Unintentional ingestion of putative delta-8 tetrahydrocannabinol by two youth requiring critical care: a case report.

BACKGROUND: Delta-8 tetrahydrocannabinol (THC) is a psychoactive cannabinoid from the cannabis plant that can be synthetically converted from cannabidiol (CBD). Most states permit the full or restricted sale of hemp and hemp-derived CBD products, and therefore, delta-8 THC products are on the rise. Delta-8 THC consumption can cause intoxication. Products are often sold in edible form and occasionally in packaging that appears similar to candy. Clinical presentations for delta-8 THC ingestions are understudied and may differ from those described for delta-9 THC ingestions. CASE PRESENTATION: This case report describes unintentional ingestions of putative delta-8 THC by two pediatric patients that results in admission to the pediatric intensive care unit. The ingestions were of putative delta-8 THC infused product that resembled popular candies. Both patients developed periods of bradypnea with continued intermittent periods of agitation. Medical intervention included observation, noninvasive positive pressure ventilation via high flow nasal cannula, and intubation-but was not needed for both patients. Although family noted ongoing irritability for the patients, both were discharged approximately 45 h after ingestion. Delta-8 THC ingestion is reliant on self-report. CONCLUSIONS: As the availability of delta-8 THC increases, along with associated pediatric exposures, it is imperative for health care providers to quickly recognize and provide adequate treatment. While there is no specific antidote for THC intoxication beyond supportive care, providers can play an important role in prevention by educating parents and guardians on safe cannabis storage and by documenting cases for adverse event monitoring.

Experiences with Medications for Addiction Treatment Among Emergency Department Patients with Opioid Use Disorder.

INTRODUCTION: Medications for addiction treatment (MAT) are the evidence-based standard of care for treatment of opioid use disorder (OUD), but stigma continues to surround their use. We conducted an exploratory study to characterize perceptions of different types of MAT among people who use drugs. METHODS: We conducted this qualitative study in adults with a history of non-medical opioid use who presented to an emergency department for complications of OUD. A semi-structured interview that explored knowledge, perceptions, and attitudes toward MAT was administered, and applied thematic analysis conducted. RESULTS: We enrolled 20 adults. All participants had prior experience with MAT. Among participants indicating a preferred treatment modality, buprenorphine was the commonly favored agent. Previous experience with prolonged withdrawal symptoms upon MAT discontinuation and the perception of "trading one drug for another" were common reasons for reluctance to engage in agonist or partial-agonist therapy. While some participants preferred treatment with naltrexone, others were unwilling to initiate antagonist therapy due to fear of precipitated withdrawal. Most participants strongly considered the aversive nature of MAT discontinuation as a barrier to initiating treatment. Participants overall viewed MAT positively, but many had strong preferences for a particular agent. CONCLUSION: The anticipation of withdrawal symptoms during initiation and cessation of treatment affected willingness to engage in a specific therapy. Future educational materials for people who use drugs may focus on comparisons of respective benefits and drawbacks of agonists, partial agonists, and antagonists. Emergency clinicians must be prepared to answer questions about MAT discontinuation to effectively engage patients with OUD.

Oropharyngeal microbiome profiled at admission is predictive of the need for respiratory support among COVID-19 patients.

The oropharyngeal microbiome, the collective genomes of the community of microorganisms that colonizes the upper respiratory tract, is thought to influence the clinical course of infection by respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Infectious Disease 2019 (COVID-19). In this study, we examined the oropharyngeal microbiome of suspected COVID-19 patients presenting to the Emergency Department and an inpatient COVID-19 unit with symptoms of acute COVID-19. Of 115 initially enrolled patients, 50 had positive molecular testing for COVID-19+ and had symptom duration of 14 days or less. These patients were analyzed further as progression of disease could most likely be attributed to acute COVID-19 and less likely a secondary process. Of these, 38 (76%) went on to require some form of supplemental oxygen support. To identify functional patterns associated with respiratory illness requiring respiratory support, we applied an interpretable random forest classification machine learning pipeline to shotgun metagenomic sequencing data and select clinical covariates. When combined with clinical factors, both species and metabolic pathways abundance-based models were found to be highly predictive of the need for respiratory support (F1-score 0.857 for microbes and 0.821 for functional pathways). To determine biologically meaningful and highly predictive signals in the microbiome, we applied the Stable and Interpretable RUle Set to the output of the models. This analysis revealed that low abundance of two commensal organisms, Prevotella salivae or Veillonella infantium (< 4.2 and 1.7% respectively), and a low abundance of a pathway associated with LPS biosynthesis (< 0.1%) were highly predictive of developing the need for acute respiratory support (82 and 91.4% respectively). These findings suggest that the composition of the oropharyngeal microbiome in COVID-19 patients may play a role in determining who will suffer from severe disease manifestations.

Oropharyngeal Microbiome Profiled at Admission is Predictive of the Need for Respiratory Support Among COVID-19 Patients.

The clinical course of infection due to respiratory viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), the causative agent of Coronavirus Disease 2019 (COVID-19) is thought to be influenced by the community of organisms that colonizes the upper respiratory tract, the oropharyngeal microbiome. In this study, we examined the oropharyngeal microbiome of suspected COVID-19 patients presenting to the Emergency Department and an inpatient COVID-19 unit with symptoms of acute COVID-19. Of 115 enrolled patients, 74 were confirmed COVID-19+ and 50 had symptom duration of 14 days or less; 38 acute COVID-19+ patients (76%) went on to require respiratory support. Although no microbiome features were found to be significantly different between COVID-19+ and COVID-19-patients, when we conducted random forest classification modeling (RFC) to predict the need of respiratory support for the COVID-19+ patients our analysis identified a subset of organisms and metabolic pathways whose relative abundance, when combined with clinical factors (such as age and Body Mass Index), was highly predictive of the need for respiratory support (F1 score 0.857). Microbiome Multivariable Association with Linear Models (MaAsLin2) analysis was then applied to the features identified as predicative of the need for respiratory support by the RFC. This analysis revealed reduced abundance of Prevotella salivae and metabolic pathways associated with lipopolysaccharide and mycolic acid biosynthesis to be the strongest predictors of patients requiring respiratory support. These findings suggest that composition of the oropharyngeal microbiome in COVID-19 may play a role in determining who will suffer from severe disease manifestations. Importance: The microbial community that colonizes the upper airway, the oropharyngeal microbiome, has the potential to affect how patients respond to respiratory viruses such as SARS-CoV2, the causative agent of COVID-19. In this study, we investigated the oropharyngeal microbiome of COVID-19 patients using high throughput DNA sequencing performed on oral swabs. We combined patient characteristics available at intake such as medical comorbidities and age, with measured abundance of bacterial species and metabolic pathways and then trained a machine learning model to determine what features are predicative of patients needing respiratory support in the form of supplemental oxygen or mechanical ventilation. We found that decreased abundance of some bacterial species and increased abundance of pathways associated bacterial products biosynthesis was highly predictive of needing respiratory support. This suggests that the oropharyngeal microbiome affects disease course in COVID-19 and could be targeted for diagnostic purposes to determine who may need oxygen, or therapeutic purposes such as probiotics to prevent severe COVID-19 disease manifestations.

The Urinary Microbiome of Older Adults Residing in a Nursing Home Varies With Duration of Residence and Shows Increases in Potential Pathogens.

The community of bacteria that colonize the urinary tract, the urinary microbiome, is hypothesized to influence a wide variety of urinary tract conditions. Older adults who reside in nursing homes are frequently diagnosed and treated for urinary tract conditions such as urinary tract infection. We investigated the urinary microbiome of older adults residing in a nursing home to determine if there are features of the urinary microbiome that are associated with specific conditions and exposure in this population. We were also interested in the stability of urinary microbiome over time and in similarities between the urinary and gastrointestinal microbiome. Urine samples were prospectively collected over a period of 10 months from a cohort of 26 older adults (aged >65 years) residing in a single nursing home located in Central Massachusetts. Serial samples were obtained from 6 individuals over 10 months and 5 participants were concurrently enrolled in a study of the gastrointestinal microbiome. Information collected on participants included demographics, medical history, duration of residence in the nursing home, frailty, dementia symptoms, urinary symptoms, antibiotic treatment, urinary catheterization, and hospitalizations over a 10-month period. Clean catch, midstream urine samples were collected and stored at -80°C. DNA was extracted and 16S rRNA gene sequencing was performed. The length of stay in the nursing facility and the Clinical Frailty Scale correlated with significant changes in microbiome composition. An increase in the relative abundance of a putative urinary pathogen, Aerococcus urinae, was the largest factor influencing change that occurred over the duration of residence.

A genome-wide approach to discovery of small RNAs involved in regulation of virulence in Vibrio cholerae.

Small RNAs (sRNAs) are becoming increasingly recognized as important regulators in bacteria. To investigate the contribution of sRNA mediated regulation to virulence in Vibrio cholerae, we performed high throughput sequencing of cDNA generated from sRNA transcripts isolated from a strain ectopically expressing ToxT, the major transcriptional regulator within the virulence gene regulon. We compared this data set with ToxT binding sites determined by pulldown and deep sequencing to identify sRNA promoters directly controlled by ToxT. Analysis of the resulting transcripts with ToxT binding sites in cis revealed two sRNAs within the Vibrio Pathogenicity Island. When deletions of these sRNAs were made and the resulting strains were competed against the parental strain in the infant mouse model of V. cholerae colonization, one, TarB, displayed a variable colonization phenotype dependent on its physiological state at the time of inoculation. We identified a target of TarB as the mRNA for the secreted colonization factor, TcpF. We verified negative regulation of TcpF expression by TarB and, using point mutations that disrupted interaction between TarB and tpcF mRNA, showed that loss of this negative regulation was primarily responsible for the colonization phenotype observed in the TarB deletion mutant.

Costimulation via OX40L expressed by B cells is sufficient to determine the extent of primary CD4 cell expansion and Th2 cytokine secretion in vivo.

The development of effector and memory CD4 cell populations depends upon both T cell receptor (TCR) engagement of peptide/major histocompatibility complex (MHC) class II complexes and ligation of costimulatory molecules with counter receptors on antigen-presenting cells (APCs). We showed previously that sustained interactions with APCs could be crucial for optimal expansion of CD4 cells and for development of effectors that secrete cytokines associated with Th2 cells. Using an adoptive transfer model with TCR transgenic CD4 cells, we now show that responses of CD4 cells primed in B cell-deficient mice become aborted, but are fully restored upon the transfer of activated B cells. Although B cells have the capacity to secrete multiple cytokines that could affect CD4 priming, including IL-4, we were unable to distinguish a role for cytokines that are secreted by B cells. However, B cell costimulation via the OX40L/OX40 pathway that has been implicated in CD4 cell expansion, survival, and Th2 development was required. Th2 but not Th1 responses were impaired in OX40L-deficient recipients and normal responses were restored with OX40L sufficient B cells. The results suggest that without engagement of OX40L on B cells, CD4 cell responses to many protein Ag would be dominated by Th1 cytokines. These data have important implications for strategies to achieve optimal priming of CD4 subsets.