Cutaneous Manifestations in Patients with SARS- CoV-2 Infections

While SARS-CoV-2 is known to cause pneumonia and acute respiratory distress syndrome (ARDS), many extrapulmonary manifesta- tions of COVID-19 have also been observed. Cutaneous manifestations including erythematous rash, urticaria, and chickenpox-like vesicles have been described in patients with SARS-CoV-2. Six patients, two men and four women, in the age group of 50 to 60 years old, hospitalized with SARS-CoV-2 infection confirmed with real-time polymerase chain reac- tion (real-time PCR) presented cutaneous manifestations. The rash was confluent, spotty, centrifugal, and non-itchy on the head and torso. It was not hemorrhagic, and no crust or blisters were observed. The results of laboratory tests were normal, and the rash disappeared on its own. Sev- eral cases of cutaneous manifestations have been reported in patients with SARS-CoV-2 infection. Further studies are needed in order to assess the skin lesions and determine their association with COVID-19

Cutaneous Manifestations in Patients with SARS- CoV-2 Infections

While SARS-CoV-2 is known to cause pneumonia and acute respiratory distress syndrome (ARDS), many extrapulmonary manifesta- tions of COVID-19 have also been observed. Cutaneous manifestations including erythematous rash, urticaria, and chickenpox-like vesicles have been described in patients with SARS-CoV-2. Six patients, two men and four women, in the age group of 50 to 60 years old, hospitalized with SARS-CoV-2 infection confirmed with real-time polymerase chain reac- tion (real-time PCR) presented cutaneous manifestations. The rash was confluent, spotty, centrifugal, and non-itchy on the head and torso. It was not hemorrhagic, and no crust or blisters were observed. The results of laboratory tests were normal, and the rash disappeared on its own. Sev- eral cases of cutaneous manifestations have been reported in patients with SARS-CoV-2 infection. Further studies are needed in order to assess the skin lesions and determine their association with COVID-19

Status and perspectives of hospital mortality in a public urban Hellenic hospital, based on a five-year review

<p>Abstract</p> <p>Background</p> <p>Analysis of hospital mortality helps to assess the standards of health-care delivery.</p> <p>Methods</p> <p>This is a retrospective cohort study evaluating the causes of deaths which occurred during the years 1995–1999 in a single hospital. The causes of death were classified according to the International Statistical Classification of Diseases (ICD-10).</p> <p>Results</p> <p>Of the 149,896 patients who were discharged the 5836 (3.4%) died. Males constituted 55% and females 45%. The median age was 75.1 years (1 day – 100 years).</p> <p>The seven most common ICD-10 chapters IX, II, IV, XI, XX, X, XIV included 92% of the total 5836 deaths.</p> <p>The most common contributors of non-neoplasmatic causes of death were cerebrovascular diseases (I60–I69) at 15.8%, ischemic heart disease (I20–I25) at 10.3%, cardiac failure (I50.0–I50.9) at 7.9%, diseases of the digestive system (K00–K93) at 6.7%, diabetes mellitus (E10–E14) at 6.6%, external causes of morbidity and mortality (V01–Y98) at 6.2%, renal failure (N17–N19) at 4.5%, influenza and pneumonia (J10–J18) at 4.1% and certain infectious and parasitic diseases (A00–B99) at 3.2%, accounting for 65.3% of the total 5836 deaths.</p> <p>Neoplasms (C00–D48) caused 17.7% (n = 1027) of the total 5836 deaths, with leading forms being the malignant neoplasms of bronchus and lung (C34) at 3.5% and the malignant neoplasms of large intestine (C18–21.2) at 1.5%. The highest death rates occurred in the intensive care unit (23.3%), general medicine (10.7%), cardiology (6.5%) and nephrology (5.5%).</p> <p>Key problems related to certification of death were identified. Nearly half of the deaths (49.3%: n = 2879) occurred by the completion of the third day, which indicates the time limits for investigation and treatment. On the other hand, 6% (n = 356) died between the 29^thand 262^nddays after admission.</p> <p>Inadequacies of the emergency care service, infection control, medical oncology, rehabilitation, chronic and terminal care facilities, as well as lack of regional targets for reducing mortality related to diabetes, recruitment of organ donors, provision for the aging population and lack of prevention programs were substantiated.</p> <p>Conclusion</p> <p>Several important issues were raised. Disease specific characteristics, as well as functional and infrastructural inadequacies were identified and provided evidence for defining priorities and strategies for improving the standards of care. Effective transformation can promise better prospects.</p

A new role for inflammatory peroxidases in breast cancer development and metastasis

Breast cancer is the leading cause of cancer mortality in women worldwide. Although we have made significant improvements in the detection and treatment of localized breast cancer with women surviving longer than ever before, patients with metastatic disease have a far worse prognosis. Metastasis is the leading cause of death in breast cancer patients with a 5-year survival of less than 30% and is currently without a cure. Thus, improvements in the development of new treatments will have profound impact on outcomes for these patients. Recent insight into the interactions of stromal cells and cancer cells within the breast tumour microenvironment, such as immune cells, fibroblasts, extracellular matrix (ECM) proteins, and vasculature, have revealed that the stroma plays a critical role in regulating a favourable environment for breast cancer initiation, progression and metastasis. Therefore, aspects of stromal biology are the key focus for future studies to improve patient outcome, by identifying new targets for therapy development. The role of the innate immune infiltrates in regulating cancer progression has been receiving considerable attention over recent years. Clinical studies indicate the extent of neutrophil and eosinophil accumulation within the developing tumour microenvironment is strongly correlated with a poor patient prognosis and survival. Having infiltrated the tumour, these inflammatory cells deposit myeloperoxidase (MPO) and eosinophil peroxidase (EPO) in abundance. These enzymes have mainly been studied in the context of providing oxidative defence against invading pathogenic microorganisms, and to-date the functional consequence of their heightened presence within the tumour microenvironment has long been unclear. The work in this thesis aims to provide a mechanistic link between inflammatory peroxidase enzymes MPO and EPO, influencing stromal cells within the tumour microenvironment leading to tumour development and metastasis. Using physiological relevant ranges of peroxidases this study revealed that peroxidases possess a well-conserved pro-fibrogenic capacity to stimulate the migration of fibroblastic cells and promote their ability to secrete collagenous proteins to generate a functional ECM using both in vitro and in vivo approaches. Structurally, the ECM generated upon peroxidase stimulation demonstrated highly linearized collagen fibers synonymous with tumour ECM that is highly conducive for cancer cell adhesion, and invasion. This suggests that peroxidase-mediated collagen biosynthesis by cancer-associated fibroblasts may play an important role in tumour progression. The stimulation of angiogenesis is considered to be one of the most important hallmarks of tumour progression. Data in this thesis demonstrates for the first time the proangiogenic capacity of both MPO and EPO to significantly enhance the in vitro proliferation, migration and capillary formation of human endothelial cells that are fundamental in the process of angiogenesis. The use of a murine model of angiogenesis confirmed the ability of these peroxidase enzymes to facilitate the generation of functional blood vessels in an in vivo model. These results suggest that MPO and EPO play a crucial role as drivers of angiogenesis, with the potential to support the vascularization of tumours and promote growth and metastasis. In addition, the pro-angiogenic and pro-fibrotic activity displayed by peroxidases was blocked using the peroxidase inhibitor 4-ABAH, indicating that the catalytic activity is essential for its activity. Using the orthotopic 4T1 mouse mammary carcinoma model, we demonstrated for the first time that delivery of MPO and EPO directly into developing tumours increased primary tumour burden and concomitant with enhanced lung metastases. Histological inspection confirmed that MPO and EPO stimulated an increase in endothelial cell recruitment, fibroblast activation and collagen deposition within these tumours. In conclusion, our findings demonstrate for the first time that the peroxidase enzymes MPO and EPO confer a broader range of action than previously thought and exhibit potent effects in the tumour milieu on matrix function, composition, angiogenesis, tumour invasion and metastasis. Importantly, these studies identify the use of peroxidase inhibitors that block the catalytic activity of the enzyme, as a potential novel therapeutic strategy for breast cancer prevention and therapy.Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, Adelaide Medical School, 2016

The Antiviral Effect of Nirmatrelvir/Ritonavir during COVID-19 Pandemic Real-World Data

Introduction: Vaccination against SARS-CoV-2 and the prevalence of Omicron variants have reduced the risk of the severe clinical progress of COVID-19. However, the risk of breakthrough infections has increased, and early administration of an effective antiviral treatment is significant in order to prevent the severe progression of COVID-19 in vulnerable patients with comorbidities. Patients and methods: Adults with confirmed SARS-CoV-2 infection were included in a matched-pair retrospective study based on age, gender, comorbidities and vaccination status. They were divided into two groups: group A (n = 200) consisted of outpatients at increased risk of severe clinical progress who were treated with nirmatrelvir/ritonavir and group B (n = 200) consisted of non-hospitalized patients who did not receive antiviral treatment. Demographic data, clinical outcome (death, intubation), days of hospitalization, time for recovery, adverse events and treatment compliance were reported. Results: The median age (75.24 ± 13.12 years in the study group and 76.91 ± 14.02 years in the comparison group) and the proportion of males (59% vs. 60.5%, respectively) were similar between the two groups. A total of 6.5% of patients in group A and 10.5% in group B were unvaccinated against SARS-CoV-2. Three patients from group A (1.5%) and one hundred eleven (55.5%) from group B required hospitalization. The duration of hospitalization (3 days vs. 10 days in group B, p p < 0.001) was shorter in the study group. A rebound of SARS-CoV-2 infection within 8–12 days after diagnosis was documented in 6.5% of patients in group A and 8% of patients in group B. Conclusion: Oral treatment with nirmatrelvir/ritonavir in high-risk non-hospitalized patients was safe and effective in preventing the severe clinical progress of COVID-19 pneumonia. Early administration of antiviral agents in vulnerable outpatients combined with a full vaccination scheme is significant in order to avoid hospitalization and severe clinical outcomes

The Impact of the COVID-19 Pandemic on Antimicrobial Resistance and Management of Bloodstream Infections

Introduction: The pressure of the COVID-19 pandemic on healthcare systems led to limited roles of infectious diseases services, increased rates of irrational use of antimicrobials, and incidence of infections by multidrug-resistant microorganisms. The aim of the present study is to evaluate the incidence of antimicrobial resistance and the management of bloodstream infections before and during the COVID-19 pandemic at the University General Hospital of Alexandroupolis (Greece). Materials and Methods: This is a retrospective study conducted from January 2018 to December 2022. Data were collected from the University Microbiology Laboratory per semester regarding the isolated strains of Gram-positive and -negative bacteria in blood cultures and respiratory samples in hospitalized patients in medical and surgical wards and in the intensive care unit (ICU). Additionally, bloodstream infections with requested infectious disease consultations were reported (n = 400), determining whether these were carried out via telephone contact or at the patient’s bedside. Demographic data, comorbidities, focus of infection, antimicrobial regimen, duration of treatment, length of hospitalization, and clinical outcome were analyzed. Results: A total of 4569 strains of Gram-positive and -negative bacteria were isolated. An increasing trend was reported compared to the pre-pandemic period in the incidence of resistant Gram-negative bacteria, particularly in ICUs. Prior antimicrobial use and the rate of hospital-acquired infections were increased significantly during the pandemic. In the pre-pandemic period 2018–2019, a total of 246 infectious disease consultations were carried out, while during the period 2020–2022, the number was 154, with the percentage of telephone consultations 15% and 76%, respectively. Detection of the source of infection and timely administration of appropriate antimicrobial agents were more frequently recorded before the pandemic, and 28-day mortality was significantly reduced in cases with bedside consultations. Conclusion: The empowering of infectious disease surveillance programs and committees, rational use of antimicrobials agents, and bedside infectious disease consultations are vital in order to reduce the impact of infections caused by multidrug-resistant strains