Aviptadil: Class Effect of a Synthetic Vasoactive Intestinal Peptide as a Treatment Option in Patients with COVID-19 with Severe Respiratory Failure

Despite dynamic drug and vaccine development processes to reduce the disease burden of COVID-19, the treatment options are still very limited. Vasoactive intestinal peptide (VIP) has a diversified physiological action with specific features of lung protection-related activities. VIP inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gene replication in human monocytes and the viral replication in Calu-3 cells, thus further reducing the generation of proinflammatory mediators. Aviptadil, a synthetic form of VIP, is the only pulmonary therapeutic agent to have been granted ‘fast track’ status by the U.S. Food and Drug Administration (FDA) and to be allowed into both Phase II and III clinical trials. Initial binding of Aviptadil with non-structural protein (nsp) 10 and nsp16, which may inhibit the 2’-O-methyltransferase activity of the SARS-CoV-2 nsp10 and nsp16 complex. Aviptadil has already proved to be an effective option in the treatment of severe respiratory failures due to sepsis and other related lung injuries. Interim analysis results of this drug used in respiratory failure caused by SARS-CoV-2 has evolved a new hope in regard to safety and efficacy. The final results from a recently completed trial, as well as all currently ongoing trials, will clarify the class effect of this drug in the treatment of COVID-19 in future days.

The PPE Pandemic: Sex-Related Discrepancies of N95 Mask Fit

During the COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2, healthcare professionals across the world have been at high risk of transmission because of their direct contact with infected patients. In October 2020, the International Council of Nurses (ICN) confirmed that 1,500 nurses had died from COVID-19 in 44 countries and estimated that healthcare worker COVID-19 fatalities worldwide could be more than 20,000. To ensure protection of healthcare personnel, properly fitting personal protective equipment (PPE) must be worn. In a ‘one size fits all’ world, the differences between the fit of PPE for men and women can have devastating consequences. An N95 respirator mask is a component of PPE outlined by the Centers for Disease Control and Prevention (CDC) for protection against COVID-19; however, N95 masks do not offer protection if they do not fit properly. Fit testing is performed to ensure an adequate seal of the mask on the wearer. A single-institution retrospective review was performed on fit testing results for male versus female wearers in an attempt to elucidate a difference in failure rates. Females failed at a significantly higher rate than their male counterparts (6.67% female, 2.72% male; p=0.001), and the reason reported was often due to being ‘small-boned’ (p<0.0001). Sex-related differences in proper PPE fit are not new; however, the COVID-19 pandemic has made the situation more acute, and sex-specific N95 mask designs must be developed quickly, as the pandemic shows little signs of abating.

Cutaneous Mucormycosis of the Interscapular Region in an Immunocompetent Patient

Mucormycosis is an invasive fungal infection caused by opportunistic fungi of the phylum Glomeromycotan, subphylum Mucormycotina, mainly affecting individuals with immunosuppression. Cutaneous mucormycosis is the third most common clinical form of the disease preceded by pulmonary and rhinocerebral mucormycosis. The usual factors predisposing to this infection are individuals who are immunocompromised with conditions like HIV, haematological malignancies, and diabetes mellitus, but a significant proportion of patients are immunocompetent. The agents of mucormycosis are abundantly present in nature and are transmitted to the skin by direct inoculation. It may be due to needle sticks, stings, and bites by animals, motor-vehicle accidents, natural disasters, and burn injuries. The clinical presentation is non-specific, but an indurated plaque that rapidly evolves to necrosis (eschar) is a common finding. The infection can invade locally, and also penetrate into the adjacent fat, muscle, fascia, and bone, or become disseminated. It is difficult to diagnose because of the non-specific presentation of mucormycosis. Biopsy and culture should be performed. Treatment consists of multidisciplinary management, including surgical debridement, use of antifungal drugs (amphotericin B and posaconazole), and reversal of underlying risk factors, when possible. Mortality rates are significant, ranging from 4% to 10% in localised mucormycosis infection, but are lower than the other forms of the disease. The authors present a case here of a 38-year-old immunocompetent male with cutaneous mucormycosis at the interscapular region.

Implications and Aspects of Lyme Neuroborreliosis

Lyme borreliosis or Lyme disease affects thousands of people globally each year, and, with nervous system involvement, this disease can lead to the development of Lyme neuroborreliosis (LNB). If not diagnosed and treated properly, LNB can lead to serious life-long health implications for affected patients. The clinical manifestations and treatment regimens are relatively well-studied, but much remains unknown about the disease’s pathogenesis and epidemiology. In this review, the authors elucidate the knowns and unknowns of LNB.

Disseminated Phaeohyphomycotic Lymphadenitis with Cladophialophora Species

Objective: This study describes a case of disseminated phaeohyphomycotic lymphadenitis in a young female with delayed diagnosis and good clinical response after appropriate treatment. Methods: A 32-year-old female presented with erythematous to violaceous papules with oozing discharge bilaterally in her inguinal region for a few months. History revealed tuberculous meningitis 4 years earlier treated with first line anti-tuberculous therapy for 18 months, and 2 years previously she developed pigmented discharging lymph nodes bilaterally in her axillae. The histopathology of the biopsy of the axillary nodes showed chronic granulomatous inflammation with multiple branching septate fungal hyphae. She received amphotericin B for 21 days but without improvement. Biopsy from the inguinal lesions was sent for histopathology and culture. Results: Histopathology of the biopsy material showed chronic granulomatous inflammatory process with multinucleate giant cells, epithelioid cells, histiocytes, and lymphocytes with multiple branching septate fungal hyphae. Gram stain revealed moderate septate hyphae with numerous pus cells. Culture on Sabouraud dextrose agar yielded velvety olive–black colonies in the fourth week. Microscopic slide examination of culture material was suggestive of Cladophialophora species. The patient was started on voriconazole, which was continued for 6 months, and showed clinical improvement. Conclusion: Incomplete investigation of infectious lesions may delay diagnosis. Furthermore, clinical presentations are greatly influenced by the immune status of the host. Both histopathological and microbiological assessments are equally important for making a conclusive diagnosis. Anti-fungal therapy may delay the growth of fungi that normally grow within a week; thus, a longer incubation time may be warranted for fungal smear-positive samples.

Gross, Histopathological, and Ultrastructural Features in Patients with COVID-19: A Literature Review

The coronavirus disease (COVID-19) outbreak has led to swift efforts to learn about its clinical course, prognostic markers, and complications. Consequently, there is a lot of scattered information available regarding severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) but its pathophysiology is still poorly understood. Gross and microscopic findings are very important for understanding any disease, including COVID-19. This literature review examines and summarises the biopsy, gross autopsy, and other histopathological findings that have been reported in various organs in COVID-19 patients to increase the understanding of the disease. Many histopathological findings in various organs were nonspecific, especially in the liver and brain, while others were particular to SARS-CoV-2. Therefore, further histopathological studies and autopsies are necessary to obtain consistent and reliable findings in those with COVID-19 to fully understand the pathogenesis of the disease and the impact it has on individual organs.

Male Sex May Be the Defining Factor in Predicting Susceptibility to and Severity of SARS-CoV-2 Infection: A Case Series

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the virus that causes the coronavirus disease (COVID-19). This paper will describe a series of three confirmed cases of COVID-19 and use patterns observed in these cases to discuss the association of this infection with male sex through different mechanisms linked to the X chromosome. The patients’ symptoms and diagnostic testing are reviewed, while also focussing on the illness status of their immediate family members. It is known that the X chromosome is linked to SARS-CoV-2 viral infectivity through the androgen receptor gene which is located on the X chromosome, and that angiotensin-converting enzyme 2 has an unconfirmed pattern of X-linked inheritance of its allelic variants, some of which are known to afford stronger binding affinity to SARS-CoV-2. However, there are no studies that investigate these factors in combination with each other and how this combination predicts disease outcome in males versus females, providing a more concrete explanation for the observed pattern that suggests this disease leads to poorer disease outcomes in males. Investigation of these factor combinations will allow for greater understanding of the epidemiology of this virus and the development of more accurate guidelines for the prevention, diagnosis, management, and prognosis of SARS-CoV-2 infection.

Impact of the COVID-19 Pandemic on Trauma and Orthopaedic Service in the Republic of Ireland

Background: The novel coronavirus disease-2019 (COVID-19) has been identified as the cause of a rapidly spreading respiratory illness that is thought to have originated from Wuhan, China in early December 2019. Since then, the free movement of people has decreased, which has thus reduced the number of trauma-related casualties. The Irish governments initiated strict social distancing measures in response to the COVID-19 pandemic in late March 2020. It remains challenging to quantify the impact this had on reducing the spread of the virus. The viral outbreak has led to significant changes in the lifestyle of Irish citizens. The aim of this study was to examine the impact of the pandemic on activity, related to emergencies in trauma and orthopaedics departments. Methods: Patients admitted to the Trauma and Orthopaedic Department at Cork University Hospital (CUH), Cork, Ireland and South Infirmary Victoria University Hospital (SIVUH), Cork, Ireland between the 1st of March and the 15th of April 2020 were documented and compared to the patient admissions from the same time period in 2019. Results: The total numbers of lower limb trauma cases dropped by 20.44% from 137 (females: 87; males: 50) to 109 (females: 74; male: 35), (p=0.72). Of note, there was a 30.00% reduction in the number of male cases (from 50 to 35; p<0.05), in comparison to the 14.94% reduction observed in the female population (from 87 to 74; p<0.05). The total number of upper limb trauma cases increased by 0.14% from 90 (female: 44; men: 46) to 94 (female: 54; male: 40; p=0.14). The increase reported was only applicable to the female population; the number of male cases of upper limb trauma slightly decreased from 46 to 40 (p<0.005). Conclusion: The COVID-19 crisis has led to a decrease in the total numbers of lower limb trauma surgeries but an increase in the number of upper limb fractures. The main reduction was amongst the male patients, while the number of female cases increased.

Indoor Microbiome and The Rising Asthma Prevalence

The prevalence of asthma has increased in the past few decades in most developed and developing countries. Large-scale, cross-sectional epidemiological studies have reported several factors associated with asthma prevalence and severity, including parental asthma, tobacco smoking, preterm delivery, virus infection, and air pollution. However, a puzzling problem is that the time trends in the prevalence of these risk factors cannot explain the rise in asthma. For example, the prevalence of smoking and clinical pneumonia have been decreasing globally in the past few decades. Recent progress in high-throughput sequencing technology has promoted the progress of microbiome research and established associations between human and indoor microbiomes, and many metabolic, cognitive, and immune diseases including asthma and allergies. In this review, the authors systematically summarise the current literature, standard practice, and analysis pipeline in the field of indoor microbiome and asthma. The strength and limitation of different analytical approaches are discussed, including the utilisation of relative and absolute abundance in the associated studies. The authors discuss new frameworks of integrated microbiome research from different ecological niches, functional profiling from multiomics data, and how these new insights can facilitate understanding of asthma mechanisms and even the development of new personalised treatment strategies for the rising asthma epidemic.

Urinary Tract Infection in Children: A Review of the Established Practice Guidelines

Urinary tract infection (UTI) is a significant cause of morbidity in children. Delayed treatment is associated with complications that may result in chronic kidney disease and, subsequently, end-stage kidney disease. Over the years, clinical practice guidelines have advanced to ensure the best global practices in treating the infection and preventing its progression to chronic kidney disease. The established practice guidelines address five main questions: 1) which children should have their urine tested; 2) how the sample should be obtained; 3) which radiological tests are recommended after a diagnosis of UTI; 4) how the infection should be treated; 5) and how affected children should be followed up. There is a substantial overlap in the recommendations of the American Academy of Pediatrics (AAP) guidelines and the UK’s National Institute for Health and Clinical Excellence (NICE) guidelines. Subtle differences, however, exist between the two established guidelines. An evidence-based paradigm shift of some traditional concepts about UTI in children has contributed to the revision and update of these guidelines. Further research is needed to clarify the role of host and genetic factors in renal scarring, as well as the diagnostic criteria for UTI. This narrative review aims to discuss the current recommendations of these established practice guidelines with an emphasis on the diagnosis, radiological investigation, treatment, and follow-up of UTI in children.