 often accompanies severe COVID-19 cases;inhibition of IL-6 with monoclonal antibodies has been shown to be effective therapy for both CD and severe COVID-19.” Inhibition of IL-6 with monoclonal antibodies for use in COVID-19 is off-label.