US Food Research Articles

Exploring Protein Dietary Guidance Statements

Consumers may benefit from quick signals on or nearby food product to nudge them toward choosing healthier diets, such as Dietary Guidance Statements (DGSs) from the US Food and Drug Administration. It is unclear how DGSs on foods, including animal or plant proteins, impact purchase motivation, believability, or willingness to pay more. Six DGS claims were tested across 5 protein types (pork tenderloin, beef top sirloin fillet, chicken breast, turkey breast, and plant-based meat) using an online prediction market test survey format among 1002 nationally representative US-based household primary grocery shoppers aged 18 to 64 years. The most motivating and believable DGS across protein types was the Dietary Guidelines DGS: The Dietary Guidelines for Americans recommends eating 5½ oz of protein food per day as part of a nutritious dietary pattern. <protein type> is a lean meat that provides 3 oz of protein food per serving (based on a 2000-calorie diet). More than one-third felt that this Dietary Guidelines DGS was the most motivating and believable because it was informative; imparted feelings of the protein type being healthy; contained statistics, facts, or numbers; and mentioned the US Dietary Guidelines for Americans. More than 50% of participants were willing to pay at least 5% or more for the protein type specified in the Dietary Guidelines DGS across all protein types. Uniform adoption of DGSs across protein food groups allows for equal representation of how a variety of proteins can contribute to a nutritious dietary pattern.

ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma

PURPOSE Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration–approved for adults. METHODS ReNeu is an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in 58 adults (≥18 years of age) and 56 children (2 to 17 years of age) with NF1-PN causing significant morbidities. Patients received mirdametinib capsules or tablets for oral suspension (2 mg/m 2 twice daily, maximum 4 mg twice daily), regardless of food intake, in 3 weeks on/1 week off 28-day cycles. The primary end point was confirmed objective response rate (ORR; proportion of patients with a ≥20% reduction of target PN volume from baseline on consecutive scans during the 24-cycle treatment phase) assessed by blinded independent central review (BICR) of volumetric magnetic resonance imaging. RESULTS Twenty-four of 58 adults (41%) and 29 of 56 children (52%) had a BICR-confirmed objective response during the 24-cycle treatment phase; in addition, two adults and one child had confirmed responses during long-term follow-up. Median (range) target PN volumetric best response was –41% (−90 to 13) in adults and –42% (−91 to 48) in children. Both cohorts reported significant and clinically meaningful improvement in patient- or parent proxy-reported outcome measures of worst tumor pain severity, pain interference, and health-related quality of life (HRQOL) that began early and were sustained during treatment. The most commonly reported treatment-related adverse events were dermatitis acneiform, diarrhea, and nausea in adults and dermatitis acneiform, diarrhea, and paronychia in children. CONCLUSION In ReNeu, the largest multicenter NF1-PN trial reported to date, mirdametinib treatment demonstrated significant confirmed ORRs by BICR, deep and durable PN volume reductions, and early, sustained, and clinically meaningful improvement in pain and HRQOL. Mirdametinib was well-tolerated in adults and children.

Consensus Report on Glucagon-Like Peptide-1 Receptor Agonists as Adjunctive Treatment for Individuals With Type 1 Diabetes Using an Automated Insulin Delivery System

With increasing prevalence of obesity and cardiovascular diseases, there is a growing interest in the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as an adjunct therapy in type 1 diabetes (T1D). The GLP-1RAs are currently not approved by the US Food and Drug Administration for the treatment of T1D in the absence of randomized controlled trials documenting efficacy and safety of these agents in this population. The Diabetes Technology Society convened a series of three consensus meetings of clinicians and researchers with expertise in diabetes technology, GLP-1RA therapy, and T1D management. The project was aimed at synthesizing current literature and providing conclusions on the use of GLP-1RA therapy as an adjunct to automated insulin delivery (AID) systems in adults with T1D. The expert panel members met virtually three times on January 17, 2024, and April 24, 2024, and August 14, 2024, to discuss topics ranging from physiology and outcomes of GLP-1RAs in T1D to limitations of current sensors, algorithms, and insulin for AID systems. The panelists also identified research gaps and future directions for research. The panelists voted to in favor of 31 recommendations. This report presents the consensus opinions of the participants that, in adults with T1D using AID systems, GLP-1RAs have the potential to (1) provide effective adjunct therapy and (2) improve glycemic and metabolic outcomes without increasing the risk of severe hypoglycemia or diabetic ketoacidosis.

The Antipsychotic Drug Aripiprazole Suppresses Colorectal Cancer by Targeting LAMP2a to Induce RNH1/miR‐99a/mTOR‐Mediated Autophagy and Apoptosis

AbstractThe mammalian target of rapamycin (mTOR) is a critical signaling hub for sustaining cancer survival. Targeting mTOR and inducing autophagic cell death downstream of it represent promising therapeutic strategies for cancer prevention. A US Food and Drug Administration‐approved drug library containing 616 small molecules is used to screen anticancer drugs against colorectal cancer (CRC) cells that rely on mTOR. This led to the identification of an antipsychotic drug aripiprazole, which significantly induced mTOR inhibition and autophagic apoptosis in CRC, in vitro and in vivo. The use of drug affinity response target stability identified lysosome‐associated membrane protein 2A (LAMP2a) as a direct target of aripiprazole. LAMP2a‐deficient CRC cells are refractory to aripiprazole. High LAMP2a expression is associated with poor survival of patients with CRC and negatively correlated with expression of ribonuclease inhibitor 1 (RNH1), which is later confirmed as a novel substrate of LAMP2a. Mechanistically, aripiprazole bound to the Lys401–His404 of LAMP2a and repressed its activity, subsequently inactivating RNH1/miR‐99a/mTOR signaling and inducing autophagy‐mediated apoptosis, thereby suppressing tumorigenesis. Liposome‐mediated delivery of aripiprazole in combination with fluorouracil elicited superior therapeutic benefits in CRC, as compared to single treatments, thereby highlighting that aripiprazole may be repurposed as a novel therapeutic agent for CRC treatment.

Postmarketing Surveillance of Inferior Vena Cava Filters Among US Medicare Beneficiaries

Inferior vena cava filters (IVCFs) are commonly used to prevent pulmonary embolism in selected clinical scenarios, despite limited evidence to support their use. Current recommendations from professional societies and the US Food and Drug Administration endorse timely IVCF retrieval when clinically feasible. Current IVCF treatment patterns and outcomes remain poorly described. To evaluate temporal trends and practice patterns in IVCF insertion and retrieval among older US patients and report the incidence of periprocedural and long-term safety events of indwelling and retrieved IVCFs. Prespecified, retrospective, observational cohort of Medicare Fee-for-Service (FFS) beneficiaries, leveraging 100% of samples of inpatient and outpatient claims data from January 1, 2013, to December 31, 2021. First-time IVCF insertion while insured by Medicare FFS. The primary safety outcome was the composite of all-cause death, filter-related complications (eg, fracture, embolization), operating room visits following filter-related procedures, or new diagnosis of deep vein thrombosis (DVT). Events were considered periprocedural if they occurred within 30 days of IVCF insertion or retrieval and long-term if they occurred more than 30 days after. Among 270 866 patients with IVCFs placed during the study period (mean age, 75.1 years; 52.8% female), 64.9% were inserted for first-time venous thromboembolism (VTE), 26.3% for recurrent VTE, and 8.8% for VTE prophylaxis. Of these patients, 63.3% had major bleeds or trauma within 30 days of IVCF insertion. The volume of insertions decreased from 44 680 per year in 2013 to 19 501 per year in 2021. The cumulative incidence of retrieval was 15.3% at a median of 1.2 years and 16.8% at maximum follow-up of 9.0 years. Older age, more comorbidities, and Black race were associated with a decreased likelihood of retrieval, whereas placement at a large teaching hospital was associated with an increased likelihood of retrieval. The incidence of caval thrombosis and DVT among patients with nonretrieved IVCFs was 2.2% (95% CI, 2.1%-2.3%) and 9.2% (95% CI, 9.0%-9.3%), respectively. The majority (93.5%) of retrieval attempts were successful, with low incidence of 30-day complications (mortality, 0.7% [95% CI, 0.6%-0.8%]; filter-related complications, 1.4% [95% CI, 1.2%-1.5%]). In this large, US real-world analysis, IVCF insertion declined, yet retrievals remained low. Strategies to increase timely retrieval are needed, as nonretrieved IVCFs may have long-term complications.

Nociceptor-to-macrophage communication through CGRP/RAMP1 signaling drives endometriosis-associated pain and lesion growth in mice.

Endometriosis is a debilitating and painful gynecological inflammatory disease affecting up to 15% of women and transgender men. Current treatments are ineffective for a substantial proportion of patients, underscoring the need for additional therapies with long-term benefits. Nociceptors release neuropeptides, such as calcitonin gene-related peptide (CGRP), which are known to shape immunity through neuroimmune communication. Given the comorbidity between endometriosis and migraine and the integral role of immune cells and inflammation in endometriosis, we investigated the role of CGRP-mediated neuroimmune communication in endometriosis. Using samples from eight patients with endometriosis and a nonsurgical mouse model of the disease, we found that mouse and human endometriosis lesions contain both CGRP and its coreceptor, receptor activity modifying protein 1 (RAMP1). In mice, nociceptor ablation reduced pain, monocyte recruitment, and lesion size, suggesting that nociceptor activation and neuropeptide release contribute to endometriosis lesion growth and pain. Mechanistically, CGRP changed the phenotype of macrophages to a pro-endometriosis phenotype. CGRP-stimulated macrophages demonstrated impaired efferocytosis and supported increased endometrial cell growth in a RAMP1-dependent manner. Treatment of lesion-bearing mice with US Food and Drug Administration-approved drugs that block CGRP-RAMP1 signaling reduced mechanical hyperalgesia, spontaneous pain, and lesion size. Together, our data demonstrated the effectiveness and underlying cellular mechanisms of nonhormonal and nonopioid CGRP/RAMP1 blockade in a mouse model of endometriosis, suggesting that targeting this axis may lead to clinical benefit for patients with endometriosis.

Identification of small molecule agonists of fetal hemoglobin expression for the treatment of sickle cell disease.

Induction of fetal hemoglobin (HbF) has been shown to be a viable therapeutic approach to treating sickle cell disease and potentially other β-hemoglobinopathies. To identify targets and target-modulating small molecules that enhance HbF expression, we engineered a human umbilical-derived erythroid progenitor reporter cell line (HUDEP2_HBG1_HiBiT) by genetically tagging a HiBiT peptide to the carboxyl (C)-terminus of the endogenous HBG1 gene locus, which codes for γ-globin protein, a component of HbF. Employing this reporter cell line, we performed a chemogenomic screen of approximately 5000 compounds annotated with known targets or mechanisms that have achieved clinical stage or approval by the US Food and Drug Administration (FDA). Among them, 10 compounds were confirmed for their ability to induce HbF in the HUDEP2 cell line. These include several known HbF inducers, such as pomalidomide, lenalidomide, decitabine, idoxuridine, and azacytidine, which validate the translational nature of this screening platform. We identified avadomide, autophinib, triciribine, and R574 as novel HbF inducers from these screens. We orthogonally confirmed HbF induction activities of the top hits in both parental HUDEP2 cells as well as in human primary CD34+ hematopoietic stem and progenitor cells (HSPCs). Further, we demonstrated that pomalidomide and avadomide, but not idoxuridine, induced HbF expression through downregulation of several transcriptional repressors such as BCL11A, ZBTB7A, and IKZF1. These studies demonstrate a robust phenotypic screening workflow that can be applied to large-scale small molecule profiling campaigns for the discovery of targets and pathways, as well as novel therapeutics for sickle cell disease and other β-hemoglobinopathies.

Online Interest in Elf Bar in the United States: Google Health Trends Analysis.

Despite the popularity of JUUL e-cigarettes, other brands (eg, Elf Bar) may be gaining digital attention. This study compared Google searches for Elf Bar and JUUL from 2022 to 2023 using Google Health Trends Application Programming Interface data. Using an infodemiology approach, we examined weekly trends in Google searches (per 10 million) for "Elf Bar" and "JUUL" at the US national and state levels from January 1, 2022, to December 31, 2023. Joinpoint regression was used to assess statistically significant trends in the search probabilities for "Elf Bar" and "JUUL" during the study period. Elf Bar had less online interest than JUUL at the beginning of 2022. When the US Food and Drug Administration denied JUUL marketing authority on June 23, 2022, JUUL searches peaked at 2609.3 × 107 and fell to 83.9 × 107 on September 3, 2023. Elf Bar searches surpassed JUUL on July 10, 2022, and steadily increased, reaching 523.2 × 107 on December 4, 2022. Overall, Elf Bar's weekly search probability increased by 1.6% (95% CI 1.5%-1.7%; P=.05) from January 2022 to December 2023, with the greatest increase between May 29 and June 19, 2022 (87.7%, 95% CI 35.9%-123.9%; P=.001). Elf Bar searches increased after JUUL's suspension in Pennsylvania (1010%), Minnesota (872.5%), Connecticut (803.5%), New York (738.1%), and New Jersey (702.9%). Increasing trends in Google searches for Elf Bar indicate that there was a growing online interest in this brand in the United States in 2022.

Update on Mpox Management: Epidemiology, Vaccines and Therapeutics, and Regulatory Changes.

Mpox, caused by the monkeypox virus (MPXV), is categorized into two primary clades: Clade I and Clade II, with notable outbreaks linked to Clade IIb. Historically endemic in Africa, recent years have seen significant global spread. The World Health Organization (WHO) declared mpox a Public Health Emergency of International Concern in August 2024, highlighting the emergence of Clade Ib outside Africa and the broadening demographic impact of the outbreak. This review updates the current status of mpox vaccines and treatments, including their safety and effectiveness. There are two US Food and Drug Administration (FDA)-approved vaccines for the prevention of mpox disease, JynneosTM and ACAM2000®. The JynneosTM vaccine, recommended for high-risk individuals, has seen limited uptake despite its efficacy in preventing disease. Tecovirimat, while FDA-approved for smallpox and available in the European Union for mpox, has shown mixed results in recent trials, with new data suggesting limited effectiveness in Clade I infections and emergence of new mutations with resistance to this drug. Brincidofovir and Vaccinia Immune Globulin Intravenous offer additional treatment options, particularly for severe cases, although their use is constrained by regulatory and logistical challenges. Furthermore, the WHO recently approved the first commercial molecular assay, the Alinity m MPXV assay by Abbott Molecular Inc., for emergency use-an essential step in expanding testing capacity in regions experiencing mpox outbreaks. These updates underscore the critical need for continued research to enhance therapeutic outcomes and adapt public health strategies. Ensuring equitable access to vaccines, treatments, and diagnostics remains a significant challenge as the global community responds to the evolving mpox situation.

Dietary assessments in individuals living with coeliac disease: key considerations.

Coeliac disease (CeD) is a type of enteropathy characterised by an immune-mediated reaction to ingested gluten, resulting in impaired absorption of nutrients and symptoms such as bloating, abdominal cramping and diarrhoea. Currently, the only treatment for CeD is adherence to a gluten-free diet (GFD). The latest draft guidance from the US Food and Drug Administration recommends that dietitians experienced in CeD management evaluate patients during the screening and treatment period of CeD clinical trials to assess adherence to a GFD. However, there are currently no standardised guidelines on dietary assessment of patients with CeD on a GFD and there is a lack of widespread availability of expertise in this field. Based on the findings of a literature review conducted between April and September 2023, this article provides an overview of key points to consider in the nutritional and dietary assessment of patients with CeD who are following a GFD, with particular focus on the clinical trial setting. Based on a consensus from dietitians and gastroenterologists experienced in treating patients with CeD, we present specific recommendations for registered dietitians who manage patients with CeD. We also describe the development of a simplified tool for assessment of adherence to a GFD, the Gluten-Free Adherence Survey, based on these recommendations. These guidelines cover nutritional and dietary assessment of patients with CeD, physical assessments, intake of oats, environmental considerations and the disease burden.

An update on the pharmacotherapy of postpartum depression.

Extensive research has been conducted on postpartum depression (PPD) over the past century, and yet no definitive answer regarding its etiopathogenesis, risk factors, genetic predilection, and treatment has been found. The few preclinical and clinical studies propose that maternal brain adaptations to the endocrinological, immunological, and behavioral changes and external sociodemographic risk factors in the perinatal period make women more vulnerable to anxiety and depression. Irrespective of the cause, a dilemma exists regarding the type of help to provide postpartum mothers. With very few treatment options at our disposal, deciding between psychotherapy, pharmacological, and non-pharmacological therapy on a case-by-case basis is unproductive because in developing countries infrastructure is limited and the availability of medications, especially for psychiatric illnesses, is still evolving. Hence, regardless of psychotherapy, antidepressants remain the first line of treatment with selective serotonin reuptake inhibitors (SSRIs); sertraline has the best efficacy and safety profile in breastfeeding women. As endocrine factors play a significant role in etiopathogenesis, hormonal therapy with oxytocin has been shown to be efficacious, and studies investigating the role of testosterone in treating PPD are also under way. In 2019, the US Food and Drug Administration (FDA) approved the first and only drug for the sole purpose of treating PPD, brexanolone. Zuranolone, a drug recently approved by the FDA, has a similar mechanism of action to brexanolone. For breastfeeding mothers reluctant to use pharmacotherapy, somatic therapy has been studied, including bright light therapy, vagal nerve stimulation, and newer noninvasive interventions. This article encompasses a short note on PPD, including its etiopathogenesis and clinical characteristics, and recapitulates the various available and evolving pharmacological and nonpharmacological therapies.

Fecal Microbiota, Live-jslm (RBL; REBYOTA™) for Recurrent Clostridioides difficile Infection

Clostridioides difficile infection (CDI) is one of the most common causes of health care–associated infections and is often precipitated by recent antibiotic use. CDI occurs after the healthy gut microbiota is disrupted and becomes dysbiotic. Standard-of-care antibiotics for CDI may perpetuate dysbiosis, fueling risk of recurrent CDI (rCDI). New therapeutic options for preventing rCDI include fecal microbiota, live-jslm (RBL), a US Food and Drug Administration–approved, single-dose, rectally administered, microbiota-based live biotherapeutic product. RBL, which is easily given by any health care professional, is hypothesized to assist in restoring dysbiosis and has proven efficacy, safety, and tolerability across diverse patient populations to prevent rCDI.

The Food and Drug Administration’s Safety Surveillance of Adverse Event Cases Involving Cannabinoid Hemp Products, 2019–2023

Objective. To characterize adverse event (AE) cases received by the US Food and Drug Administration (FDA) reportedly involving cannabinoid hemp products (CHPs). Methods. We searched the FDA Adverse Event Reporting System and Center for Food Safety and Applied Nutrition Adverse Event Reporting System for cases reported directly to the FDA from 2019–2023 involving CHPs, which are defined as products containing 1 or more of the following: cannabidiol, delta-8 tetrahydrocannabinol, and emerging cannabinoids (i.e., other intoxicating cannabinoids often synthesized from hemp-derived cannabidiol). We abstracted and summarized information on reporting trends, consumer demographics, reporter information, product information, and AEs. Results. We identified 610 AE cases reportedly involving CHPs containing 1 or more of the following: delta-8 tetrahydrocannabinol (n=355), cannabidiol (n=253), and emerging cannabinoids (n=36). Multiple trends and safety issues were identified, including an annual increase in the number of cases involving intoxicating cannabinoids since 2021, potential quality issues, and the occurrence of fatalities and pediatric exposures. Conclusions. Our findings emphasize the importance of monitoring AE cases received by the FDA involving CHPs as part of a comprehensive surveillance strategy to identify trends and safety issues with these products. ( Am J Public Health. 2024;114(S8):S664–S672. https://doi.org/10.2105/AJPH.2024.307712 )

GA2LEN ANACARE consensus statement: Potential of omalizumab in food allergy management.

Immunoglobulin E (IgE)-mediated food allergies are the most common type of food allergy, often causing rapid symptoms after exposure to allergens posing a serious health risk and a high impact on patient's and caregiver's quality of life. Omalizumab, a humanized anti-IgE monoclonal antibody, reduces allergic reactions by binding to circulating IgE. Omalizumab has been successfully used in allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic urticaria, and was recently approved for treating IgE-mediated food allergies by the US Food and Drug Administration (FDA). This GA2LEN ANACARE Consensus Statement presents our position on the use of omalizumab for treating IgE-mediated food allergies, based on a systematic review and meta-analysis, experience with use for other conditions, and expert consensus achieved via an eDelphi process. Following publication of the recent OUtMATCH study (stage 1) results and subsequent FDA approval, we propose that there is now sufficient evidence to recommend omalizumab as the only drug currently available that can mechanistically reduce IgE-mediated food allergic reactions. We acknowledge that the evidence does not reach the highest level of evidence which would be needed for a guideline recommendation.

Optimized psilocybin production in tryptophan catabolism-repressed fungi.

The high therapeutic potential of psilocybin, a prodrug of the psychotropic psilocin, holds great promise for the treatment of mental disorders such as therapy-refractory depression, alcohol use disorder and anorexia nervosa. Psilocybin has been designated a 'Breakthrough Therapy' by the US Food and Drug Administration, and therefore a sustainable production process must be established to meet future market demands. Here, we present the development of an invivo psilocybin production chassis based on repression of l-tryptophan catabolism. We demonstrate the proof of principle in Saccharomyces cerevisiae expressing the psilocybin biosynthetic genes. Deletion of the two aminotransferase genes ARO8/9 and the indoleamine 2,3-dioxygenase gene BNA2 yielded a fivefold increase of psilocybin titre. We transferred this knowledge to the filamentous fungus Aspergillus nidulans and identified functional ARO8/9 orthologs involved in fungal l-tryptophan catabolism by genome mining and cross-complementation. The double deletion mutant of A. nidulans resulted in a 10-fold increased psilocybin production. Process optimization based on respiratory activity measurements led to a final psilocybin titre of 267 mg/L in batch cultures with a space-time-yield of 3.7 mg/L/h. These results demonstrate the suitability of our engineered A. nidulans to serve as a production strain for psilocybin and other tryptamine-derived pharmaceuticals.

Participant Diversity in Stroke‐Related Medical Device Trials: Historical Context and Ongoing Challenges

Despite an acknowledgment of the ethical and clinical importance of recruiting diverse populations into clinical trials, there is a continued underenrollment of patients with diverse demographic characteristics within the field of neurology and more specifically, in stroke‐related device trials. Efforts on the part of the US Congress, the National Institutes of Health, the US Food and Drug Administration, and the Centers for Medicare & Medicaid Services over the past several decades have attempted to increase trial participant diversity with varying success. This historical context provides an important lens for analyzing diversity proposals and their bearing on device trials in the field of stroke neurology. Despite economic and logistical challenges, recruitment of appropriately diverse clinical trial populations through policy change and community engagement is critical to continuing to advance health equity goals.

Flexible Development Programs for Antibacterial Drugs to Address Unmet Medical Needs.

The US Food and Drug Administration recognizes the unmet medical need for antibacterial drugs to treat serious bacterial diseases caused by resistant pathogens for which effective therapies are limited or lacking. The agency also recognizes that designing and conducting clinical trials to assess the safety and efficacy of drugs to treat resistant infections is challenging, especially for drugs only active against a single or a few bacterial species, and that a more flexible development program might be appropriate. In this article, we discuss several regulatory considerations for flexible development programs for antibacterial drugs intended to meet an unmet medical need. As an example, we use the recent approval of sulbactam for injection and durlobactam for injection (XACDURO) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.

Glutamatergic Modulators for Major Depression from Theory to Clinical Use.

Major depressive disorder (MDD) is a chronic, burdensome, highly prevalent disease that is characterized by depressed mood and anhedonia. MDD is especially burdensome as approved monoamine antidepressant treatments have weeks-long delays before clinical benefit and low remission rates. In the past 2decades, a promising target emerged to improve patient outcomes in depression treatment: glutamatergic signaling. This narrative review provides a high-level overview of glutamate signaling in synaptogenesis and neural plasticity and the implications of glutamate dysregulation in depression. Based on this preclinical evidence implicating glutamate in depression and the rapid improvement of depression with ketamine treatment in a proof-of-concept trial, a range of N-methyl-D-aspartate (NMDA)-targeted therapies have been investigated. While an array of treatments has been investigated in registered phase 2 or 3 clinical trials, the development of most of these agents has been discontinued. Multiple glutamate-targeted antidepressants are actively in development, and two are approved. Nasal administration of esketamine (Spravato®) was approved by the US Food and Drug Administration (FDA) in 2019 to treat adults with treatment-resistant depression and in 2020 for adults with MDD with acute suicidal ideation or behavior. Oral combination dextromethorphan-bupropion (AXS-05, Auvelity® extended-release tablet) was FDA approved in 2022 for the treatment of MDD in adults. These approvals bolster the importance of glutamate in depression and represent an exciting breakthrough in contemporary psychiatry, providing new avenues of treatment for patients as first-line therapy or with either poor response or unacceptable side effects to monoaminergic antidepressants.

Utility and Safety of 5-ALA Guided Surgery in Pediatric Brain Tumors: A Systematic Review

Background: 5-Aminolevulinic acid-guided surgery for adult gliomas has been approved by the European Medicines Agency and the US Food and Drug Administration, becoming a reliable tool for improving gross total resection rates and patient outcomes. This has led several medical centers to explore the off-label use of 5-ALA in the resection of pediatric brain tumors, assessing its efficacy and safety across various tumor types. However, given the differences between children and adults, the appropriateness of 5-ALA use in pediatric populations has not yet been fully established. Methods: We collected eligible publications from Embase, Scopus, PubMed, and Proquest, ultimately selecting 27 studies. Data extraction and retrospective analysis of 249 surgical cases were conducted to determine the current efficacy and safety of 5-ALA in pediatric brain tumors. The fluorescence rate and utility stratified by several clinical features, including WHO grade, tumor classification, and tumor location, were analyzed. Results: Most studies suggest that 5-ALA can enhance tumor identification in high-grade tumors, including glioblastomas and anaplastic astrocytomas. Changes in survival or recurrence rates associated with 5-ALA-guided resection have not been reported. None of the cases reported significant postoperative complications related to the use of 5-ALA. Conclusions: 5-ALA can aid in the resection of high-grade gliomas in pediatric patients. The efficacy of 5-ALA in low-grade gliomas and other tumors may require enhancement with additional tools or modified administration protocols. The safety of 5-ALA has reached a preliminary consensus, although further randomized controlled trials and data on survival and molecular characteristics are needed.

Scalable solutions for global health: the SalivaDirect model

The COVID-19 pandemic caught the world unprepared. Large-scale testing efforts were urgently needed, and diagnostic strategies had to rapidly evolve in response to unprecedented worldwide demand. However, the rollout of diagnostic testing and screening for SARS-CoV-2 was often impeded by logistical challenges, including regulatory delays, workforce shortages, laboratory bottlenecks, and supply chain disruptions. Recognizing these hurdles early on, we developed a testing approach that supported frequent, repeat testing, particularly as communities reopened. We hypothesized and experimentally demonstrated that saliva was a suitable specimen for the detection of SARS-CoV-2. This finding was advanced into the development of open-source, extraction-free reverse transcription polymerase chain reaction protocols using readily available, “off-the-shelf” reagents and equipment for the direct detection of SARS-CoV-2 in saliva (“SalivaDirect’’). Working with the US Food and Drug Administration (FDA), we established a novel regulatory framework wherein the FDA granted Emergency Use Authorization to Yale University to offer the SalivaDirect test protocol to high-complexity diagnostic laboratories (as designated by the Clinical Laboratory Improvement Amendments) with quality oversight provided by Yale. This grew into a network of more than 200 labs across the United States that, as of May 2024, resulted in over 6.5 million SARS-CoV-2 tests. By making the protocol flexible and open-source, laboratories were able to rapidly and economically scale testing using a simple, self-collected saliva specimen. Additionally, fostering a national network of laboratories enabled real-time exchanges, problem solving, and the development of community best practices. Preparing for the next pandemic, or simply the next seasonal epidemic, the SalivaDirect model of deploying a readily available, expandable solution and accompanying network provides a proven method for the successful implementation of pathogen testing in the United States and globally.