Baloxavir Marboxil: An Original New Drug against Influenza

Baloxavir marboxil is a new drug developed in Japan by Shionogi to treat seasonal flu infection. This cap-dependent endonuclease inhibitor is a prodrug that releases the biologically active baloxavir acid. This new medicine has been marketed in Japan, the USA and Europe. It is well tolerated (more than 1% of the patients experienced diarrhea, bronchitis, nausea, nasopharyngitis, and headache), and both influenza A and B viruses are sensitive, although the B strain is more resistant due to variations in the amino acid residues in the binding site. The drug is now in post-marketing pharmacovigilance phase, and its interest will be especially re-evaluated in the future during the annual flu outbreaks. It has been also introduced in a recent clinical trial against COVID-19 with favipiravir.

Reappraisal of metabolic dysfunction in neurodegeneration: Focus on mitochondrial function and calcium signaling

The cellular and molecular mechanisms that drive neurodegeneration remain poorly defined. Recent clinical trial failures, difficult diagnosis, uncertain etiology, and lack of curative therapies prompted us to re-examine other hypotheses of neurodegenerative pathogenesis. Recent reports establish that mitochondrial and calcium dysregulation occur early in many neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson’s disease, Huntington's disease, and others. However, causal molecular evidence of mitochondrial and metabolic contributions to pathogenesis remains insufficient. Here we summarize the data supporting the hypothesis that mitochondrial and metabolic dysfunction result from diverse etiologies of neuropathology. We provide a current and comprehensive review of the literature and interpret that defective mitochondrial metabolism is upstream and primary to protein aggregation and other dogmatic hypotheses of NDDs. Finally, we identify gaps in knowledge and propose therapeutic modulation of mCa2+ exchange and mitochondrial function to alleviate metabolic impairments and treat NDDs.

Cognitive-Reminiscence Therapy for Young Adults with Depressive Symptoms: Clinical Observations, Challenges, and Recommendations

Cognitive-reminiscence therapy is a novel intervention for depression in young adults, and currently no specific clinical guidance exists for its use in this age group. The aim of this article is to disseminate our experiences from a recent clinical trial in which we engaged in cognitive-reminiscence therapy (CRT) with young adults for the purpose of treating depressive symptoms. Discussion is presented in terms of clinical observations that were made during treatment, specific challenges that arose, and recommendations for implementing this therapy with young adults. Firstly, a conceptual overview and rationale for CRT is provided along with an outline of the treatment protocol that was used. Then,a framework for undertaking therapeutic reminiscence work at different levels of analysis is presented, and comment is made on the rationale for, and the process of, elicitingspecific memories. Common life events and issues that emerged as the foci of reminiscence with young adults in our trial are reviewed. Following this, the process of orienting to the mechanisms of change in CRT is discussed. Finally, several clinical issues and insights that emerged during the provision of this therapy are presented: contextualising emerging adulthood as a time of transition, creating continuity acrossindividuals’ lives, the process of reflection on reminiscence, and homework adherence.

Use of Interferon Alfa in the Treatment of Myeloproliferative Neoplasms: Perspectives and Review of the Literature

Interferon alfa was first used in the treatment of myeloproliferative neoplasms (MPNs) over 30 years ago. However, its initial use was hampered by its side effect profile and lack of official regulatory approval for MPN treatment. Recently, there has been renewed interest in the use of interferon in MPNs, given its potential disease-modifying effects, with associated molecular and histopathological responses. The development of pegylated formulations and, more recently, ropeginterferon alfa-2b has resulted in improved tolerability and further expansion of interferon’s use. We review the evolving clinical use of interferon in essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). We discuss interferon’s place in MPN treatment in the context of the most recent clinical trial results evaluating interferon and its pegylated formulations, and its role in special populations such as young and pregnant MPN patients. Interferon has re-emerged as an important option in MPN patients, with future studies seeking to re-establish its place in the existing treatment algorithm for MPN, and potentially expanding its use for novel indications and combination therapies.

Nanogels as nanocarriers for drug delivery: A review

Nanogels are submicron-size aqueous dispersions of water-swollen particles, composed of nano-sized three-dimensional highly cross-linked networks of hydrophilic polymers. An active pharmaceutical agent or therapeutic agent with high or low molecular weight can be easily encapsulated into nanogels that can be delivered to the site of action via various routes, including oral, pulmonary, nasal, parenteral and intraocular routes, among others. Therapeutic agents encapsulated into nanogels improve the therapeutic activity in the biological environment. The application of different nanogels in drug delivery and recent clinical trial studies has been described concisely in this review.

Antibiotic Duration, but Not Abscess Size, Impacts Clinical Cure of Limited Skin and Soft Tissue Infection After Incision and Drainage

Antibiotics are frequently prescribed following incision and drainage of cutaneous abscesses. In subgroup analyses from a recent clinical trial, we observed higher likelihood of cure with antibiotic courses beyond 5 or 7 days (up to 10). Among this cohort, for abscesses ≤5 cm, size did not modify the antibiotic effect.

TMIC-54. COMPARISON OF CELLULAR FEATURES AT AUTOPSY IN GLIOBLASTOMA PATIENTS WITH STANDARD TREATMENT OF CARE AND TUMOR TREATMENT FIELDS

BACKGROUND The FDA has approved the use of tumor treatment fields (TTFields) on patients with recurrent glioblastoma (GBM). A recent clinical trial showed that the use of TTFields along with standard treatment of care resulted in increased quality of life and survival over five years. TTFields work by delivering low intensity electric fields that disrupt GBM tumor cell division. This works to slow or even stop GBM tumor cells from dividing. METHODS Brain tissue samples were taken from thirteen GBM patients, diagnosed at autopsy. Three patients underwent standard clinical treatment and ten patients underwent TTField therapy in addition to the standard. Tissue samples were acquired from regions where enhancement was seen on the last clinical T1 plus contrast MRI prior to death. Samples were paraffin embedded and stained with hematoxylin and eosin (H&E) and Ki67. The slides were digitized, allowing analysis of the cellular features. RESULTS Using the H&E stained slides we compared cellular density between both groups. We found that there was not a noticeable difference in the nuclei density in areas of tumor between the groups. The percent of positive nuclei on the Ki67 stained slides was calculated and there was increased mitotically active cells per area of tissue in patients that did not undergo TTField therapy. CONCLUSION These findings suggest there is a difference in the cellular features in areas of tumor in patients treated with TTFields compared to those with standard treatment alone. Additional research needs to be done evaluating more patients.

The Development of Tumor Neoantigen Vaccine Immunotherapy

Activating the immune system to fight against cancers has long been a goal in immunology and oncology studies. Recent clinical-trial data proved that boosting the activity of endogenous T cells to destroy cancer cells has great potential in controlling the progression of a variety of human malignancies. In essence, neoantigen is at the core of tumor immunology. Autologous T lymphocytes could distinguish tumor cells from normal cells by recognizing neoantigens, which are tumor specific. Neoantigens are derived from genome somatic mutations of tumors, and there are different approaches to predict and identify them with increasing accuracy. Neoantigens are tumor specific, which are ideal and attractive targets for tumor immunotherapies; many neoantigen-based clinical trials are being carried out around the world. In this review, we will discuss the recent advances of tumor neoantigen vaccine immunotherapy, and present the potential obstacle and future direction of this approach.

Conversion of RpoS− Attenuated Salmonella enterica Serovar Typhi Vaccine Strains to RpoS+ Improves Their Resistance to Host Defense Barriers

Recombinant attenuatedSalmonellavaccines (RASVs) represent a unique prevention strategy to combating infectious disease because they utilize the ability ofSalmonellato invade and colonize deep effector lymphoid tissues and deliver hetero- and homologous derived antigens at the lowest immunizing dose. Our recent clinical trial in human volunteers indicated that an RpoS+derivative of Ty2 was better at inducing immune responses than its RpoS−counterpart. In this study, we demonstrate that a functional RpoS allele is beneficial for developing effective live attenuated vaccines againstS. Typhi or in usingS. Typhi as a recombinant attenuated vaccine vector to deliver other protective antigens.