Editorial: Reasons for Increasing Global Concerns for the Spread of Mpox.

On August 14, 2024, the Director General of the World Health Organization (WHO) declared that the increasing outbreaks of mpox (formerly monkeypox) should be regarded as an international public health emergency due to the growing number of cases in endemic and non-endemic geographical areas, and increasing disease severity. The latest update from the WHO and the alerts given regarding the status of mpox follows an upsurge in the incidence and severity of mpox in the Democratic Republic of the Congo (DRC) and an increasing number of African countries, with spread to other continents and countries This Editorial aims to provide an update on the current status of mpox and includes reasons for the increasing global concerns for the spread of the mpox virus (MPXV).

Long COVID or Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) and the Urgent Need to Identify Diagnostic Biomarkers and Risk Factors.

Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), also known as post-COVID-19 condition or post-COVID syndrome, can affect anyone infected with SARS-CoV-2, regardless of age or the severity of the initial symptoms of COVID-19. Long COVID/PASC is the continuation or development of new symptoms after three months from the initial SARS-CoV-2 infection, which lasts for at least two months and has no other identifiable cause. Long COVID/PASC occurs in 10-20% of patients infected with SARS-CoV-2. The most common symptoms include fatigue, cognitive impairment (brain fog), and shortness of breath. However, more than 200 symptoms have been reported. No phenotypic or diagnostic biomarkers have been identified for developing long COVID/PASC, which is a multisystem disorder that can present with isolated or combined respiratory, hematological, immunological, cardiovascular, and neuropsychiatric symptoms. There is no cure. Therefore, individualized patient management requires a multidisciplinary clinical approach. Because millions of people have had and continue to have COVID-19, even in the era of vaccination and antiviral therapies, long COVID/PASC is now and will increasingly become a health and economic burden that the world must prepare for. Almost five years from the beginning of the COVID-19 pandemic, this article aims to review what is currently known about long COVID/PASC, the anticipated increasing global health burden, and why there is still an urgent need to identify diagnostic biomarkers and risk factors to improve prevention and treatment.

Editorial: Genome Editing Goes Beyond CRISPR with the Emergence of 'Bridge' RNA Editing.

Therapeutic human gene editing technologies continue to advance, with the endonuclease, clustered regularly interspaced short palindromic repeats (CRISPR) being one of the most rapidly developing technologies. Recently, in 2024, a method of RNA editing called 'bridge editing' has been described in bacteria, which is more powerful and has broader applications than CRISPR to reshape the genome. The term 'bridge editing' is used because the method physically links, or bridges, two sections of DNA and can alter large sections of a genome. 'Bridge editing' relies on insertion sequence (IS) elements, the simplest autonomous transposable elements in prokaryotic genomes. This method provides a unified mechanism for the three fundamental types of DNA rearrangement required for genome design: inversion, insertion, and excision. The 'bridge' recombination system could expand the range and diversity of nucleic acid-guided therapeutic systems beyond RNA interference and CRISPR. This editorial aims to introduce new developments in 'bridge' RNA editing that have the increased potential to reshape the genome.

A Review of the Increasing Global Impact of Climate Change on Human Health and Approaches to Medical Preparedness.

At the end of 2023, the World Health Organization (WHO) identified climate change as the greatest threat to human health. Global climate change is due to rising atmospheric concentrations of greenhouse gasses, primarily due to the burning of fossil fuels, mainly by populations in developed and developing countries. In 2022, the world experienced the highest temperatures for over 100,000 years. However, in 2022, global investment in fossil fuels increased by 10% and reached more than USD 1 trillion. The 2023 Lancet Commission report concluded that there has been little progress in protecting individuals from the adverse health effects of climate change. It is clear that global action against climate change needs to move more quickly, and the inequalities in the effects of climate change, including the impact on health, are increasing. This article aims to review the ongoing global impact of climate change on human health at individual and population levels, including recent initiatives and medical approaches to prepare for this increasing challenge.

Editorial: The Global Threats of Increasing Antimicrobial Resistance Require New Approaches to Drug Development, Including Molecular Antimicrobial Adjuvants.

Antimicrobial resistance and the associated morbidity and mortality from untreatable common infectious organisms is an increasing threat to global public health. In 2019, the Antimicrobial Resistance Collaborators identified that antimicrobial resistance was directly responsible for up to 1.27 million deaths worldwide and was associated with up to 4.95 million deaths, with low-income and middle-income countries being the most severely affected. In 2019, before the COVID-19 pandemic began, they predicted that antimicrobial resistance could result in 10 million deaths per year by 2050, overtaking cancer as a leading cause of death worldwide. Therefore, there is an urgent need for new approaches to antimicrobial treatment. In June 2024, the findings from researchers at the Ineos Oxford Institute for Antimicrobial Research (IOI) and the Oxford University Department of Pharmacology in the UK reported the use of a small molecule that can work alongside antibiotics to suppress the development of antimicrobial resistance in bacteria. The SOS inhibitor molecule has been called OXF-077. This editorial aims to highlight the global threats from increasing antimicrobial resistance and the urgent need for new molecules that function through novel mechanisms of action, including molecular antimicrobial adjuvants.

Editorial: Concerns as Highly Pathogenic Avian Influenza (HPAI) Virus of the H5N1 Subtype is Identified in Dairy Cows and Other Mammals.

Highly pathogenic avian influenza (HPAI) virus subtypes have been increasingly identified in poultry and wild birds since 2021. Between 2020-2023, 26 countries have reported that the H5N1 virus had infected more than 48 mammalian species. On 1 April 2024, a public health alert was issued in Texas when the first confirmed case of human infection with the H5N1 influenza virus was reported in a dairy worker. Cases of H5N1, clade 2.3.4.4b in dairy cows have been reported in several states in the US but were unexpected, even though H5N1 was previously identified in mammalian species, including cats, dogs, bears, foxes, tigers, coyotes, goats, and seals. On 29 April 2024, almost one month after the first reported cases of H5N1 infection in dairy cows, measures were to be implemented by the US Department of Agriculture (USDA) to prevent the progression of H5N1 viral transmission. This editorial summarizes what is currently known about the epidemiology, transmission, and surveillance of the HPAI virus of the H5N1 subtype in birds, mammals, and dairy cows, and why there are concerns regarding transmission to humans.

A Review of the Current Status of Disease-Modifying Therapies and Prevention of Alzheimer's Disease.

Alzheimer's disease is the most common form of dementia and includes cognitive, personality, and behavioral changes. The 2024 report from the Alzheimer's Association estimated that 6.9 million adults >65 years in the US are currently living with Alzheimer's disease. Modeling studies predict that this number will double by 2050, and associated healthcare costs will reach $1 trillion. In June 2021, regulatory approval of aducanumab, a humanized recombinant monoclonal antibody to amyloid ß, initially raised expectations for improved disease-modifying therapy. However, in February 2024, production of aducanumab and a post-marketing clinical trial ceased in the US due to the costs and limitations of aducanumab therapy. In March 2024, biobank data identified significant modifiable risk factors for Alzheimer's disease, including diabetes mellitus, exposure to nitrogen dioxide (a proxy for air pollution), and the frequency of alcohol intake. Therefore, modification of identifiable risk factors, combined with testing for disease-susceptibility genes, could be the most effective approach to reduce the incidence. This article aims to review the current status of disease-modifying therapies and prevention of Alzheimer's disease.

Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) - Lifileucel (Amtagvi).

On February 16, 2024, the US Food and Drug Agency (FDA) granted accelerated approval to lifileucel (Amtagvi), an adoptive immune cell therapy with autologous ex vivo-expanded tumor-infiltrating lymphocytes (TILs) for adult patients with advanced or unresectable melanoma progressing after treatment with immune checkpoint inhibitors and, if BRAF V600 mutation-positive, BRAF/MEK inhibitors. The clinical studies supporting this regulatory approval have highlighted the complexity of the treatment manufacturing process and the requirements for patient selection, a pretreatment lymphodepletion regimen, followed by a single infusion of lifileucel (Amtagvi), and up to six treatments with high-dose IL-2, with the potential for adverse events at each stage of treatment. In early 2024, expert consensus guidelines were published on best practices and patient management for adoptive cell therapy with autologous, ex vivo-expanded TILs, and an international TIL Working Group was formed in anticipation of further regulatory approvals bringing these treatments to the clinic. This editorial aims to provide an update on the importance of a first approval for adoptive cell therapy with autologous, ex vivo-expanded TILs and the challenges of implementing a complex, time-consuming, and potentially costly immunotherapy.

Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection - Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug Resistance.

In April 1984, 40 years ago, the Secretary of the US Department of Health and Human Services announced that Dr. Robert Gallo and his colleagues at the National Cancer Institute (NCI) had confirmed the cause of acquired immunodeficiency syndrome (AIDS) as a retrovirus, which became known as human immunodeficiency virus (HIV) in 1986. For the past 40 years, prevention and cure of HIV infection have been the dual 'holy grail' sought but still not achieved. By the beginning of 2024, the World Health Organization (WHO) estimated that in the past 40 years, between 65.0 million and 113.0 million people have been infected with HIV, and between 32.9 million and 51.3 million people have died from HIV infection. On 29 February 2024, the WHO published an updated report in response to increasing reports of HIV drug resistance (HIVDR). Currently, HIV vaccines in development are in early-stage clinical trials. People with HIV are more likely to develop tuberculosis, with increasing rates of antimicrobial resistance. MTBVAC is the first live attenuated vaccine to prevent Mycobacterium tuberculosis infection, with phase 2a safety and efficacy clinical trial data expected at the end of 2024. This editorial aims to summarize the current challenges and hopes for developing vaccines to prevent HIV infection and approaches to overcome antiretroviral drug resistance as a cure for HIV/AIDS.

Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent ß-Thalassemia.

In 2020, Emmanuelle Charpentier and Jennifer Doudna were awarded the Nobel Prize in Chemistry for their research on the endonuclease, clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated protein 9 (CRISPR-Cas9) method for DNA editing. On 16 November 2023, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) was the first to approve the CRISPR-Cas9 gene editing therapy, Casgevy (exagamglogene autotemcel), for the treatment of patients with transfusion-dependent b-thalassemia and the treatment of sickle cell disease in patients aged ≥12 years with recurrent vaso-occlusive crises. On 8 December 2023, the US Food and Drug Administration (FDA) approved both Casgevy and Lyfgenia (lovotibeglogene autotemcel) for patients with sickle cell disease. On 15 December 2023, the European Medicines Agency (EMA) approved Casgevy for sickle cell disease and transfusion-dependent ß-thalassemia. This Editorial aims to present an update on the landmark first regulatory approvals of CRISPR-Cas9 for patients with sickle cell disease and transfusion-dependent b-thalassemia and the potential challenges for therapeutic gene (DNA) editing.

A Review of the Resurgence of Measles, a Vaccine-Preventable Disease, as Current Concerns Contrast with Past Hopes for Measles Elimination.

On 22 February 2024, the World Health Organization (WHO) stated that, following the recent resurgence of measles cases in Europe, more than half the world's countries could expect significant measles outbreaks this year. Measles is a highly infectious virus with a primary case reproduction number (R0) of 12-18. Measles infection can be severe, resulting in pneumonia, and also more rarely in subacute sclerosing panencephalitis (SSPE), which occurs in 1 child out of every 1,000 and can be fatal. Until the 1990s, the hope of eliminating measles seemed possible following the successful development of effective vaccines, given individually or in the combined measles, mumps, and rubella (MMR) vaccine. Vaccine hesitancy due to misinformation about possible vaccine side effects, reduced vaccine uptake during and after the COVID-19 pandemic, and lack of awareness of the severe consequences of measles infection have contributed to low vaccine uptake, resulting in vulnerable communities. This article aims to review the recent resurgence of measles cases in the US, Europe, and the UK, to provide a reminder of the potential severity of measles, and to consider the causes of the failure to eliminate this vaccine-preventable viral infection.

Editorial: Global Health Concerns as Vaccine-Preventable Infections Including SARS-CoV-2 (JN.1), Influenza, Respiratory Syncytial Virus (RSV), and Measles Continue to Rise.

In December 2023, the US Centers for Disease Control and Prevention (CDC) published the updated 2024 Advisory Committee on Immunization Practices (ACIP) Adult Immunization Schedule, which is available online for access by the public and healthcare professionals. These new guidelines come at a time when the incidence of vaccine-preventable viral infections from SARS-CoV-2 (JN.1), respiratory syncytial virus (RSV), influenza, and measles are increasing in adults and children due to vaccine hesitancy, or non-compliance. This editorial aims to highlight the ongoing global health concerns for the consequences of increasing reports of vaccine-preventable infections, including SARS-CoV-2 (JN.1), influenza, RSV, and measles, to understand the causes of vaccine hesitancy, and introduce some public health measures that could improve vaccine uptake.

Editorial: Climate Change and the Spread of Vector-Borne Diseases, Including Dengue, Malaria, Lyme Disease, and West Nile Virus Infection.

The major health threats from climate change include increasing temperatures, air pollution, extreme weather events, changes in the spread of infectious diseases, antimicrobial resistance, emerging pathogens, and an increase in vector-borne disease. Between October and December 2023, in 200 medical journal, epidemiologists, clinicians, healthcare policymakers, and journal editors published an emergency call to action to health professionals, the United Nations, and political leaders on climate change and its effects on the ecosystem and human health. Also, in December 2023, the Intergovernmental Panel on Climate Change (IPCC) published its sixth Assessment Report (AR6) that summarizes current knowledge, impacts, and health risks from climate change, as well as suggestions for mitigation and adaptation. For over a decade, the IPCC has reported that the prevalence of vector-borne diseases has increased and highlighted the importance of monitoring dengue, malaria, Lyme disease, West Nile virus infection, and other vector-borne diseases. This editorial aims to provide an update on the association between climate change and the spread of vector-borne diseases and highlights the urgent need for public health and disease prevention and treatment strategies to control the rise in vector-borne diseases.

A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and Future.

The clinical association of purpura, arthralgia, and arthritis was first described in 1837 in a publication by Johann Lukas Schönlein, a German physician. In 1874, Eduard Henoch, a student of Schönlein, reported cases of children with purpura, abdominal pain, bloody diarrhea, and joint pain. IgA vasculitis, or Henoch-Schönlein purpura, is a systemic hypersensitivity vasculitis caused by the deposition of immune complexes in small blood vessels, including the renal glomeruli and mesangium. In the skin, the presentation is with non-thrombocytopenic purpura or urticaria. Worldwide, IgA nephropathy is the most common cause of primary glomerulonephritis. Detection of IgA deposition in small blood vessels and the renal glomeruli is diagnostic in most cases. This article aims to review the history, current classification, epidemiology, presentation, and diagnosis of IgA vasculitis and nephropathy, disease associations or trigger factors, including infections, vaccines, and therapeutic agents, and highlights some future approaches to improve diagnosis and clinical management.

Editorial: Outbreaks of Post-Pandemic Childhood Pneumonia and the Re-Emergence of Endemic Respiratory Infections.

In October and November 2023, hospitals in the major cities of Beijing and Liaoning in northern China reported a surge in cases of pneumonia in children, with some hospitals being overwhelmed by pediatric emergency admissions. Similar outbreaks of childhood pneumonia had been reported in the autumn of 2022 in Europe and North America. Therefore, increased reports of childhood pneumonia could be driven by post-pandemic changes in the pathogenesis of endemic respiratory infections other than COVID-19, including Mycoplasma pneumoniae, respiratory syncytial virus (RSV), and influenza, rather than emerging novel pathogens. However, the recent reports of increased hospitalizations for children with pneumonia warrant continued infection surveillance and monitoring to exclude new respiratory pathogens or more virulent variants of known pathogens, including SARS-CoV-2. This editorial aims to present what is known about the re-emergence of endemic respiratory infections, which may be the cause of the recently reported outbreaks of childhood pneumonia.

Editorial: Factors Driving New Variants of SARS-CoV-2, Immune Escape, and Resistance to Antiviral Treatments as the End of the COVID-19 Pandemic is Declared.

On May 5, 2023, the Director-General of the World Health Organization (WHO) advised the transition to long-term management of the COVID-19 pandemic and that COVID-19 is now an established and ongoing health issue that is no longer a public health emergency of international concern (PHEIC). The WHO decision was based on an analysis of the decreasing trend in mortality, the decline in hospital admissions and Intensive Care Unit (ICU) admissions from COVID-19, and the increasing levels of population immunity to SARS-CoV-2. This Editorial aims to highlight what is known of the factors that drive new variants, subvariants, and lineages of SARS-CoV-2 associated with immune escape to previous infection or vaccines and resistance to antiviral treatments as the end of the COVID-19 pandemic is declared.

Editorial: Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 Guidelines for COPD, Including COVID-19, Climate Change, and Air Pollution.

The 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report includes relevant topics from the clinician's perspective and evidence published on chronic obstructive pulmonary disease (COPD) since GOLD 2017. The World Health Organization (WHO) and GOLD 2023 have developed an updated definition of COPD as, "a heterogeneous lung condition characterized by chronic respiratory symptoms (dyspnea, cough, expectoration, exacerbations) due to abnormalities of the airway (bronchitis, bronchiolitis) and/or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction." GOLD 2023 includes recommendations for COPD patients diagnosed with COVID-19 and acknowledges the role of reduced air quality in the etiology and progression of COPD. In May 2023, the GOLD Scientific Committee on Air Pollution and COPD reported that air pollution increasingly contributes to the pathogenesis of COPD. This Editorial aims to introduce the updated GOLD 2023 report in the context of climate change and the aftermath of the COVID-19 pandemic.

Editorial: The Increasing Relevance of Case Reports in Medical Education and Clinical Practice - and How to Write Them.

Between 2012 and 2022, the American Journal of Case Reports published over 3,500 case reports and case series. In 2022-23, this journal achieved an impact factor (IF) of 1.2. The significant merits of published case reports include identifying rare diseases and syndromes, treatment complications or side effects, pharmacovigilance, and medical education. The limitations or cautions of the case report include the inability to generalize, the lack of establishment of a cause-effect relationship, and over-interpretation. Historically, new clinical conditions and syndromes have been identified. Since 2020, the COVID-19 pandemic has significantly impacted manuscript submissions and publications, as illustrated for this journal. This editorial aims to highlight the importance of case reports and series, recent publication trends and includes recommendations on what to do and what not to do when preparing and writing the manuscript for a case report.

Editorial: A Rapid Global Increase in COVID-19 is Due to the Emergence of the EG.5 (Eris) Subvariant of Omicron SARS-CoV-2.

A new variant of SARS-CoV-2 has currently achieved global domination. EG.5 (Eris) was first reported by the World Health Organization (WHO) on February 17, 2023, and designated as a variant under monitoring (VUM) on July 19, 2023. EG.5 (Eris), and its sublineages, EG.5.1, EG.5.1.1, and EG.5.2, is a descendent lineage of XBB.1.9.2, which has the same spike amino acid profile as XBB.1.5 (Kraken). However, EG.5 (Eris) has an additional F456L amino acid mutation in the spike protein compared to these parent subvariants, and the subvariant EG.5.1 has another spike mutation, Q52H. Following risk evaluation by the WHO, EG.5 (Eris) and its sublineages were designated as a variant of interest (VOI) on August 8, 2023. In the US, the Centers for Disease Control and Prevention (CDC) provides two-weekly monitoring data on the incidence and mortality from COVID-19 and SARS-CoV-2 variants. The most recent CDC data for August 19, 2023, showed an increase in cases in the past two weeks, with hospitalizations for COVID-19 increasing by 14.3% and mortality from COVID-19 rising by 8.3%. In the US, the most common COVID-19 cases have been due to three new SARS-CoV-2 Omicron variants: EG.5 (Eris) (20.6%); FL.1.5.1 (Fornax) (13.3%); and XBB.1.16 (Arcturus) (10.7%). This Editorial aims to highlight the importance of rapid virus genomic sequencing and continued global SARS-CoV-2 surveillance to identify rapidly emerging SARS-CoV-2 Omicron variants, such as EG.5 (Eris).

Editorial: First Regulatory Approval for Allogeneic Pancreatic Islet Beta Cell Infusion for Adult Patients with Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus affects adults and children, with an increasing number of newly-diagnosed cases each year. Type 1 diabetes involves a primary functional defect in pancreatic islet beta cells, resulting in secondary autoimmunity that results in T-cell-mediated beta cell death. However, pancreatic transplantation is a complex procedure, with complications that include transplant organ failure due to rejection or ischemia-reperfusion injury, safety issues of the duodenal-duodenal anastomosis technique, and the availability of segmental or whole organs. On June 28, 2023, the FDA Center for Biologics Evaluation and Research (CBER) approved Lantidra (donislecel), the first allogeneic (deceased donor) pancreatic islet cell therapy for the treatment of adults with type 1 diabetes who do not achieve target glycated hemoglobin levels because of repeated episodes of severe hypoglycemia, despite current management. This Editorial aims to highlight the increasing global health burden of type 1 diabetes, previous approaches to pancreatic transplant methods and introduces the first regulatory approval for allogeneic pancreatic islet beta cell infusion, a novel approach to transplantation.