Delirium detection in the emergency department: A diagnostic accuracy meta-analysis of history, physical examination, laboratory tests, and screening instruments.

INTRODUCTION: Geriatric emergency department (ED) guidelines emphasize timely identification of delirium. This article updates previous diagnostic accuracy systematic reviews of history, physical examination, laboratory testing, and ED screening instruments for the diagnosis of delirium as well as test-treatment thresholds for ED delirium screening. METHODS: We conducted a systematic review to quantify the diagnostic accuracy of approaches to identify delirium. Studies were included if they described adults aged 60 or older evaluated in the ED setting with an index test for delirium compared with an acceptable criterion standard for delirium. Data were extracted and studies were reviewed for risk of bias. When appropriate, we conducted a meta-analysis and estimated delirium screening thresholds. RESULTS: Full-text review was performed on 55 studies and 27 were included in the current analysis. No studies were identified exploring the accuracy of findings on history or laboratory analysis. While two studies reported clinicians accurately rule in delirium, clinician gestalt is inadequate to rule out delirium. We report meta-analysis on three studies that quantified the accuracy of the 4 A's Test (4AT) to rule in (pooled positive likelihood ratio [LR+] 7.5, 95% confidence interval [CI] 2.7-20.7) and rule out (pooled negative likelihood ratio [LR-] 0.18, 95% CI 0.09-0.34) delirium. We also conducted meta-analysis of two studies that quantified the accuracy of the Abbreviated Mental Test-4 (AMT-4) and found that the pooled LR+ (4.3, 95% CI 2.4-7.8) was lower than that observed for the 4AT, but the pooled LR- (0.22, 95% CI 0.05-1) was similar. Based on one study the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is the superior instrument to rule in delirium. The calculated test threshold is 2% and the treatment threshold is 11%. CONCLUSIONS: The quantitative accuracy of history and physical examination to identify ED delirium is virtually unexplored. The 4AT has the largest quantity of ED-based research. Other screening instruments may more accurately rule in or rule out delirium. If the goal is to rule in delirium then the CAM-ICU or brief CAM or modified CAM for the ED are superior instruments, although the accuracy of these screening tools are based on single-center studies. To rule out delirium, the Delirium Triage Screen is superior based on one single-center study.

Behavioral therapies targeting reward mechanisms in substance use disorders.

Behavioral therapies are considered best practices in the treatment of substance use disorders (SUD) and used as first-line approaches for SUDs without FDA-approved pharmacotherapies. Decades of research on the neuroscience of drug reward and addiction have informed the development of current leading behavioral therapies that, while differing in focus and technique, have in common the overarching goal of shifting reward responding away from drug and toward natural non-drug rewards. This review begins by describing key neurobiological processes of reward in addiction, followed by a description of how various behavioral therapies address specific reward processes. Based on this review, a conceptual 'map' is crafted to pinpoint gaps and areas of overlap, serving as a guide for selecting and integrating behavioral therapies.

Opioid Risk Tool, in-hospital opioid exposure, and opioid demand predict pain outcomes following traumatic injury.

Prescribed opioids are a mainstay pain treatment after traumatic injury, but a subgroup of patients may be at risk for continued opioid use. We evaluated the predictive utility of a traditional screening tool, the Opioid Risk Tool (ORT), and two other measures: average in-hospital milligram morphine equivalents (MME) per day and an assessment of opioid demand in predicting pain outcomes. Assessments of pain-related outcomes (pain intensity, interference, injury-related stress, and need for additional pain treatment) were administered at 2 weeks and 12 months post-discharge in a sample of 34 patients hospitalized for traumatic injury. Bayesian linear models were used to evaluate changes in responses over time as a function of predictors. High-risk ORT, higher MME per day, and greater opioid demand predicted less change in outcomes over time. This report provides first evidence that malleable factors of opioid and opioid demand have utility in predicting pain outcomes following traumatic injury.

Analysis of patient safety event report categories at one large academic hospital.

Given the persistent safety incidents in operating rooms (ORs) nationwide (approx. 4,000 preventable harmful surgical errors per year), there is a need to better analyze and understand reported patient safety events. This study describes the results of applying the Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) supported by the Teamwork Evaluation of Non-Technical Skills (TENTS) instrument to analyze patient safety event reports at one large academic medical center. Results suggest that suboptimal behaviors stemming from poor communication, lack of situation monitoring, and inappropriate task prioritization and execution were implicated in most reported events. Our proposed methodology offers an effective way of programmatically sorting and prioritizing patient safety improvement efforts.

Cost-effectiveness of early intervention in psychosis in low- and middle-income countries: economic evaluation from São Paulo, Brazil.

AIMS: The effectiveness and cost-effectiveness of early intervention for psychosis (EIP) services are well established in high-income countries but not in low- and middle-income countries (LMICs). Despite the scarcity of local evidence, several EIP services have been implemented in LMICs. Local evaluations are warranted before adopting speciality models of care in LMICs. We aimed to estimate the cost-effectiveness of implementing EIP services in Brazil. METHODS: A model-based economic evaluation of EIP services was conducted from the Brazilian healthcare system perspective. A Markov model was developed using a cohort study conducted in São Paulo. Cost data were retrieved from local sources. The outcome of interest was the incremental cost-effectiveness ratio (ICER) measured as the incremental costs over the incremental quality-adjusted life-years (QALYs). Sensitivity analyses were performed to test the robustness of the results. RESULTS: The study included 357 participants (38% female), with a mean (SD) age of 26 (7.38) years. According to the model, implementing EIP services in Brazil would result in a mean incremental cost of 4,478 Brazilian reals (R$) and a mean incremental benefit of 0.29 QALYs. The resulting ICER of R$ 15,495 (US dollar [USD] 7,640 adjusted for purchase power parity [PPP]) per QALY can be considered cost-effective at a willingness-to-pay threshold of 1 Gross domestic product (GDP) per capita (R$ 18,254; USD 9,000 PPP adjusted). The model results were robust to sensitivity analyses. CONCLUSIONS: This study supports the economic advantages of implementing EIP services in Brazil. Although cultural adaptations are required, these data suggest EIP services might be cost-effective even in less-resourced countries.

An Acid-Responsive Iron-Based Nanocomposite for OSCC Treatment.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, characterized by invasiveness, local lymph node metastasis, and poor prognosis. Traditional treatment and medications have limitations, making the specific inhibition of OSCC growth, invasion, and metastasis a challenge. The tumor microenvironment exhibits mildly acidity and high concentrations of H2O2, and its exploitation for cancer treatment has been widely researched across various cancers, but research in the oral cancer field is relatively limited. In this study, by loading ultra-small Prussian blue nanoparticles (USPBNPs) into mesoporous calcium-silicate nanoparticles (MCSNs), we developed an acid-responsive iron-based nanocomposite, USPBNPs@MCSNs (UPM), for the OSCC treatment. UPM demonstrated excellent dual enzyme activities, generating toxic ·OH in a mildly acidic environment, effectively killing OSCC cells and producing O2 in a neutral environment to alleviate tissue hypoxia. The results showed that UPM could effectively inhibit the proliferation, migration, and invasion of OSCC cells, as well as the growth of mice solid tumors, without obvious systemic toxicity. The mechanisms may involve UPM inducing ferroptosis of OSCC cells by downregulating the xCT/GPX4/glutathione (GSH) axis, characterized by intracellular iron accumulation, reactive oxygen species accumulation, GSH depletion, lipid peroxidation, and abnormal changes in mitochondrial morphology. Therefore, this study provides empirical support for ferroptosis as an emerging therapeutic target for OSCC and offers a valuable insight for future OSCC treatment.

Nightly Sleep Predicts Next-Morning Expectations for Stress and Positive Experiences.

OBJECTIVE: Abundant research has linked nightly sleep as an antecedent of daily psychosocial experiences; however, less is known about sleep's influence on daily expectations of these experiences. Therefore, this research examined the day-to-day associations of sleep quality, duration, and efficiency with next-day expectations for stress(ors) and positive experiences, as well as whether these expectations were related to end-of-day reports of physical symptoms. METHODS: In Study 1, U.S. adults ( n = 354; ages 19 to 74) completed twice-daily diaries for 10 weekdays about sleep, expectations for encountering daily stressors and positive events, and physical symptoms. In Study 2, adults in Canada ( n = 246; ages 25 to 87) wore a sleep watch for 14 consecutive days and completed mobile surveys 5×/day about sleep, stressfulness and pleasantness expectations, and physical symptoms. RESULTS: Multilevel models indicated that self-reported sleep quality and duration, but not efficiency, were associated with lower next-day expectations for stressors (Study 1) and stressfulness (Study 2). Self-reported sleep quality (Study 1) and all sleep indices (Study 2) predicted greater next-day expectations for positive events and pleasantness, respectively. For actigraphy-assessed sleep (Study 2), only longer-than-usual actigraphic sleep duration was associated with lower stressfulness expectations, whereas both sleep duration and efficiency were positively linked with daily pleasantness expectations. Only pleasantness expectations (Study 2)-but not daily stressfulness and event expectations (Study 1)-predicted end-of-day physical symptoms. CONCLUSION: Findings suggest the importance of sleep on expectations of next-day stress and positive experiences, of which may have implications for daily physical health.

Enhancer selectivity in space and time: from enhancer-promoter interactions to promoter activation.

The primary regulators of metazoan gene expression are enhancers, originally functionally defined as DNA sequences that can activate transcription at promoters in an orientation-independent and distance-independent manner. Despite being crucial for gene regulation in animals, what mechanisms underlie enhancer selectivity for promoters, and more fundamentally, how enhancers interact with promoters and activate transcription, remain poorly understood. In this Review, we first discuss current models of enhancer-promoter interactions in space and time and how enhancers affect transcription activation. Next, we discuss different mechanisms that mediate enhancer selectivity, including repression, biochemical compatibility and regulation of 3D genome structure. Through 3D polymer simulations, we illustrate how the ability of 3D genome folding mechanisms to mediate enhancer selectivity strongly varies for different enhancer-promoter interaction mechanisms. Finally, we discuss how recent technical advances may provide new insights into mechanisms of enhancer-promoter interactions and how technical biases in methods such as Hi-C and Micro-C and imaging techniques may affect their interpretation.

Specialized digestive mechanism for an insect-bacterium gut symbiosis.

In Burkholderia-Riptortus symbiosis, the host bean bug Riptortus pedestris harbors Burkholderia symbionts in its symbiotic organ, M4 midgut, for use as a nutrient source. After occupying M4, excess Burkholderia symbionts are moved to the M4B region, wherein they are effectively digested and absorbed. Previous studies have shown that M4B has strong symbiont-specific antibacterial activity, which is not because of the expression of antimicrobial peptides but rather because of the expression of digestive enzymes, mainly cathepsin L protease. However, in this study, inhibition of cathepsin L activity did not reduce the bactericidal activity of M4B, indicating that there is an unknown digestive mechanism that renders specifically potent bactericidal activity against Burkholderia symbionts. Transmission electron microscopy revealed that the lumen of symbiotic M4B was filled with a fibrillar matter in contrast to the empty lumen of aposymbiotic M4B. Using chromatographic and electrophoretic analyses, we found that the bactericidal substances in M4B existed as high-molecular-weight (HMW) complexes that were resistant to protease degradation. The bactericidal HMW complexes were visualized on non-denaturing gels using protein- and polysaccharide-staining reagents, thereby indicating that the HMW complexes are composed of proteins and polysaccharides. Strongly stained M4B lumen with Periodic acid-Schiff (PAS) reagent in M4B paraffin sections confirmed HMW complexes with polysaccharide components. Furthermore, M4B smears stained with Periodic acid-Schiff revealed the presence of polysaccharide fibers. Therefore, we propose a key digestive mechanism of M4B: bacteriolytic fibers, polysaccharide fibers associated with digestive enzymes such as cathepsin L, specialized for Burkholderia symbionts in Riptortus gut symbiosis.

Contingency management plus acceptance and commitment therapy for initial cocaine abstinence: Results of a sequential multiple assignment randomized trial (SMART).

BACKGROUND: This study tested an adaptive intervention for optimizing abstinence outcomes over phases of treatment for cocaine use disorder using a SMART design. Phase 1 assessed whether 4 weeks of contingency management (CM) improved response with the addition of Acceptance and Commitment Therapy (ACT). Phase 2 assessed pharmacological augmentation with modafinil (MOD) vs. placebo (PLA) for individuals not achieving abstinence during Phase 1. METHOD: For Phase 1 of treatment, participants (N=118) were randomly allocated to ACT+CM or Drug Counseling (DC+CM), the comparison condition. At week 4, treatment response was defined as the submission of six consecutive cocaine-negative urine drug screens (UDS). Phase 1 non-responders were re-randomized to MOD or PLA as adjunct to their initial treatment. Phase 1 responders continued receiving their initial treatment. Primary outcomes included response rate and proportion of cocaine-negative UDS for Phase 1 and 2. Analyses used Bayesian inference with 80% pre-specified as the posterior probability (PP) threshold constituting moderate evidence that an effect exists. RESULTS: Phase 1 response was higher in the ACT+CM group (24.5%) compared to the DC+CM group (17.5%; PP = 84.5%). In Phase 2, the proportion of cocaine-negative UDS among Phase 1 responders did not differ by initial treatment (PP = 61.8%) but remained higher overall compared to Phase 1 non-responders (PPs > 99%). No evidence of an effect favoring augmentation with MOD was observed. DISCUSSION: Adding ACT to CM increased abstinence initiation. Initial responders were more likely to remain abstinent compared to initial non-responders, for whom modafinil was not an effective pharmacotherapy augmentation strategy.

[Incidence and case fatality rates of cardiovascular diseases in urban and rural community-dwelling populations in eastern, central and western regions of China].

Objective: To evaluate the incidence and case fatality rate of cardiovascular disease (CVD) among populations in urban and rural communities in eastern, central and western regions of China. Methods: The present study was based on the data of the Prospective Urban and Rural Epidemiology (PURE)-China cohort, which enrolled participants who had at least one follow-up visit and complete information on age and sex. Information on baseline demographics, cardiovascular risk factors, and prevention and treatment for CVD were collected. CVD and mortality events were documented using the standardized case report form of the PURE Global Study to assess the incidence and case fatality rate of CVD among populations in urban and rural communities in eastern, central and western China. Results: This study included a total of 47 262 community-dwelling participants (age: (51.1±9.6) years; female, n=27 529, 58.2%) from 115 urban and rural communities in 12 provinces across the eastern, central, and western regions of China. Over a follow-up period of 11.9 (9.5, 12.6) years, 2 686 deaths and 5 873 cardiovascular events were documented. The incidence of CVD was 11.90 (95%CI: 11.60-12.21)/1 000 person-years. A significant difference in CVD incidence was observed across regions (Ptrend<0.001), which was highest in the western provinces (13.99 (95%CI: 13.33-14.65)/1 000 person-years), intermediate in the eastern provinces (11.92 (95%CI: 11.52-12.33)/1 000 person-years), and lowest in the central provinces (8.87 (95%CI: 8.25-9.50)/1 000 person-years). The 1-year case fatality rate of CVD demonstrated an increasing trend from eastern to western regions (eastern: 10.20% (95%CI: 6.95-14.73); central: 13.50% (95%CI: 9.90-18.14); western: 18.62% (95%CI: 14.95-22.94); Ptrend<0.001). Moreover, the incidence of major CVD was consistently higher in rural areas compared with urban areas across eastern (P<0.001), central (P=0.01) and western (P<0.001)_regions, respectively. The 1-year case fatality rate in rural areas was also significantly higher compared with that in urban areas in both eastern (P<0.001) and western regions (P=0.02). Conclusions: The incidence and case fatality rate of CVD were high among middle-aged population in China, especially those in western regions with low socioeconomic levels and in rural areas.

TLR4 Ligation by eNAMPT, a Novel DAMP, is Essential to Sulfur Mustard- Induced Inflammatory Lung Injury and Fibrosis.

Objective: Human and preclinical studies of sulfur mustard (SM)-induced acute and chronic lung injuries highlight the role of unremitting inflammation. We assessed the utility of targeting the novel DAMP and TLR4 ligand, eNAMPT (extracellular nicotinamide phosphoribosyltransferase), utilizing a humanized mAb (ALT-100) in rat models of SM exposure. Methods: Acute (SM 4.2 mg/kg, 24 hrs), subacute (SM 0.8 mg/kg, day 7), subacute (SM 2.1 mg/kg, day 14), and chronic (SM 1.2 mg/kg, day 29) SM models were utilized. Results: Each SM model exhibited significant increases in eNAMPT expression (lung homogenates) and increased levels of phosphorylated NFkB and NOX4. Lung fibrosis (Trichrome staining) was observed in both sub-acute and chronic SM models in conjunction with elevated smooth muscle actin (SMA), TGFß, and IL-1ß expression. SM-exposed rats receiving ALT-100 (1 or 4 mg/kg, weekly) exhibited increased survival, highly significant reductions in histologic/biochemical evidence of lung inflammation and fibrosis (Trichrome staining, decreased pNFkB, SMA, TGFß, NOX4), decreased airways strictures, and decreased plasma cytokine levels (eNAMPT, IL-6, IL-1ß. TNFα). Conclusion: The highly druggable, eNAMPT/TLR4 signaling pathway is a key contributor to SM-induced ROS production, inflammatory lung injury and fibrosis. The ALT-100 mAb is a potential medical countermeasure to address the unmet need to reduce SM-associated lung pathobiology/mortality.

Oxygen-Saturation Targets and Cognitive and Functional Outcomes in Mechanically Ventilated Adults.

Rationale: Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown.Objectives: To compare the effects of lower (90% [range, 88-92%]), intermediate (94% [range, 92-96%]), and higher (98% [range, 96-100%]) oxygen-saturation targets on long-term outcomes.Methods: Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction.Measurements and Main Results: A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91-96%), 95% (93-97%), and 97% (95-99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio [OR], 1.36 [95% confidence interval (CI), 0.92-2.00]), intermediate and higher (adjusted OR, 0.90 [95% CI, 0.62-1.29]), or higher and lower (adjusted OR, 1.22 [95% CI, 0.83-1.79]) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life.Conclusions: Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes.

[Preparation of chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and its effects on wound healing of full-thickness skin defects in rats].

Objective: To prepare the chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and to explore its effects on wound healing of full-thickness skin defects in rats. Methods: The research was an experimental research. Chitin nanofibers were prepared by acid hydrolysis and alkaline extraction method, and then mixed with hyaluronic acid and collagen to prepare chitin/hyaluronic acid/collagen hydrogels (hereinafter referred to as hydrogels). Besides, the hydrogels loaded with mouse adipose-derived stem cells were prepared. Thirty male 12-week-old guinea pigs were divided into negative control group, positive control group, and hydrogel group according to the random number table, with 10 guinea pigs in each group. Ethanol, 4-aminobenzoic acid ethyl ester, or the aforementioned prepared hydrogels without cells were topically applied on both sides of back of guinea pigs respectively for induced contact and stimulated contact, and skin edema and erythema formation were observed at 24 and 48 h after stimulated contact. Adipose-derived stem cells from mice were divided into normal control group cultured routinely and hydrogel group cultured with the aforementioned prepared hydrogels without cells. After 3 d of culture, protein expressions of platelet-derived growth factor-D (PDGF-D), insulin-like growth factor-Ⅰ (IGF-Ⅰ), and transforming growth factor ß1 (TGF-ß1) were detected by Western blotting (n=3). Eight male 8-week-old Sprague-Dawley rats were taken and a circular full-thickness skin defect wound was created on each side of the back. The wounds were divided into blank control group without any treatment and hydrogel group with the aforementioned prepared hydrogels loaded with adipose-derived stem cells applied. Wound healing was observed at 0 (immediately), 2, 4, 8, and 10 d after injury, and the wound healing rate was calculated at 2, 4, 8, and 10 d after injury. Wound tissue samples at 10 d after injury were collected, the new tissue formation was observed by hematoxylin-eosin staining; the concentrations of interleukin-1α (IL-1α), IL-6, IL-4, and IL-10 were detected by enzyme-linked immunosorbent assay method; the expressions of CD16 and CD206 positive cells were observed by immunohistochemical staining and the percentages of positive cells were calculated. The sample numbers in animal experiment were all 8. Results: At 24 h after stimulated contact, no skin edema was observed in the three groups of guinea pigs, and only mild skin erythema was observed in 7 guinea pigs in positive control group. At 48 h after stimulated contact, skin erythema was observed in 8 guinea pigs and skin edema was observed in 4 guinea pigs in positive control group, while no obvious skin erythema or edema was observed in guinea pigs in the other two groups. After 3 d of culture, the protein expression levels of PDGF-D, IGF-I, and TGF-ß1 in adipose-derived stem cells in hydrogel group were significantly higher than those in normal control group (with t values of 12.91, 11.83, and 7.92, respectively, P<0.05). From 0 to 10 d after injury, the wound areas in both groups gradually decreased, and the wounds in hydrogel group were almost completely healed at 10 d after injury. At 4, 8, and 10 d after injury, the wound healing rates in hydrogel group were (38±4)%, (54±5)%, and (69±6)%, respectively, which were significantly higher than (21±6)%, (29±7)%, and (31±7)% in blank control group (with t values of 3.82, 3.97, and 4.05, respectively, Pvalues all <0.05). At 10 d after injury, compared with those in blank control group, the epidermis in wound in hydrogel group was more intact, and there were increases in hair follicles, blood vessels, and other skin appendages. At 10 d after injury, the concentrations of IL-1α and IL-6 in wound tissue in hydrogel group were significantly lower than those in blank control group (with tvalues of 8.21 and 7.99, respectively, P<0.05), while the concentrations of IL-4 and IL-10 were significantly higher than those in blank control group (with tvalues of 6.57 and 9.03, respectively, P<0.05). The percentage of CD16 positive cells in wound tissue in hydrogel group was significantly lower than that in blank control group (t=8.02, P<0.05), while the percentage of CD206 positive cells was significantly higher than that in blank control group (t=7.21, P<0.05). Conclusions: The hydrogel loaded with mouse adipose-derived stem cells is non-allergenic, can promote the secretion of growth factors in adipose-derived stem cells, promote the polarization of macrophages to M2 phenotype in wound tissue in rats with full-thickness skin defects, and alleviate inflammatory reaction, thereby promoting wound healing.

[Clinicopathological analysis of gonadal differentiation of sex development disorder].

Objective: To investigate pathological features and differential diagnosis in the gonads with disorder of sex development. Methods: Thirty-six cases of clinically diagnosed hermaphroditism with gonadal biopsy in the Department of Pathology, the Seventh Medical Center of People's Liberation Army General Hospital from April 2007 to July 2021, were collected. All biopsy pathological sections were reviewed, and the gonadal cases with abnormal pathological morphology were screened out. The clinical and imaging data and karyotype of these cases were reviewed. Additional immunohistochemical staining was performed and relevant literature was reviewed. Results: Seven cases of ovotesticular disorder of sex development (OTDSD) were identified, which were characterized by the presence of testicular and ovarian differentiation in the same individual. All patients were under 15 years old and presented with abnormal appearance of external genitalia, and the ratio of male to female was 2∶5. Ultrasonography showed testicular structure in all female patients and cryptorchidism in all male patients. The most common karyotype was 46, XX. One case with undifferentiated gonadal tissue (UGT) and one case with streak gonads were screened out. UGT germ cells were neither in seminiferous tubules nor in follicles, but randomly distributed in an ovarial-type interstitial background, sometimes accompanied by immature sex cords. Streak gonads resembled UGT without germ cells. FOXL2 was positive in granulosa cells, but negative in Sertoli cells. SOX9 expression was opposite. OCT4 was weakly positively/negatively expressed in oocytes and positively expressed in the germ nuclei of UGT. Conclusions: Four differentiation patterns need to be identified in the gonadal biopsy: ovarian differentiation, testicular differentiation, undifferentiated gonadal tissue and streak gonad. The positive expression of SOX9 indicates testicular differentiation, while the positive expression of FOXL2 confirms ovarian differentiation, and the expression of both markers in the same tissue indicates ovotestis differentiation. It is very important to identify UGT, because that has a high probability of developing into gonadoblastoma in the future.

Frequency of cardiotoxicity following intramuscular administration of epinephrine in emergency department patients with anaphylaxis.

Objectives: Epinephrine can be a life-saving treatment for patients with anaphylaxis. Potential cardiovascular side effects of epinephrine may contribute to clinician hesitancy to use it. However, the frequency of cardiotoxicity resulting from epinephrine treatment for anaphylaxis is not well described. We sought to describe the frequency of cardiotoxicity following intramuscular (IM) administration of epinephrine in adult emergency department (ED) patients with anaphylaxis. Methods: We conducted a retrospective observational study at a single, quaternary care academic ED in Tennessee. We identified consecutive ED visits with the diagnosis of anaphylaxis from 2017 to 2021 who received at least one intramuscular (IM) dose of epinephrine in the ED. Analysis was primarily descriptive. The primary outcome was cardiotoxicity, the occurrence of any of the following after epinephrine administration: ischemic electrocardiogram changes, systolic blood pressure >200 mmHg, or cardiac arrest ≤4 h; elevated troponin ≤12 h; or percutaneous coronary intervention or depressed ejection fraction ≤72 h. Results: Among 338 included patients, 16 (4.7%; 95%CI: 2.8-7.6%) experienced cardiotoxicity. Cardiotoxic events included eight (2.4%) ischemic electrocardiogram changes, six (1.8%) episodes of elevated troponin, five (1.5%) atrial arrhythmias, one (0.3%) ventricular arrythmia, and one (0.3%) depressed ejection fraction. Patients with cardiotoxicity were significantly older, had more comorbidities, and were more likely to have received multiple doses of epinephrine or an epinephrine infusion compared with a single IM dose of epinephrine. Conclusions: Among 338 consecutive adult ED patients who received IM epinephrine for anaphylaxis during a recent 4-year period, cardiotoxic side effects were observed in approximately 5% of patients.

[Observation of the consistency between intellectualized and manual-based cognitive assessment tools in the outpatient clinic].

Objective: The intellectualized versions of the Montreal Cognitive Assessment Scale (MoCA) and the Mini-mental State Examination (MMSE) (i-MoCA/i-MMSE) were developed. The validity of this system was evaluated in a clinical sample through comparing with the manual-based assessments. Methods: A total of 88 patients [aged (66.82±11.37) years, 30 males and 58 females] were enrolled in the outpatient clinic of Xuanwu Hospital of Capital Medical University with complaints of cognitive decline, from February to October 2023. All participants completed manual-based and intellectualized assessments in a randomized order, with an interval of 2 weeks to control for the practice effect. The reliability of the intellectualized version of assessments was evaluated based on the manual-based version using the Concordance correlation coefficient (CCC). The difference between the intellectualized and the manual-based assessments was tested by the Repeated ANCOVA with demographic information controlled. The accuracy of evaluation of the i-MoCA and i-MMSE was analyzed by the Receiver Operating Characteristic (ROC) analysis. Results: High concordance was observed between the intellectualized version and the manual-based assessments (CCCMoCA=0.87, CCCMMSE=0.83). Controlling for basic demographic information, there was no significant difference in the scores of the intellectualized version and the manual-based assessments (all P>0.05). The accuracy of i-MoCA in screening patients with cognitive impairment was 94.3% (sensitivity=94.6%, specificity=78.1%), while the accuracy of i-MMSE in screening patients with cognitive impairment was 94.9% (sensitivity=94.9%, specificity=77.6%). In addition, the majority of subdomains measured by the cognitive assessments exhibited high consistency across the intellectualized the manual-based versions (CCCMoCA=0.32-0.78; CCCMMSE=0.54-0.79). Conclusion: Both the i-MoCA and i-MMSE showed high consistency and diagnostic accuracy with the manual-based versions in terms of overall cognitive function and subdomains.