Trends of emergency department visits for cannabinoid hyperemesis syndrome in Nevada: An interrupted time series analysis.

Cannabis-related emergency department visits have increased after legalization of cannabis for medical and recreational use. Accordingly, the incidence of emergency department visits due to cannabinoid hyperemesis syndrome in patients with chronic cannabis use has also increased. The aim of this study was to examine trends of emergency department visit due to cannabinoid hyperemesis syndrome in Nevada and evaluate factors associated with the increased risk for emergency department visit. The State Emergency Department Databases of Nevada between 2013 and 2021 were used for investigating trends of emergency department visits for cannabinoid hyperemesis syndrome. We compared patients visiting the emergency department due to cannabinoid hyperemesis syndrome with those visiting the emergency department due to other causes except cannabinoid hyperemesis and estimated the impact of cannabis commercialization for recreational use. Emergency department visits due to cannabinoid hyperemesis syndrome have continuously increased during the study period. The number of emergency department visits per 100,000 was 1.07 before commercialization for recreational use. It increased to 2.22 per 100,000 (by approximately 1.1 per 100,000) after commercialization in the third quarter of 2017. Those with cannabinoid hyperemesis syndrome were younger with fewer male patients than those without cannabinoid hyperemesis syndrome. A substantial increase in emergency department visits due to cannabinoid hyperemesis syndrome occurred in Nevada, especially after the commercialization of recreational cannabis. Further study is needed to explore factors associated with emergency department visits.

Socioeconomic disadvantage and long-term survival duration in out-of-hospital cardiac arrest patients: A population-based cohort study.

Background: Socioeconomic status (SES) is a well-established determinant of cardiovascular health. However, the relationship between SES and clinical outcomes in long-term out-of-hospital cardiac arrest (OHCA) is less well-understood. The Singapore Housing Index (SHI) is a validated building-level SES indicator. We investigated whether SES as measured by SHI is associated with long-term OHCA survival in Singapore. Methods: We conducted an open cohort study with linked data from the Singapore Pan-Asian Resuscitation Outcomes Study (PAROS), and the Singapore Registry of Births and Deaths (SRBD) from 2010 to 2020. We fitted generalized structural equation models, calculating hazard ratios (HRs) using a Weibull model. We constructed Kaplan-Meier survival curves and calculated the predicted marginal probability for each SHI category. Results: We included 659 cases. In both univariable and multivariable analyses, SHI did not have a significant association with survival. Indirect pathways of SHI mediated through covariates such as Emergency Medical Services (EMS) response time (HR of low-medium, high-medium and high SHI when compared to low SHI: 0.98 (0.88-1.10), 1.01 (0.93-1.11), 1.02 (0.93-1.12) respectively), and age of arrest (HR of low-medium, high-medium and high SHI when compared to low SHI: 1.02 (0.75-1.38), 1.08 (0.84-1.38), 1.18 (0.91-1.54) respectively) had no significant association with OHCA survival. There was no clear trend in the predicted marginal probability of survival among the different SHI categories. Conclusions: We did not find a significant association between SES and OHCA survival outcomes in residential areas in Singapore. Among other reasons, this could be due to affordable healthcare across different socioeconomic classes.

Contributions of the Abductor Muscles to Rotational and Distractive Stability of the Hip in a Biomechanical Cadaveric Model.

Background: The gluteus minimus (GMin) and gluteus medius (GMed) are important dynamic stabilizers of the hip, but quantitative data on their biomechanical roles in stabilizing the hip are currently lacking. Purpose: To (1) establish a reproducible biomechanical cadaveric model of the hip abductor complex and (2) characterize the effects of loading the GMin and GMed on extraneous femoral rotation and distraction. Study Design: Controlled laboratory study. Methods: A total of 10 hemipelvises were tested in 4 muscle loading states: (1) unloaded, (2) the GMin loaded, (3) the GMed loaded, and (4) both the GMin and GMed loaded. Muscle loads were applied via cables, pulleys, and weights attached to the tendons to replicate the anatomic lines of action. Specimens were tested under internal rotation; external rotation; and axial traction forces at 0°, 15°, 30°, 60°, and 90° of hip flexion. Results: When loaded together, the GMin and GMed reduced internal rotation motion at all hip flexion angles (P < .05) except 60° and reduced external rotation motion at all hip flexion angles (P < .05) except 0°. Likewise, when both the GMin and GMed were loaded, femoral distraction was decreased at all angles of hip flexion (P < .05). Conclusion: The results of this study demonstrated that the GMin and GMed provide stability against rotational torques and distractive forces and that the amount of contribution depends on the degree of hip flexion. Clinical Relevance: Improved understanding of the roles of the GMin and GMed in preventing rotational and distractive instability of the hip will better guide treatment of hip pathologies and optimize nonoperative and operative therapies.

Epigenetic reprogramming shapes the cellular landscape of schwannoma.

Mechanisms specifying cancer cell states and response to therapy are incompletely understood. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas, the most common tumors of the peripheral nervous system. We find schwannomas are comprised of 2 molecular groups that are distinguished by activation of neural crest or nerve injury pathways that specify tumor cell states and the architecture of the tumor immune microenvironment. Moreover, we find radiotherapy is sufficient for interconversion of neural crest schwannomas to immune-enriched schwannomas through epigenetic and metabolic reprogramming. To define mechanisms underlying schwannoma groups, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of tumor evolution and establish a paradigm of epigenetic and metabolic reprograming of cancer cells that shapes the immune microenvironment in response to radiotherapy.

Deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial sections.

Tumors may contain billions of cells including distinct malignant clones and nonmalignant cell types. Clarifying the evolutionary histories, prevalence, and defining molecular features of these cells is essential for improving clinical outcomes, since intratumoral heterogeneity provides fuel for acquired resistance to targeted therapies. Here we present a statistically motivated strategy for deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial tumor sections (MOMA). By combining deep sampling of IDH-mutant astrocytomas with integrative analysis of single-nucleotide variants, copy-number variants, and gene expression, we reconstruct and validate the phylogenies, spatial distributions, and transcriptional profiles of distinct malignant clones. By genotyping nuclei analyzed by single-nucleus RNA-seq for truncal mutations, we further show that commonly used algorithms for identifying cancer cells from single-cell transcriptomes may be inaccurate. We also demonstrate that correlating gene expression with tumor purity in bulk samples can reveal optimal markers of malignant cells and use this approach to identify a core set of genes that is consistently expressed by astrocytoma truncal clones, including AKR1C3, whose expression is associated with poor outcomes in several types of cancer. In summary, MOMA provides a robust and flexible strategy for precisely deconstructing intratumoral heterogeneity and clarifying the core molecular properties of distinct cellular populations in solid tumors.

A road map for the treatment of pediatric diffuse midline glioma.

Recent clinical trials for H3K27-altered diffuse midline gliomas (DMGs) have shown much promise. We present a consensus roadmap and identify three major barriers: (1) refinement of experimental models to include immune and brain-specific components; (2) collaboration among researchers, clinicians, and industry to integrate patient-derived data through sharing, transparency, and regulatory considerations; and (3) streamlining clinical efforts including biopsy, CNS-drug delivery, endpoint determination, and response monitoring. We highlight the importance of comprehensive collaboration to advance the understanding, diagnostics, and therapeutics for DMGs.

The SingHealth Perioperative and Anesthesia Subject Area Registry (PASAR), a large-scale perioperative data mart and registry.

BACKGROUND: To enhance perioperative outcomes, a perioperative registry that integrates high-quality real-world data throughout the perioperative period is essential. Singapore General Hospital established the Perioperative and Anesthesia Subject Area Registry (PASAR) to unify data from the preoperative, intraoperative, and postoperative stages. This study presents the methodology employed to create this database. METHODS: Since 2016, data from surgical patients have been collected from the hospital electronic medical record systems, de-identified, and stored securely in compliance with privacy and data protection laws. As a representative sample, data from initiation in 2016 to December 2022 were collected. RESULTS: As of December 2022, PASAR data comprise 26 tables, encompassing 153,312 patient admissions and 168,977 operation sessions. For this period, the median age of the patients was 60.0 years, sex distribution was balanced, and the majority were Chinese. Hypertension and cardiovascular comorbidities were also prevalent. Information including operation type and time, intensive care unit (ICU) length of stay, and 30-day and 1-year mortality rates were collected. Emergency surgeries resulted in longer ICU stays, but shorter operation times than elective surgeries. CONCLUSIONS: The PASAR provides a comprehensive and automated approach to gathering high-quality perioperative patient data.

Navigating Love in a Post-Pandemic World: Understanding Young Adults' Views on Short- and Long-Term Romantic Relationships.

The uncertain future due to the COVID-19 pandemic and the technological advancements may have altered young adults' experiences of romantic relationships. It is unclear whether individuals will continue to prefer traditional long-term romantic relationships (LTRR) or opt for short-term ones (STRR). This research describes how young adults in Malaysia perceive LTRR and STRR. Using the structured approach of the theory of social representations, data were collected from 512 participants; 238 (46.48%) male; Mage 21.75; majority were heterosexual and students, and analyzed using prototypical analysis to reveal high consensus elements. Five observations were made: (1) females prioritize "love" in both STRR and LTRR, while males prioritize "love" only in LTRR; (2) females prioritize "marriage" in LTRR, while males prioritize "trust," "comfort," and "stability." Males do not consider "marriage" as part of a LTRR; (3) both males and females view STRR positively, while LTRR are viewed more practically; (4) "sex" is a core element in STRR but is absent in LTRR; (5) males differentiate between STRR and LTRR with no overlapping elements. These findings provide insight into the social representations of romantic relationships among young adults in Malaysia and suggest future directions for research in the field.

ChatGPT on guidelines: Providing contextual knowledge to GPT allows it to provide advice on appropriate colonoscopy intervals.

BACKGROUND AND AIM: Colonoscopy is commonly used in screening and surveillance for colorectal cancer. Multiple different guidelines provide recommendations on the interval between colonoscopies. This can be challenging for non-specialist healthcare providers to navigate. Large language models like ChatGPT are a potential tool for parsing patient histories and providing advice. However, the standard GPT model is not designed for medical use and can hallucinate. One way to overcome these challenges is to provide contextual information with medical guidelines to help the model respond accurately to queries. Our study compares the standard GPT4 against a contextualized model provided with relevant screening guidelines. We evaluated whether the models could provide correct advice for screening and surveillance intervals for colonoscopy. METHODS: Relevant guidelines pertaining to colorectal cancer screening and surveillance were formulated into a knowledge base for GPT. We tested 62 example case scenarios (three times each) on standard GPT4 and on a contextualized model with the knowledge base. RESULTS: The contextualized GPT4 model outperformed the standard GPT4 in all domains. No high-risk features were missed, and only two cases had hallucination of additional high-risk features. A correct interval to colonoscopy was provided in the majority of cases. Guidelines were appropriately cited in almost all cases. CONCLUSIONS: A contextualized GPT4 model could identify high-risk features and quote appropriate guidelines without significant hallucination. It gave a correct interval to the next colonoscopy in the majority of cases. This provides proof of concept that ChatGPT with appropriate refinement can serve as an accurate physician assistant.

Sex-specific role for the long noncoding RNA Pnky in mouse behavior.

The human brain expresses thousands of different long noncoding RNAs (lncRNAs), and aberrant expression of specific lncRNAs has been associated with cognitive and psychiatric disorders. While a growing number of lncRNAs are now known to regulate neural cell development and function, relatively few have been shown to underlie animal behavior, particularly with genetic strategies that establish lncRNA function in trans. Pnky is an evolutionarily conserved, neural lncRNA that regulates brain development. Using mouse genetic strategies, we show that Pnky has sex-specific roles in mouse behavior and that this lncRNA underlies specific behavior by functioning in trans. Male Pnky-knockout (KO) mice have deficits in cued fear recall, a type of Pavlovian associative memory. In female Pnky-KO mice, the acoustic startle response (ASR) is increased and accompanied by a decrease in prepulse inhibition (PPI), both of which are behaviors altered in affective disorders. Remarkably, expression of Pnky from a bacterial artificial chromosome (BAC) transgene reverses the ASR phenotype of female Pnky-KO mice, demonstrating that Pnky underlies specific animal behavior by functioning in trans. More broadly, these data provide genetic evidence that a lncRNA gene and its function in trans can play a key role in the behavior of adult mammals, contributing fundamental knowledge to our growing understanding of the association between specific lncRNAs and disorders of cognition and mood.

A bidirectional fabric-based soft robotic glove for hand function assistance in patients with chronic stroke.

BACKGROUND: Chronic stroke patients usually experience reduced hand functions, impeding their ability to perform activities of daily living (ADLs) independently. Additionally, improvements in hand functions by physical therapy beyond six months after the initial onset of stroke are much slower than in the earlier months. As such, chronic stroke patients could benefit from an assistive device to enhance their hand functions, allowing them to perform ADLs independently daily. In recent years, soft robotics has provided a novel approach to assistive devices for motor impaired individuals, offering more compliant and lightweight alternatives to traditional robotic devices. The scope of this study is to demonstrate the viability of a fabric-based soft robotic (SR) glove with bidirectional actuators in assisting chronic stroke study participants with hand impairments in performing ADLs. METHODS: Force and torque measurement tests were conducted to characterize the SR Glove, and hand functional tasks were given to eight chronic stroke patients to assess the efficacy of the SR Glove as an assistive device. The tasks involved object manipulation tasks that simulate ADLs, and the series of tasks was done by the participants once without assistance for baseline data, and once while using the SR Glove. A usability questionnaire was also given to each participant after the tasks were done to gain insight into how the SR Glove impacts their confidence and reliance on support while performing ADLs. RESULTS: The SR Glove improved the participants' manipulation of objects in ADL tasks. The difference in mean scores between the unassisted and assisted conditions was significant across all participants. Additionally, the usability questionnaire showed the participants felt more confident and less reliant on support while using the SR Glove to perform ADLs than without the SR Glove. CONCLUSIONS: The results from this study demonstrated that the SR Glove is a viable option to assist hand function in chronic stroke patients who suffer from hand motor impairments.

Clinical Course, Immunogenicity, and Efficacy of BNT162b2 mRNA Vaccination Against SARS-CoV-2 Infection in Liver Transplant Recipients.

Background: Immunocompromised individuals have been excluded from landmark studies of messenger RNA vaccinations for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In such patients, the response to vaccination may be blunted and may wane more quickly compared with immunocompetent patients. We studied the factors associated with decreased antibody response to SARS-CoV-2 vaccination and risk factors for subsequent breakthrough infections in liver transplant (LT) patients undergoing coronavirus disease 2019 vaccination with at least 2 doses of messenger RNA vaccine from April 28, 2021, to April 28, 2022. Methods: All LT recipients received at least 2 doses of the BNT162b2 (Pfizer BioNTech) vaccine 21 d apart. We measured the antibody response against the SARS-CoV-2 spike protein using the Roche Elecsys immunoassay to the receptor-binding domain of the SARS-CoV-2 spike protein, and the presence of neutralizing antibodies was measured by the surrogate virus neutralization test (cPass) before first and second doses of vaccination and also between 2 and 3 mo after the second dose of vaccination. Results: Ninety-three LT recipients who received 2 doses of BNT162b2 were included in the analysis. The mean time from LT was 110 ± 154 mo. After 2-dose vaccination, 38.7% of LT recipients (36/93) were vaccine nonresponders on the cPass assay compared with 20.4% (19/93) on the Roche S assay. On multivariable analysis, increased age and increased tacrolimus trough were found to be associated with poor neutralizing antibody response (P = 0.038 and 0.022, respectively). The use of antimetabolite therapy in conjunction with tacrolimus approached statistical significance (odds ratio 0.21; 95% confidence interval, 0.180-3.72; P = 0.062). Breakthrough infection occurred in 18 of 88 LT recipients (20.4%). Female gender was independently associated with breakthrough infections (P < 0.001). Conclusions: Among LT recipients, older age and higher tacrolimus trough levels were associated with poorer immune response to 2-dose SARS-CoV-2 vaccination. Further studies are needed to assess variables associated with breakthrough infections and, hence, who should be prioritized for booster vaccination.

Desmoplastic Fibroma of the Mandible: A Case Without Recurrence After Enucleation.

Desmoplastic fibroma (DF) is a rare, benign, yet locally aggressive bone tumor. It frequently affects the facial bones, and the mandible is the most commonly affected site. Treatment of choice is the removal of the tumor with resection of surrounding bone due to its aggressive behavior. We report a case of DF where the tumor showed resolution and almost complete bone deposition following enucleation. Although DF has a high recurrence rate, the patient remains disease-free 31 months post-surgery.

Performance of the ROX index in predicting high flow nasal cannula failure in COVID-19 patients: a systematic review and meta-analysis.

COVID-19 patients with acute hypoxemic respiratory failure (AHRF) benefit from high flow nasal cannula (HFNC) oxygen therapy. However, delays in initiating invasive ventilation after HFNC failure are associated with poorer outcomes. The respiratory oxygenation (ROX) index, combining SpO2/FiO2 and respiratory rate, can predict HFNC failure. This meta-analysis evaluated the optimal ROX index cut-offs in predicting HFNC failure among COVID-19 patients at different measurement timings and clinical settings. Three databases were searched for eligible papers. From each study, we reconstructed the confusion matrices at different cut-offs, fitted linear mixed models to estimate the ROX index distribution function, and derived the area under the summary receiver operator characteristic curve (sAUC) and optimal cut-offs to predict HFNC failure. 24 studies containing 4790 patients were included. Overall sAUC was 0.771 (95% CI: 0.666-0.847) (optimal cut-off: 5.23, sensitivity: 0.732, specificity: 0.690). The cut-off values to achieve 80%, 90% sensitivity, 80%, 90% specificity were 5.70, 6.69, 4.45, 3.37, respectively. We stratified the analysis by ROX measurement time and estimated optimal cut-offs and cut-offs to achieve 80% sensitivity and specificity. For 2-6 h and 6-12 h post-HFNC initiation, we propose the use of 80% specific cut-offs to rule in HFNC failure of < 5.33 and < 3.69, respectively. For 12-24 h post-HFNC initiation, we propose the use of the 80% sensitive cut-off of > 6.07 to rule out HFNC failure. Our analysis confirms the overall utility of the ROX index in risk stratification of COVID-19 patients with AHRF receiving HFNC and provides potentially useful cut-offs for different times from HFNC initiation.

Outcomes of Investigating T Wave Inversion With Echocardiography in an Unselected Young Male Preparticipation Cohort.

BACKGROUND Electrocardiography (ECG) may be performed as part of preparticipation sports screening. Recommendations on screening of athletes to identify individuals with previously unrecognized cardiac disease are robust; however, data guiding the preparticipation screening of unselected populations are scarce. T wave inversion (TWI) on ECG may suggest an undiagnosed cardiomyopathy. This study aims to describe the prevalence of abnormal TWI in an unselected young male cohort and the outcomes of an echocardiography-guided approach to investigating these individuals for structural heart diseases, focusing on the yield for cardiomyopathies. METHODS AND RESULTS Consecutive young male individuals undergoing a national preparticipation cardiac screening program for 39 months were studied. All underwent resting supine 12-lead ECG. Those manifesting abnormal TWI, defined as negatively deflected T waves of at least 0.1 mV amplitude in any 2 contiguous leads, underwent echocardiography. A total of 69 714 male individuals with a mean age of 17.9±1.1 years were studied. Of the individuals, 562 (0.8%) displayed abnormal TWI. This was most frequently observed in the anterior territory and least so in the lateral territory. A total of 12 individuals (2.1%) were diagnosed with a cardiomyopathy. Cardiomyopathy diagnoses were significantly associated with deeper maximum TWI depth and the presence of abnormal TWI in the lateral territory, but not with abnormal TWI in the anterior and inferior territories. No individual presenting with TWI restricted to solely leads V1 to V2, 2 inferior leads or both was diagnosed with a cardiomyopathy. CONCLUSIONS Cardiomyopathy diagnoses were more strongly associated with certain patterns of abnormal TWI. Our findings may support decisions to prioritize echocardiography in these individuals.