Cannabidiol promotes intestinal cholesterol uptake mediated by Pregnane X receptor.

Background: Cannabidiol (CBD), a non-psychoactive phytocannabinoid of cannabis, is therapeutically used as an analgesic, anti-convulsant, anti-inflammatory, and anti-psychotic drug. There is a growing concern about the adverse side effects posed by CBD usage. Pregnane X receptor (PXR) is a nuclear receptor activated by a variety of dietary steroids, pharmaceutical agents, and environmental chemicals. In addition to the role in xenobiotic metabolism, the atherogenic and dyslipidemic effects of PXR have been revealed in animal models. CBD has a low affinity for cannabinoid receptors, thus it is important to elucidate the molecular mechanisms by which CBD activates cellular signaling and to assess the possible adverse impacts of CBD on pro-atherosclerotic events in cardiovascular system, such as dyslipidemia. Objective: Our study aims to explore the cellular and molecular mechanisms by which exposure to CBD activates human PXR and increases the risk of dyslipidemia. Methods: Both human hepatic and intestinal cells were used to test if CBD was a PXR agonist via cell-based transfection assay. The key residues within PXR's ligand-binding pocket that CBD interacted with were investigated using computational docking study together with site-directed mutagenesis assay. The C57BL/6 wildtype mice were orally fed CBD in the presence of PXR antagonist resveratrol (RES) to determine how CBD exposure could change the plasma lipid profiles in a PXR-dependent manner. Human intestinal cells were treated with CBD and/or RES to estimate the functions of CBD in cholesterol uptake. Results: CBD was a selective agonist of PXR with higher activities on human PXR than rodents PXRs and promoted the dissociation of human PXR from nuclear co-repressors. The key amino acid residues Met246, Ser247, Phe251, Phe288, Trp299, and Tyr306 within PXR's ligand binding pocket were identified to be necessary for the agonistic effects of CBD. Exposure to CBD increased the circulating total cholesterol levels in mice which was partially caused by the induced expression levels of the key intestinal PXR-regulated lipogenic genes. Mechanistically, CBD induced the gene expression of key intestinal cholesterol transporters, which led to the increased cholesterol uptake by intestinal cells. Conclusion: CBD was identified as a selective PXR agonist. Exposure to CBD activated PXR signaling and increased the atherogenic cholesterol levels in plasma, which partially resulted from the ascended cholesterol uptake by intestinal cells. Our study provides potential evidence for the future risk assessment of CBD on cardiovascular disease, such as dyslipidemia.

Evaluation of a Large Language Model to Identify Confidential Content in Adolescent Encounter Notes.

This cross-sectional study assesses the ability of a language learning model to classify whether a progress note contains confidential information and to identify the specific confidential content in the note.

Infections After Adoption of Antibiogram-directed Prophylaxis and Intracorporeal Urinary Diversion for Robot-assisted Radical Cystectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) has significantly decreased the morbidity associated with radical cystectomy. However, infectious complications including sepsis, urinary tract (UTIs), wound (WIs), and intra-abdominal (AIs) infections remain common. OBJECTIVE: To assess whether intracorporeal urinary diversion (ICUD) and antibiogram-directed antimicrobial prophylaxis would decrease infections after robotic-assisted radical cystectomy (RARC). DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was performed of a prospectively maintained database of patients undergoing RARC between 2014 and 2022 at a tertiary care institution, identifying two groups based on adherence to a prospectively implemented modified ERAS protocol for RARC: modified-ERAS-ICUD and antibiogram-directed ampicillin-sulbactam, gentamicin, and fluconazole prophylaxis were utilized (from January 2019 to present time), and unmodified-ERAS-extracorporeal urinary diversion (UD) and guideline-recommended cephalosporin-based prophylaxis regimen were utilized (from November 2014 to June 2018). Patients receiving other prophylaxis regimens were excluded. INTERVENTION: ICUD and antibiogram-directed infectious prophylaxis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was UTIs within 30 and 90 d postoperatively. The secondary outcomes were WIs, AIs, and sepsis within 30 and 90 d postoperatively, and Clostridioides difficile infection (CDI) within 90 d postoperatively. RESULTS AND LIMITATIONS: A total of 396 patients were studied (modified-ERAS: 258 [65.2%], unmodified-ERAS: 138 [34.8%]). UD via a neobladder was more common in the modified-ERAS cohort; all other intercohort demographic differences were not statistically different. Comparing cohorts, modified-ERAS had significantly reduced rates of 30-d (7.8% vs 15.9%, p = 0.027) and 90-d UTIs (11.2% vs 25.4%, p = 0.001), and 30-d WIs (1.2% vs. 8.7%, p < 0.001); neither group had a WI after 30 d. Rates of AIs, sepsis, and CDI did not differ between groups. On multivariate regression, the modified-ERAS protocol correlated with a reduced risk of UTIs and WIs (all p < 0.01). The primary limitation is the retrospective study design. CONCLUSIONS: Utilization of ICUD and antibiogram-based prophylaxis correlates with significantly decreased UTIs and WIs after RARC. PATIENT SUMMARY: In this study of infections after robotic radical cystectomy for bladder cancer, we found that intracorporeal (performed entirely inside the body) urinary diversion and an institution-specific antibiogram-directed antibiotic prophylaxis regimen led to fewer urinary tract infections and wound infections at our institution.

The Prevalence of Confidential Content in Adolescent Progress Notes Prior to the 21st Century Cures Act Information Blocking Mandate.

BACKGROUND: The 21st Century Cures Act information blocking final rule mandated the immediate and electronic release of health care data in 2020. There is anecdotal concern that a significant amount of information is documented in notes that would breach adolescent confidentiality if released electronically to a guardian. OBJECTIVES: The purpose of this study was to quantify the prevalence of confidential information, based on California laws, within progress notes for adolescent patients that would be released electronically and assess differences in prevalence across patient demographics. METHODS: This is a single-center retrospective chart review of outpatient progress notes written between January 1, 2016, and December 31, 2019, at a large suburban academic pediatric network. Notes were labeled into one of three confidential domains by five expert reviewers trained on a rubric defining confidential information for adolescents derived from California state law. Participants included a random sampling of eligible patients aged 12 to 17 years old at the time of note creation. Secondary analysis included prevalence of confidentiality across age, gender, language spoken, and patient race. RESULTS: Of 1,200 manually reviewed notes, 255 notes (21.3%) (95% confidence interval: 19-24%) contained confidential information. There was a similar distribution among gender and age and a majority of English speaking (83.9%) and white or Caucasian patients (41.2%) in the cohort. Confidential information was more likely to be found in notes for females (p < 0.05) as well as for English-speaking patients (p < 0.05). Older patients had a higher probability of notes containing confidential information (p < 0.05). CONCLUSION: This study demonstrates that there is a significant risk to breach adolescent confidentiality if historical progress notes are released electronically to proxies without further review or redaction. With increased sharing of health care data, there is a need to protect the privacy of the adolescents and prevent potential breaches of confidentiality.

A Natural Language Processing Model to Identify Confidential Content in Adolescent Clinical Notes.

BACKGROUND: The 21st Century Cures Act mandates the immediate, electronic release of health information to patients. However, in the case of adolescents, special consideration is required to ensure that confidentiality is maintained. The detection of confidential content in clinical notes may support operational efforts to preserve adolescent confidentiality while implementing information sharing. OBJECTIVES: This study aimed to determine if a natural language processing (NLP) algorithm can identify confidential content in adolescent clinical progress notes. METHODS: A total of 1,200 outpatient adolescent progress notes written between 2016 and 2019 were manually annotated to identify confidential content. Labeled sentences from this corpus were featurized and used to train a two-part logistic regression model, which provides both sentence-level and note-level probability estimates that a given text contains confidential content. This model was prospectively validated on a set of 240 progress notes written in May 2022. It was subsequently deployed in a pilot intervention to augment an ongoing operational effort to identify confidential content in progress notes. Note-level probability estimates were used to triage notes for review and sentence-level probability estimates were used to highlight high-risk portions of those notes to aid the manual reviewer. RESULTS: The prevalence of notes containing confidential content was 21% (255/1,200) and 22% (53/240) in the train/test and validation cohorts, respectively. The ensemble logistic regression model achieved an area under the receiver operating characteristic of 90 and 88% in the test and validation cohorts, respectively. Its use in a pilot intervention identified outlier documentation practices and demonstrated efficiency gains over completely manual note review. CONCLUSION: An NLP algorithm can identify confidential content in progress notes with high accuracy. Its human-in-the-loop deployment in clinical operations augmented an ongoing operational effort to identify confidential content in adolescent progress notes. These findings suggest NLP may be used to support efforts to preserve adolescent confidentiality in the wake of the information blocking mandate.

Monitoring Approaches for a Pediatric Chronic Kidney Disease Machine Learning Model.

OBJECTIVE: The purpose of this study is to evaluate the ability of three metrics to monitor for a reduction in performance of a chronic kidney disease (CKD) model deployed at a pediatric hospital. METHODS: The CKD risk model estimates a patient's risk of developing CKD 3 to 12 months following an inpatient admission. The model was developed on a retrospective dataset of 4,879 admissions from 2014 to 2018, then run silently on 1,270 admissions from April to October, 2019. Three metrics were used to monitor its performance during the silent phase: (1) standardized mean differences (SMDs); (2) performance of a "membership model"; and (3) response distribution analysis. Observed patient outcomes for the 1,270 admissions were used to calculate prospective model performance and the ability of the three metrics to detect performance changes. RESULTS: The deployed model had an area under the receiver-operator curve (AUROC) of 0.63 in the prospective evaluation, which was a significant decrease from an AUROC of 0.76 on retrospective data (p = 0.033). Among the three metrics, SMDs were significantly different for 66/75 (88%) of the model's input variables (p <0.05) between retrospective and deployment data. The membership model was able to discriminate between the two settings (AUROC = 0.71, p <0.0001) and the response distributions were significantly different (p <0.0001) for the two settings. CONCLUSION: This study suggests that the three metrics examined could provide early indication of performance deterioration in deployed models' performance.

Adding glycemic and physical activity metrics to a multimodal algorithm-enabled decision-support tool for type 1 diabetes care: Keys to implementation and opportunities.

Algorithm-enabled patient prioritization and remote patient monitoring (RPM) have been used to improve clinical workflows at Stanford and have been associated with improved glucose time-in-range in newly diagnosed youth with type 1 diabetes (T1D). This novel algorithm-enabled care model currently integrates continuous glucose monitoring (CGM) data to prioritize patients for weekly reviews by the clinical diabetes team. The use of additional data may help clinical teams make more informed decisions around T1D management. Regular exercise and physical activity are essential to increasing cardiovascular fitness, increasing insulin sensitivity, and improving overall well-being of youth and adults with T1D. However, exercise can lead to fluctuations in glycemia during and after the activity. Future iterations of the care model will integrate physical activity metrics (e.g., heart rate and step count) and physical activity flags to help identify patients whose needs are not fully captured by CGM data. Our aim is to help healthcare professionals improve patient care with a better integration of CGM and physical activity data. We hypothesize that incorporating exercise data into the current CGM-based care model will produce specific, clinically relevant information such as identifying whether patients are meeting exercise guidelines. This work provides an overview of the essential steps of integrating exercise data into an RPM program and the most promising opportunities for the use of these data.

Modern best practice in the management of benign prostatic hyperplasia in the elderly.

Benign prostatic hyperplasia (BPH), with its associated lower urinary tract symptoms (LUTS), can be a debilitating disease in the elderly male. Transurethral resection of the prostate (TURP) remains the gold standard; however, many patients will choose to avoid surgery if possible. Medical therapy is an effective alternative, however, new studies are showing that there may be more side effects than previously realized in the elderly male. Newer, novel minimally invasive techniques, including UroLift® and Rezum™, are gaining favor as alternative office-based procedural techniques that do not require general anesthesia and may better preserve ejaculatory function. Though promising, at this point, these techniques are not approved for all patients. With a range of medical, procedural, and surgical options for treatment of BPH with LUTS, it is important to have a discussion with your patient regarding the short- and long-term risks and benefits, as well as alternatives, before deciding on a treatment plan for your patient with BPH.

Tales of diversity: Genomic and morphological characteristics of forty-six Arthrobacter phages.

The vast bacteriophage population harbors an immense reservoir of genetic information. Almost 2000 phage genomes have been sequenced from phages infecting hosts in the phylum Actinobacteria, and analysis of these genomes reveals substantial diversity, pervasive mosaicism, and novel mechanisms for phage replication and lysogeny. Here, we describe the isolation and genomic characterization of 46 phages from environmental samples at various geographic locations in the U.S. infecting a single Arthrobacter sp. strain. These phages include representatives of all three virion morphologies, and Jasmine is the first sequenced podovirus of an actinobacterial host. The phages also span considerable sequence diversity, and can be grouped into 10 clusters according to their nucleotide diversity, and two singletons each with no close relatives. However, the clusters/singletons appear to be genomically well separated from each other, and relatively few genes are shared between clusters. Genome size varies from among the smallest of siphoviral phages (15,319 bp) to over 70 kbp, and G+C contents range from 45-68%, compared to 63.4% for the host genome. Although temperate phages are common among other actinobacterial hosts, these Arthrobacter phages are primarily lytic, and only the singleton Galaxy is likely temperate.