Dinah Parums

University of Oxford | OX · Pathology

Strains of avian influenza A, believed to have originated in poultry with transmission to wild birds, have been associated with epidemics and four major pandemics in humans in the past century. The 1918 influenza pandemic was caused by an avian strain of the influenza A(H1N1) virus that initially adapted to infect humans and then rapidly spread bet...

In November 2021, the World Health Organization (WHO) first identified the Omicron variant of SARS-CoV-2, B.1.1.529, as a variant of concern (VOC). By early 2022, the Omicron variant and its five lineages, BA.1, BA.2, BA.3, BA.4. and BA.5, had become the predominant cause of COVID-19 in most countries. The Omicron XBB.1.5 subvariant is a sublineage...

There is hope that 2023 could bring regulatory approval, licensing, and implementation programs for safe and effective adjuvanted vaccines to prevent malaria. Clinical trials involving the two leading adjuvanted malaria vaccines directed to the Plasmodium falciparum circumsporozoite protein (PfCSP) are ongoing. These vaccines are RTS,S/ASO1 (Mosqui...

The COVID-19 pandemic, climate change, increased resistance to antifungal drugs, and an increased number of immunocompromised patients have driven a recent global surge in pathogenic fungal infections, including aspergillosis, candidiasis, and mucormycosis. On 25 October 2022, the World Health Organization (WHO) released a list of 19 fungal priorit...

In the past two decades, there have been rapid advances in the number and range of regulatory approvals of targeted therapy for patients with advanced non-small cell lung cancer (NSCLC) and other cancers. The Kirsten rat sarcoma viral oncogene homolog (KRAS) gene has a high mutation rate in human cancers and is associated with some of the most aggr...

One of the most recently described clinical associations with SARS-CoV-2 infection is rebound COVID-19, which occurs between five and eight days following the cessation of antiviral treatment. Most case reports of rebound COVID-19 have been associated with cessation of treatment with the combined oral antiviral agent nirmatrelvir/ritonavir (Paxlovi...

Monkeypox is caused by an orthopoxvirus, which is a DNA virus. Monkeypox is a zoonotic viral infection that has been endemic in West Africa and Central Africa for over a decade. Between 1 January and 22 June 2022, the World Health Organization (WHO) reported 3,413 laboratory-confirmed cases of monkeypox from 50 countries. Most cases (86%) were repo...

Monkeypox is caused by an orthopoxvirus, which is a DNA virus. Monkeypox is a zoonotic viral infection that has been endemic in West Africa and Central Africa for over a decade. Between 1 January and 22 June 2022, the World Health Organization (WHO) reported 3,413 laboratory-confirmed cases of monkeypox from 50 countries. Most cases (86%) were repo...

The range of long-term clinical conditions following SARS-CoV-2 infection in adults is now recognized. However, the prevalence, presentation, and risk factors for long COVID, or post–COVID-19, in children are less well understood because there have been few follow-up studies or long-term clinical trials in children with COVID-19. However, recent st...

On 26 November 2021, the World Health Organization (WHO) identified the B.1.1.529 variant, or Omicron variant, as the fifth variant of concern (VOC) of SARS-CoV-2. The B.1.1.529 Omicron variant of SARS-CoV-2 includes five lineages, BA.1, BA.2, BA.3, BA.4. and BA.5. During the past six months, several identified sublineages of B.1.1.529 have rapidly...

The consequences of SARS-CoV-2 infection include short-term, long-term, mild, and severe clinical symptoms. The cardiovascular system, including endothelial cells, vascular smooth muscle cells, and cardiac myocytes, are important targets for SARS-CoV-2. In February 2022, the findings from a large US cohort of individuals diagnosed with COVID-19 and...

The Nuvaxovid™ (NVX-CoV2373) Novavax vaccine is a recombinant spike (S) protein nanoparticle vaccine combined with the Matrix-M adjuvant. On December 20, 2021, the European Commission of the European Union (EU) granted conditional marketing authorization for the Nuvaxovid™ (NVX-CoV2373) Novavax vaccine, following recommendations from the European M...

The omicron variant of SARS-CoV-2, B.1.1.529, was included in the World Health Organization (WHO) list of variants of concerns (VOC) on 26 November 2021. Within only three months, omicron has spread rapidly to become the dominant variant in many countries. Studies have begun to evaluate the virulence, transmissibility, and degree of immune protecti...

On 4th November 2021, the first oral antiviral drug for COVID-19, molnupiravir (Lagevrio®), received full regulatory approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK. Molnupiravir is an orally bioavailable antiviral drug for use at home when a SARS-CoV-2 test is positive. On 22 nd December 2022, the FDA granted...

In 2021, data from global disease monitoring and infection surveillance programs have shown that vaccination programs have reduced the incidence of SARS-CoV-2 infection and hospitalization and mortality rates. Currently, the US Centers for Disease Control and Prevention (CDC) identifies a fully vaccinated individual as being ³14 days after the comp...

Healthcare professionals have an ethical, medico-legal, and professional responsibility to report all suspected adverse events following immunization to relevant national reporting agencies as part of the process of post-marketing drug safety monitoring. In the US, the Vaccine Adverse Event Reporting System (VAERS) is co-sponsored by the Centers fo...

Some of the most challenging guidelines for clinical practice include recommendations for disease prevention , which often involve lifestyle modifications, which may vary between populations. On August 30, 2021, the European Society of Cardiology (ESC) published new guidelines for primary and secondary prevention of atherosclerotic cardiovascular d...

The development and use of digital health technology have increased during the global COVID-19 pandemic. Artificial intelligence (AI)-powered digital tools have been increasingly used to diagnose and screen for SARS-CoV-2 infection. Digital technology, in the form of mobile phone applications (apps), has been adopted by several countries to track i...

Recent studies on the pathogenesis and clinical spectrum of human disease following infection with the new human pathogen, SARS-CoV-2, have identified the varied presentations and sequelae of COVID-19. Acute 'cytokine storm' in severe COVID-19 results in multiorgan damage due to vascular hyperpermeability, edema, and hypercoagulation. The long-term...

There have been five viral pandemics in the past century, four were due to influenza, and the ongoing COVID-19 pandemic is due to SARS-CoV-2 infection. During the COVID-19 pandemic, there has been a 99% global reduction in the diagnosis of influenza. Also, from 2020, global mortality rates from influenza fell to record levels during the influenza s...

The coronavirus disease 2019 (COVID-19) pandemic has affected the number of completed clinical trials, particularly in oncology. Between 80-85% of all lung cancers are non-small cell lung cancer (NSCLC), and of these, between 2-3% have an EGFR exon 20 insertion, which is associated with increased cell proliferation, metas-tasis, and a lack of respo...

During the past two years, clinical studies have attempted to identify risk factors to predict clinical outcomes following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In July 2021, a study using a high-throughput technique detected autoantibodies to chemokines, cytokines, and complement components in patients with s...

Malaria affects more than 3 billion people in 95 countries, with an estimated mortality rate of 400,000 per year. The female Anopheles spp mosquito most commonly transmits malaria, and the main burden of disease is due to Plasmodium falciparum. The most abundant antigen on the sporozoite surface is the Plasmodium fal-ciparum circumsporozoite protei...

In the past 18 months, accelerated vaccine development to prevent or reduce the severity of coronavirus disease 2019 (COVID-19) has resulted in rapid global emergency regulatory approvals, including the US Food and Drug Administration (FDA) emergency use authorization (EUA) approvals. On August 23, 2021, the US FDA gave the first full regulatory ap...

During 2020 and 2021, the COVID-19 pandemic has resulted in interruptions and cancellations of clinical trials and has delayed drug development in all areas except SARS-CoV-2 vaccine development. A further concern is the need to rapidly share anonymized datasets and improve opportunities to conduct randomized clinical trials (RCTs) in low-resource...

Subjective narrative review articles have an educational and informative role in medical and scientific journals. Systematic review of the literature requires an objective and complete review of all available publications on an identified topic. Systematic review that undergoes meta-analysis aims to provide a complete and objective evaluation of al...

Regulatory authorities, including the US Food and Drug Administration (FDA), have accelerated diagnostic and therapeutic approvals during the coronavirus disease 2019 (COVID-19) pandemic. Accelerated clinical development and approvals have resulted in vaccine programs for severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2). However, some...

The World Health Organization (WHO) estimated that in 2019, 10.0 million people worldwide developed tuberculosis (TB), with 1.4 million deaths from TB in that year. Infection with Mycobacterium tuberculosis that is resistant to at least isoniazid and rifampin and an additional chemotherapeutic agent is known as multidrug-resistant TB (MDR TB). Unti...

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) commonly presents with pneumonia. However, COVID-19 is now recognized to involve multiple organ systems with varying severity and duration. In July 2021, the findings from a retrospective population study from the National COV...

Current treatments for patients with Alzheimer's disease aim to improve behavioral, cognitive, and non-cog-nitive symptoms. There have been no new drug approvals for preventing or treating Alzheimer's disease for more than two decades. Drug development in Alzheimer's disease aims to identify disease-modifying therapies that will delay or slow the c...

This manuscript has been retracted at the author's request due to possible conflict of interest.Reference:Dinah V. Parums. Editorial: mRNA Vaccines and Immunotherapy in Oncology: A New Era for Personalized Medicine. Med Sci Monit 2021;27:e933088. DOI: 10.12659/MSM.933088.

Vaccinated, non-vaccinated, and immunosuppressed individuals will continue to be infected with SARS-CoV-2. Therefore, there is a priority to develop treatments that reduce the severity of COVID-19 in patients who require hospital admission. Interleukin-6 (IL-6) is a proinflammatory cytokine. In 2011, a humanized monoclonal antibody to the IL-6 rece...

During the global COVID-19 pandemic, data from clinical studies, systematic review, and population registry data have shown that when compared with non-pregnant women, SARS-CoV-2 infection in pregnancy is associated with a small increase in risk to the mother. Large cohort studies and registry data collected from 2020 have included the US Surveilla...

Artificial intelligence (AI) in clinical medicine includes physical robotics and devices and virtual AI and machine learning. Concerns have been raised regarding ethical issues for the use of AI in surgery, including guidance for surgical decisions, patient confidentiality, and the need for support from controlled clinical trials to use these metho...

The global pandemic of coronavirus disease 2019 (COVID-19) has identified thousands of genome sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). On 31st May 2021, the Virus Evolution Working Group of the World Health Organization (WHO) announced its recommendations for revised naming of SARS-CoV-2 variants of concern (VOCs)...

Patient registries include data on patient diagnosis, demographics, treatment, and outcomes and are now fundamental to the provision of successful global health systems. Patient registries include mainly local, regional, and national patient data on general or specific patient groups. Global registries currently exist mainly for rare diseases. Some...

During 2020, increasing numbers of case reports, case series, and small observational studies reported long-term complications of coronavirus disease 2019 (COVID-19) in patients who had recovered from acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Long COVID has a prevalence of between 10-30% in patients with a r...

In early 2020, at the beginning of the coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare cases were reported in children and adolescents of multisystem inflammatory syndrome in children (MIS-C). MIS-C is characterized by fever, systemic inflammation, and multiorgan dysfunction and...

During the past four decades, the identification of phenotypic changes in malignant tumor cells has been refined by the standardization of immunohistochemistry methods. Regulatory-approved companion diagnostics were initially developed for immunohistochemistry and to support early tumor tissue-based clinical trials. In the last decade, molecular pr...

Synthetic mRNA and the expression of therapeutic proteins have accelerated vaccine development to prevent infection and heralds a new era in targeted immunotherapy in oncology. Therapeutic mRNA vaccines rely on available tumor tissue for gene sequencing analysis to compare the patient's normal cellular DNA sequences and those of the tumor. Carrier-...

There have been rapid developments in safe and effective mRNA vaccines for zoonotic infections in the past year. Years of research have made these advances possible, leading to in vitro-transcribed (IVT) mRNA expressing therapeutic proteins. There are several advantages of mRNA vaccines that include their low-cost manufacturing process, large-scale...

During 2020 and 2021, the global pandemic of coronavirus disease 2019 (COVID-19) due to severe acute respi- ratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in high death rates and acute and chronic morbidity in all countries. The rapid development of new mRNA vaccines to SARS-CoV-2 brings hope that the spread of this virus can be controlled...

Tumor tissue biomarkers are the basis for targeted therapy in non-small cell lung cancer (NSCLC). These biomarkers either reflect the target of the specific drug or some factor that might abrogate the effect of the drug. These targeted drugs are small-molecule inhibitors of a specific tyrosine kinase or a monoclonal antibody against a specific rece...

In this review on current therapy in non-small cell lung cancer (NSCLC), the current status of immune therapy is presented. This therapeutic area is dominated by the biological therapeutics, or "biologics". Firstly, the immune checkpoint inhibitors include antibodies to PD-1, e.g., nivolumab (BMS-936558) and pembrolizumab (MK-3475), and antibodies...

Tumor tissue biomarkers are the basis for targeted therapy in non-small cell lung cancer (NSCLC). These biomarkers either reflect the target of the specific drug or some factor that might abrogate the effect of the drug. These targeted drugs are small-molecule inhibitors of a specific tyrosine kinase or a monoclonal antibody against a specific rece...

To identify clinical and biometric features associated with overall survival of patients with advanced refractory non-small-cell lung cancer (NSCLC) treated with gefitinib. One hundred and nine diagnostic NSCLC samples were analysed for EGFR mutation status, EGFR immunohistochemistry, histologic morphometry and quantitative immunofluorescence of 15...

The ISEL (Iressa Survival Evaluation in Lung Cancer) clinical trial evaluated the efficacy of gefitinib versus placebo in pretreated nonsmall-cell lung cancer patients. Two different antibodies, scoring systems, and cutoff points of epidermal growth factor receptor (EGFR) protein expression were compared to predict response and survival of enrolled...

18065 Background: The abundant expression of the epidermal growth factor receptor (EGFR) in a variety of solid tumors including non-small cell lung cancer (NSCLC), head and neck, breast, colon and brain has made it an attractive target for various selective molecular therapeutics, including the tyrosine kinase inhibitor gefitinib. The recent eviden...

The phase III Iressa Survival Evaluation in Lung Cancer (ISEL) trial compared gefitinib with placebo in 1,692 patients with refractory advanced non-small-cell lung cancer. We analyzed ISEL tumor biopsy samples to examine relationships between biomarkers and clinical outcome after gefitinib treatment in a placebo-controlled setting. Biomarkers inclu...

Because angiogenesis and inflammation are intimately associated and endoglin is required for angiogenesis, we wished to determine whether it also plays a role in inflammation. Using an immunohistochemical approach, we examined spatial and temporal changes in endoglin expression during inflammation and angiogenesis. We found low levels of endoglin e...

To examine the effect of up to 6 weeks of corticosteroid treatment on the positive temporal artery biopsy rate in giant cell arteritis (GCA). Prospective comparative clinical study of 11 patients meeting the American College of Rheumatology criteria for diagnosis of GCA. Patients underwent temporal artery biopsy within 1 week, at 2-3 weeks, or afte...

J Thorac Cardiovasc Surg 2002;123:817-20

We describe a case of donor-acquired small cell lung cancer after pulmonary transplantation for cystic fibrosis. The recipient was an ex-smoker with minimal smoking history and had been abstinent for 20 years. At the time of death, the donor chest radiographic finding was normal. The recipient had multiple posttransplant bronchoscopies and a normal...

In patients with postischaemic left ventricular dysfunction, segments recovering function after revascularisation (hibernating myocardium) may not respond during dobutamine echocardiography, despite preserved [(18)F] 2-fluoro-2-deoxy-D-glucose (FDG) uptake at positron emission tomography. To investigate whether this lack of response might reflect t...

Endoglin (CD105) is expressed on the surface of endothelial and haematopoietic cells in mammals and binds TGFbeta isoforms 1 and 3 in combination with the signaling complex of TGFbeta receptors types I and II. Endoglin expression increases during angiogenesis, wound healing, and inflammation, all of which are associated with TGFbeta signaling and a...

Coagulation is triggered during the onset of myocardial infarction, resulting in vascular occlusion. However, a causal role for individual haemostatic factors in the development of thrombotic occlusion is not established. Three cases (all relatively young women) are reported of raised factor VIII associated with myocardial infarction. Two patients...

Pulmonary Langerhans’ cell granulomatosis (LCG) is a diffuse, smoking-related lung disease characterised pathologically by bronchiolocentric inflammation, cyst formation, and widespread vascular abnormalities, and physiologically by exercise limitation. Pulmonary fibrosis is a long term sequel. Diagnosis may be made by lung biopsy and by bronchoalv...

Lord Hunt of Everest presented with aortic stenosis but predominant right ventricular failure. He was found to have signs of pulmonary hypertension with a dilated right ventricle, severe tricuspid regurgitation, and right atrial hypertrophy in the absence of elevated pulmonary artery pressures. He is a lifelong mountaineer and we attribute these fi...

The aim of this study was to provide evidence for the hypothesis that the B cell rich infiltrate concentrated in the adventitia of atherosclerotic abdominal aortic aneurysms is an autoimmune response to specific tissue antigens. Detailed histological examination of biopsies from 26 atherosclerotic abdominal aortic aneurysms showed in the adventitia...

Editor—In their editorial on amiodarone pulmonary toxicity Gillian A J Jessurun and Harry J G M Crijns made several misleading statements about the diagnosis of this dangerous condition.1 Although they are correct in stating that pulmonary toxicity has rarely been reported after low doses of amiodarone or after short periods of treatment, they make...

It is very easy to reassure patients with soft painless swellings on the sole of their foot that they have a lesion of no importance. We present a case report in which modern imaging techniques with magnetic resonance iamging and digital subtraction angiography prompted a diagnosis of malignancy and made excision biopsy mandatory.

Inflammatory cytokines associated with atherosclerosis may be capable of stimulating the synthesis and activity of inducible nitric oxide synthase (iNOS), which could further influence the pathologic features associated with the disease. Although there is a certain amount of indirect evidence to support the presence of iNOS in atherosclerosis, ther...

Myxomas are one of the most common cardiac tumors but usually are confined to the atria. Although described in all cardiac chambers and on all cardiac valves, only one postmortem case of an aortic valve myxoma has been published. We present the case of a young man with an aortic valve myxoma with peripheral embolization. The other pathologic condit...

Atherosclerosis is accompanied by lipid accumulation, cellular proliferation and intimai inflammation. T lymphocytes and macrophages, many of which are activated, are present in the fatty streak, the fibrofatty plaque and the complicated or advanced plaque, and have therefore been implicated in atherogenesis.1–5

To determine whether aortic adventitial chronic inflammation associated with advanced atherosclerosis ("chronic periaortitis") is associated with any detectable cytokine gene expression. RNA was extracted from six fresh surgical specimens of atherosclertic aortic aneurysm wall showing a spectrum of chronic periaortitis. Controls included four norma...

This article reviews the histopathological, clinical and immunological features of the arteritides. Based on these criteria, a classification scheme is proposed that includes infectious and non-infectious causes. Included in the non-infectious arteritides are: hypersensitivity vasculitis including serum sickness. Henoch-Schönlein purpura, mixed cry...

Chronic periaortitis is a local complication of human atherosclerosis. It is defined as the triad of advanced atherosclerosis, medical thinning and aortic adventitial chronic inflammation. It is present to a variable degree in association with atherosclerotic abdominal aortic aneurysms. These aortic adventitial infiltrates differ from those describ...

A dual-labeling technique was developed for direct quantification of specific mRNA using a flatbed liquid scintillation counter. This method simultaneously measures cpm of 32P- and 35S-labeled probes bound to RNA dot blots and subtracts counts due to nonspecific background radioactivity bound to the filter. Probes for T-cell receptor and beta-actin...

Chronic inflammatory cells are a recognized component of atherosclerotic plaques at all stages of development. As adhesion molecules play a fundamental role in inflammatory processes, we have carried out an immunohistochemical investigation of the distribution of endothelial leucocyte adhesion molecule-1 (ELAM-1)*, intercellular adhesion molecule-1...

To determine the phenotype of proliferating cell populations. The double immunostaining technique combines the autofluorescent properties of alkaline phosphatase substrate naphthol/Fast Red with immunofluorescence using fluorescein. Fresh human tonsil and fresh atherosclerotic aortic aneurysm wall tissue were studied using a panel of monoclonal ant...

An apparently immunocompetent 78 year old woman presented with confusion, subcutaneous abscesses, and lesions of the nasopharynx. Gram positive, acid fast bacilli were isolated from her blood after 10 days' incubation. She was treated with trimethoprim-sulphamethoxazole for presumed disseminated nocardiasis but deteriorated and died. A post mortem...

Donor homograft vein is sometimes used in vascular surgery when autograft vein is not available. The optimum mode of storage remains controversial. An ideal solution would cause cellular disruption and thus decrease the immunogenicity of the donor vein, and allow a preserved collagen matrix and basement membrane, required to maintain the structure....

During ureterolysis in a patient with "idiopathic retroperitoneal fibrosis", fresh samples of peri-ureteric and peri-aortic tissue were obtained. An abdominal CT scan confirmed the peri-aortic distribution of the inflammation associated with advanced abdominal aortic atherosclerosis. Histology confirmed the presence of fibrosis and a variable chron...

During repair of 12 atherosclerotic abdominal aortic aneurysms, fresh samples of aneurysm wall were obtained. Histology confirmed the presence of advanced atherosclerosis associated with medial thinning and a variable aortic adventitial chronic inflammatory cell infiltrate. Monoclonal antibodies were used to identify the inflammatory cells througho...

A new monoclonal antibody, JC70, raised against a membrane preparation from a spleen affected by hairy cell leukaemia, recognises a membrane bound glycoprotein identical with that of the CD31 group of monoclonal antibodies. The antibody stains a fixation resistant epitope on endothelial cells in benign and malignant conditions in a wide variety of...

A review of the histology of 440 sections of atherosclerotic aortas and arteries showed that 85% contained advanced atherosclerotic plaques. Of these, 92% showed some degree of adventitial inflammation with subclinical chronic periaortitis in 49%. A review of 20 cases of clinical chronic periaortitis, which included 12 cases of inflammatory aneurys...

The extent of tumour growth beyond the muscularis propria (mesorectal spread) was measured in specimens from 167 consecutive patients with rectal cancer. The 5-year survival was significantly greater in patients with slight mesorectal spread (4 mm or less) than in those with more extensive mesorectal spread (55% [95% confidence interval 42-66%] vs...

The incidence of serum antibodies to human low-density lipoprotein, to oxidized low-density lipoprotein, and to ceroid extracted from human atheroma was assessed in 100 subjects using an adaptation of the enzyme-linked immunosorbent assay technique. Patients with chronic periaortitis, subclinical chronic periaortitis, and ischemic heart disease, an...