Prehospital Shock Index Multiplied by the Alert/Verbal/Painful/Unresponsive Score as a Predictor of Clinical Outcomes in Traumatic Injury.

OBJECTIVE: Various prediction scores have been developed to predict mortality in trauma patients, such as the shock index (SI), modified SI (mSI), age-adjusted SI (aSI), and the shock index (SI) multiplied by the alert/verbal/painful/unresponsive (AVPU) score (SIAVPU). The SIAVPU is a novel scoring system but its prediction accuracy for trauma outcomes remains in need of further validation. Therefore, we investigated the accuracy of four scoring systems, including SI, mSI, aSI, and SIAVPU, in predicting mortality, admission to the intensive care unit (ICU), and prolonged hospital length of stay ≥ 30 days (LOS). METHODS: This retrospective multicenter study used data from the Tzu Chi Hospital trauma database. The area under the receiver operating characteristic curve (AUROC) was determined for each outcome to assess their discrimination capabilities and comparing by Delong's test. Subgroup analyses were conducted to investigate the prediction accuracy of the SIAVPU in different patient populations. RESULTS: In total, 5355 patients were included in the analysis. The median of SIAVPU were significantly higher among patients at those with major injury (1.47 vs 0.63), those admitted to the ICU (0.73 vs 0.62), those with prolonged hospital LOS≥ 30 days (0.83 vs 0.64), and those with mortality (1.08 vs 0.64). The AUROC of the SIAVPU was significantly higher than that of the SI, mSI, and aSI for 24-h mortality (AUROC: 0.845 vs 0.533, 0.540, and 0.678), 3-day mortality (AUROC: 0.803 vs 0.513, 0.524, and 0.688), 7-day mortality (AUROC: 0.755 vs 0.494, 0.505, and 0.648), in-hospital mortality (AUROC: 0.722 vs 0.510, 0.524, and 0.667), ICU admission (AUROC: 0.635 vs 0.547, 0.551, and 0.563). At the optimal cutoff value of 0.9, the SIAVPU had an accuracy of 82.2% for predicting 24-h mortality, 82.8% for predicting 3-day mortality, of 82.8% for predicting 7-day mortality, of 82.5% for predicting in-hospital mortality, of 73.9% for predicting Intensive Care Unit (ICU) admission, and of 81.7% for predicting prolonged hospital LOS ≥30 days. CONCLUSIONS: Our results reveal that SIAVPU has better accuracy than the SI, mSI, and aSI for predicting 24-h, 3-day, 7-day, and in-hospital mortality; ICU admission; and prolonged hospital LOS ≥30 days among patients with traumatic injury.

Role of Hedgehog Signaling Pathways in Multipotent Mesenchymal Stem Cells Differentiation.

Multipotent mesenchymal stem cells (MSCs) have high self-renewal and multi-lineage differentiation potentials and low immunogenicity, so they have attracted much attention in the field of regenerative medicine and have a promising clinical application. MSCs originate from the mesoderm and can differentiate not only into osteoblasts, cartilage, adipocytes, and muscle cells but also into ectodermal and endodermal cell lineages across embryonic layers. To design cell therapy for replacement of damaged tissues, it is essential to understand the signaling pathways, which have a major impact on MSC differentiation, as this will help to integrate the signaling inputs to initiate a specific lineage. Hedgehog (Hh) signaling plays a vital role in the development of various tissues and organs in the embryo. As a morphogen, Hh not only regulates the survival and proliferation of tissue progenitor and stem populations but also is a critical moderator of MSC differentiation, involving tri-lineage and across embryonic layer differentiation of MSCs. This review summarizes the role of Hh signaling pathway in the differentiation of MSCs to mesodermal, endodermal, and ectodermal cells.

Efficacy of a sepsis clinical decision support system in identifying patients with sepsis in the emergency department.

BACKGROUND: Early prediction of sepsis onset is crucial for reducing mortality and the overall cost burden of sepsis treatment. Currently, few effective and accurate prediction tools are available for sepsis. Hence, in this study, we developed an effective sepsis clinical decision support system (S-CDSS) to assist emergency physicians to predict sepsis. METHODS: This study included patients who had visited the emergency department (ED) of Taipei Tzu Chi Hospital, Taiwan, between January 1, 2020, and June 31, 2022. The patients were divided into a derivation cohort (n = 70,758) and a validation cohort (n = 27,545). The derivation cohort was subjected to sixfold stratified cross-validation, reserving 20% of the data (n = 11,793) for model testing. The primary study outcome was a sepsis prediction (International Classification of Diseases, Tenth Revision, Clinical Modification) before discharge from the ED. The S-CDSS incorporated the LightGBM algorithm to ensure timely and accurate prediction of sepsis. The validation cohort was subjected to multivariate logistic regression to identify the associations of S-CDSS-based high- and medium-risk alerts with clinical outcomes in the overall patient cohort. For each clinical outcome in high- and medium-risk patients, we calculated the sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and accuracy of S-CDSS-based predictions. RESULTS: The S-CDSS was integrated into our hospital information system. The system featured three risk warning labels (red, yellow, and white, indicating high, medium, and low risks, respectively) to alert emergency physicians. The sensitivity and specificity of the S-CDSS in the derivation cohort were 86.9% and 92.5%, respectively. In the validation cohort, high- and medium-risk alerts were significantly associated with all clinical outcomes, exhibiting high prediction specificity for intubation, general ward admission, intensive care unit admission, ED mortality, and in-hospital mortality (93.29%, 97.32%, 94.03%, 93.04%, and 93.97%, respectively). CONCLUSION: Our findings suggest that the S-CDSS can effectively identify patients with suspected sepsis in the ED. Furthermore, S-CDSS-based predictions appear to be strongly associated with clinical outcomes in patients with sepsis.

Use of Reverse Shock Index Multiplied by Simplified Motor Score in a Five-Level Triage System: Identifying Trauma in Adult Patients at a High Risk of Mortality.

Background and Objectives: The Taiwan Triage and Acuity Scale (TTAS) is reliable for triaging patients in emergency departments in Taiwan; however, most triage decisions are still based on chief complaints. The reverse-shock index (SI) multiplied by the simplified motor score (rSI-sMS) is a more comprehensive approach to triage that combines the SI and a modified consciousness assessment. We investigated the combination of the TTAS and rSI-sMS for triage compared with either parameter alone as well as the SI and modified SI. Materials and Methods: We analyzed 13,144 patients with trauma from the Taipei Tzu Chi Trauma Database. We investigated the prioritization performance of the TTAS, rSI-sMS, and their combination. A subgroup analysis was performed to evaluate the trends in all clinical outcomes for different rSI-sMS values. The sensitivity and specificity of rSI-sMS were investigated at a cutoff value of 4 (based on previous study and the highest score of the Youden Index) in predicting injury severity clinical outcomes under the TTAS system were also investigated. Results: Compared with patients in triage level III, those in triage levels I and II had higher odds ratios for major injury (as indicated by revised trauma score < 7 and injury severity score [ISS] ≥ 16), intensive care unit (ICU) admission, prolonged ICU stay (≥14 days), prolonged hospital stay (≥30 days), and mortality. In all three triage levels, the rSI-sMS < 4 group had severe injury and worse outcomes than the rSI-sMS ≥ 4 group. The TTAS and rSI-sMS had higher area under the receiver operating characteristic curves (AUROCs) for mortality, ICU admission, prolonged ICU stay, and prolonged hospital stay than the SI and modified SI. The combination of the TTAS and rSI-sMS had the highest AUROC for all clinical outcomes. The prediction performance of rSI-sMS < 4 for major injury (ISS ≥ 16) exhibited 81.49% specificity in triage levels I and II and 87.6% specificity in triage level III. The specificity for mortality was 79.2% in triage levels I and II and 87.4% in triage level III. Conclusions: The combination of rSI-sMS and the TTAS yielded superior prioritization performance to TTAS alone. The integration of rSI-sMS and TTAS effectively enhances the efficiency and accuracy of identifying trauma patients at a high risk of mortality.

Analysis of outcomes and prognostic factor in acute type A aortic dissection complicated with preoperative shock: A single-center study.

BACKGROUND: Acute type A aortic dissection (ATAAD) is a critical cardiovascular emergency that requires prompt surgical intervention for preserving life, particularly in patients with critical preoperative status. This retrospective study aimed to investigate the clinical features, early and late outcomes, and prognostic factors in patients undergoing aortic repair surgery for ATAAD complicated with preoperative shock. METHODS: Between April 2007 and July 2020, 694 consecutive patients underwent emergency ATAAD repair at our institution, including 162 (23.3%) presenting with preoperative shock (systolic blood pressure <90 mm Hg), who were classified into the survivor (n = 125) and non-survivor (n = 37) groups according to whether they survived to hospital discharge. The clinical demographics, surgical information, and postoperative complications were compared. Five-year survival and freedom from reoperation rates of survivors were analyzed using the Kaplan-Meier actuarial method. Multivariate logistic regression analysis was used to identify independent risk factors for in-hospital mortality. RESULTS: The in-hospital surgical mortality rate in patients with ATAAD and shock was 22.8%. The non-survivor group showed higher rates of preoperative cardiopulmonary resuscitation, acute myocardial infarction, and cerebral infarction, and was associated with longer cardiopulmonary bypass time, higher rates of total arch replacement and intraoperative extracorporeal membrane oxygenation implementation. The non-survivor group had higher blood transfusion volumes and rates of malperfusion-related complications. Multivariate analysis revealed that preoperative cardiopulmonary resuscitation, prolonged cardiopulmonary bypass time, and total arch replacement were risk factors for in-hospital mortality. For patients who survived to discharge, the 5-year cumulative survival and freedom from aortic reoperation rates were 75.6% (95% confidence interval, 67.6%-83.6%) and 82.6% (95% confidence interval, 74.2%-91.1%), respectively. CONCLUSIONS: Preoperative shock in ATAAD is associated with a high risk of in-hospital mortality, particularly in patients who undergo cardiopulmonary resuscitation and complex aortic repair procedures with extended cardiopulmonary bypass. However, late outcomes are acceptable for patients who were stabilized through surgical treatment and survived to discharge.

Acute type a aortic intramural hematoma complicated with preoperative hemopericardium: early and late surgical outcome analyses.

BACKGROUND: Acute type A aortic intramural hematoma (ATAIMH) is a variant of acute type A aortic dissection (ATAAD), exhibiting an increased risk of hemopericardium and cardiac tamponade. It can be life-threatening without emergency treatment. However, comprehensive studies of the clinical features and surgical outcomes of preoperative hemopericardium in patients with ATAIMH remain scarce. This retrospective study aims to investigate the clinical features and early and late outcomes of patients who underwent aortic repair surgery for ATAIMH complicated with preoperative hemopericardium. METHODS: We investigated 132 consecutive patients who underwent emergency ATAIMH repair at this institution between February 2007 and August 2020. These patients were dichotomized into the hemopericardium (n = 58; 43.9%) and non-hemopericardium groups (n = 74; 56.1%). We compared the clinical demographics, surgical information, postoperative complications, 5-year cumulative survival rates, and freedom from reoperation rates. Furthermore, multivariable logistic regression analysis was utilized to identify independent risk factors for patients who underwent re-exploration for bleeding. RESULTS: In the hemopericardium group, 36.2% of patients presented with cardiac tamponade before surgery. Moreover, the hemopericardium group showed higher rates of preoperative shock and endotracheal intubation and was associated with an elevated incidence of intractable perioperative bleeding, necessitating delayed sternal closure for hemostasis. The hemopericardium group exhibited higher blood transfusion volumes and rates of re-exploration for bleeding following surgery. However, the 5-year survival (59.5% vs. 75.0%; P = 0.077) and freedom from reoperation rates (93.3% vs. 85.5%; P = 0.416) were comparable between both groups. Multivariable analysis revealed that hemopericardium, cardiopulmonary bypass time, and delayed sternal closure were the risk factors for bleeding re-exploration. CONCLUSIONS: The presence of hemopericardium in patients with ATAIMH is associated with an elevated incidence of cardiac tamponade and unstable preoperative hemodynamics, which could lead to perioperative bleeding tendencies and high complication rates. However, patients of ATAIMH complicated with hemopericardium undergoing aggressive surgical intervention exhibited long-term surgical outcomes comparable to those without hemopericardium.

Reverse shock index multiplied by simplified motor score as a predictor of clinical outcomes for patients with COVID-19.

BACKGROUND: The reverse shock index (rSI) combined with the Simplified Motor Score (sMS), that is, the rSI-sMS, is a novel and efficient prehospital triage scoring system for patients with COVID-19. In this study, we evaluated the predictive accuracy of the rSI-sMS for general ward and intensive care unit (ICU) admission among patients with COVID-19 and compared it with that of other measures, including the shock index (SI), modified SI (mSI), rSI combined with the Glasgow Coma Scale (rSI-GCS), and rSI combined with the GCS motor subscale (rSI-GCSM). METHODS: All patients who visited the emergency department of Taipei Tzu Chi Hospital between January 2021 and June 2022 were included in this retrospective cohort. A diagnosis of COVID-19 was confirmed through a SARS-CoV-2 reverse-transcription polymerase chain reaction test or SARS-CoV-2 rapid test with oropharyngeal or nasopharyngeal swabs and was double confirmed by checking International Classification of Diseases, Tenth Revision, Clinical Modification codes in electronic medical records. In-hospital mortality was regarded as the primary outcome, and sepsis, general ward or ICU admission, endotracheal intubation, and total hospital length of stay (LOS) were regarded as secondary outcomes. Multivariate logistic regression was used to determine the relationship between the scoring systems and the three major outcomes of patients with COVID-19, including. The discriminant ability of the predictive scoring systems was investigated using the area under the receiver operating characteristic curve, and the most favorable cutoff value of the rSI-sMS for each major outcome was determined using Youden's index. RESULTS: After 74,183 patients younger than 20 years (n = 11,572) and without COVID-19 (n = 62,611) were excluded, 9,282 patients with COVID-19 (median age: 45 years, interquartile range: 33-60 years, 46.1% men) were identified as eligible for inclusion in the study. The rate of in-hospital mortality was determined to be 0.75%. The rSI-sMS scores were significantly lower in the patient groups with sepsis, hyperlactatemia, admission to a general ward, admission to the ICU, total length of stay ≥ 14 days, and mortality. Compared with the SI, mSI, and rSI-GCSM, the rSI-sMS exhibited a significantly higher accuracy for predicting general ward admission, ICU admission, and mortality but a similar accuracy to that of the rSI-GCS. The optimal cutoff values of the rSI-sMS for predicting general ward admission, ICU admission, and mortality were calculated to be 3.17, 3.45, and 3.15, respectively, with a predictive accuracy of 86.83%, 81.94%%, and 90.96%, respectively. CONCLUSIONS: Compared with the SI, mSI, and rSI-GCSM, the rSI-sMS has a higher predictive accuracy for general ward admission, ICU admission, and mortality among patients with COVID-19.

The conformational landscape of human transthyretin revealed by cryo-EM.

Transthyretin (TTR) is a natively tetrameric thyroxine transporter found in blood and cerebrospinal fluid whose misfolding and aggregation causes transthyretin amyloidosis. A rational drug design campaign identified the small molecule tafamidis (Vyndaqel/Vyndamax) as an effective stabilizer of the native TTR fold, and this aggregation inhibitor is regulatory agency-approved for the treatment of TTR amyloidosis. Despite 50 years of structural studies on TTR and this triumph of structure-based drug design, there remains a notable dearth of structural information available to understand ligand binding allostery and amyloidogenic TTR unfolding intermediates. We used single-particle cryo-electron microscopy (cryo-EM) to investigate the conformational landscape of this 55 kiloDalton tetramer in the absence and presence of one or two ligands, revealing inherent asymmetries in the tetrameric architecture and previously unobserved conformational states. These findings provide critical mechanistic insights into negatively cooperative ligand binding and the structural pathways responsible for TTR amyloidogenesis. This study underscores the capacity of cryo-EM to provide new insights into protein structures that have been historically considered too small to visualize and to identify pharmacological targets suppressed by the confines of the crystal lattice, opening uncharted territory in structure-based drug design.

Assessing the Impact of the COVID-19 Pandemic on Pediatric Emergency Department Visits in Taiwan.

Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic has profoundly impacted healthcare systems worldwide. To assess the effects of the pandemic on pediatric emergency department (ED) visits in Taiwan, we conducted a study to evaluate changes in pediatric ED visits during the COVID-19 pandemic. Materials and Methods: This retrospective study included pediatric patients (age ≤ 18) who visited the ED between 21 January 2019 and 30 April 2019, at three hospitals of the Cathay Health System, and compared them with a corresponding period in 2020. Basic information, including mode of arrival, triage level, disposition, chief complaints, and incidence rates, were analyzed before and during the pandemic. Results: A total of 10,116 patients, with 6009 in the pre-pandemic group and 4107 in the pandemic group, were included in this study. The mean number of daily pediatric ED visits decreased from 60.09 before the pandemic to 40.66 during the pandemic, while ambulance use increased significantly by 2.56%. The percentage of patients with high acuity triage levels (levels 1 and 2) was significantly lower during the pandemic period (0.63% and 10.18%, respectively) than the pre-pandemic period (0.7% and 10.9%, respectively). Additionally, a significantly higher proportion of patients were discharged during the pandemic period (89.36%) than during the pre-pandemic period (88.33%). The proportion of COVID-19-related complaints, such as fever and respiratory tract infections, as well as other complaints including gastrointestinal issues, trauma, and psychological problems, significantly increased during the pandemic. Conclusions: In preparation for future pandemics, we recommend increasing emergency medical service capacity, establishing a non-contagious route for obtaining chronic medication prescriptions, optimizing staff allocation in pediatric emergency departments, and increasing the number of hospital social workers for enhanced support.

High-resolution single-particle imaging at 100-200 keV with the Gatan Alpine direct electron detector.

Developments in direct electron detector technology have played a pivotal role in enabling high-resolution structural studies by cryo-EM at 200 and 300 keV. Yet, theory and recent experiments indicate advantages to imaging at 100 keV, energies for which the current detectors have not been optimized. In this study, we evaluated the Gatan Alpine detector, designed for operation at 100 and 200 keV. Compared to the Gatan K3, Alpine demonstrated a significant DQE improvement at these voltages, specifically a ~4-fold improvement at Nyquist at 100 keV. In single-particle cryo-EM experiments, Alpine datasets yielded better than 2 Å resolution reconstructions of apoferritin at 120 and 200 keV on a ThermoFisher Scientific (TFS) Glacios microscope. We also achieved a ~3.2 Å resolution reconstruction for a 115 kDa asymmetric protein complex, proving its effectiveness with complex biological samples. In-depth analysis revealed that Alpine reconstructions are comparable to K3 reconstructions at 200 keV, and remarkably, reconstruction from Alpine at 120 keV on a TFS Glacios surpassed all but the 300 keV data from a TFS Titan Krios with GIF/K3. Additionally, we show Alpine's capability for high-resolution data acquisition and screening on lower-end systems by obtaining ~3 Å resolution reconstructions of apoferritin and aldolase at 100 keV and detailed 2D averages of a 55 kDa sample using a side-entry cryo holder. Overall, we show that Gatan Alpine performs well with the standard 200 keV imaging systems and may potentially capture the benefits of lower accelerating voltages, possibly bringing smaller sized particles within the scope of cryo-EM.

Parenting self-efficacy and parenting stress mediates the effects of the association of perceived social support and readiness for discharge among parents of children with primary nephrotic syndrome.

PURPOSE: To investigate the level of readiness for discharge among parents of children with primary nephrotic syndrome and to explore the mediating role of parenting self-efficacy and parenting stress between perceived social support and readiness for discharge. DESIGN AND METHODS: A cross-sectional study was conducted in five large tertiary general hospitals in Hunan, China. Data related to demographics, perceived social support, parenting self-efficacy, parenting stress, and readiness for discharge were collected from 350 parents of children diagnosed with primary nephrotic syndrome. Path analysis was used to determine the mediating roles of parenting self-efficacy and parenting stress in the relationship between perceived social support and readiness for discharge. RESULTS: Parents of children with nephrotic syndrome in China experienced low perceived social support, low readiness for discharge, and high parenting stress. Factors influencing readiness for discharge include the child's age, duration of illness, first episode or relapse, parental literacy and marital status. Parenting self-efficacy and parenting stress mediated the effects of the association of perceived social support and readiness for discharge. CONCLUSION: Perceived social support influences the readiness of parents of children with nephrotic syndrome. Parenting self-efficacy and parenting stress have a chain mediating effect of the association of perceived social support and readiness for discharge. PRACTICE IMPLICATIONS: This study emphasizes the mediating role of the psychological state of the child's parents. Nurses should take steps to increase perceived social support and parenting self-efficacy of the child's parents and to reduce parenting stress in order to improve readiness for discharge.

A Ten-Year Retrospective Cohort Study on Neck Collar Immobilization in Trauma Patients with Head and Neck Injuries.

Background and Objectives: In the context of prehospital care, spinal immobilization is commonly employed to maintain cervical stability in head and neck injury patients. However, its use in cases of unclear consciousness or major trauma patients is often precautionary, pending the exclusion of unstable spinal injuries through appropriate diagnostic imaging. The impact of prehospital C-spinal immobilization in these specific patient populations remains uncertain. Materials and Methods: We conducted a retrospective cohort study at Taipei Tzu Chi Hospital from January 2009 to May 2019, focusing on trauma patients suspected of head and neck injuries. The primary outcome assessed was in-hospital mortality. We employed multivariable logistic regression to investigate the relationship between prehospital C-spine immobilization and outcomes, while adjusting for various factors such as age, gender, type of traumatic brain injury, Injury Severity Score (ISS), Revised Trauma Score (RTS), and activation of trauma team. Results: Our analysis encompassed 2733 patients. Among these, patients in the unclear consciousness group (GCS ≤ 8) who underwent C-spine immobilization exhibited a higher mortality rate than those without immobilization. However, there was no statistically significant difference in mortality among patients with alert consciousness (GCS > 8). Multivariable logistic regression analysis revealed that advanced age (age ≥ 65), unclear consciousness (GCS ≤ 8), major traumatic injuries (ISS ≥ 16 and RTS ≤ 7), and the use of neck collars for immobilization (adjusted OR: 1.850, 95% CI: 1.240-2.760, p = 0.003) were significantly associated with an increased risk of mortality. Subgroup analysis indicated that C-spine immobilization was significantly linked to an elevated risk of mortality in older adults (age ≥ 65), patients with unclear consciousness (GCS ≤ 8), those with major traumatic injuries (ISS ≥ 16 and RTS ≤ 7), and individuals in shock (shock index > 1). Conclusions: While our findings do not advocate for the complete abandonment of neck collars in all suspected head and neck injury patients, our study suggests that prehospital cervical and spinal immobilization should be applied more selectively in certain head and neck injury populations. This approach is particularly relevant for older individuals (age ≥ 65), those with unclear consciousness (GCS ≤ 8), individuals experiencing major traumatic injuries (ISS ≥ 16 or RTS ≤ 7), and patients in a state of shock (shock index ≥ 1). Our study employs a retrospective cohort design, which may introduce selection bias. Therefore, in the future, there is a need for confirmation of our results through a two-arm randomized controlled trial (RCT) arises, as this design is considered ideal for addressing this issue.

Local structural flexibility drives oligomorphism in computationally designed protein assemblies.

Many naturally occurring protein assemblies have dynamic structures that allow them to perform specialized functions. For example, clathrin coats adopt a wide variety of architectures to adapt to vesicular cargos of various sizes. Although computational methods for designing novel self-assembling proteins have advanced substantially over the past decade, most existing methods focus on designing static structures with high accuracy. Here we characterize the structures of three distinct computationally designed protein assemblies that each form multiple unanticipated architectures, and identify flexibility in specific regions of the subunits of each assembly as the source of structural diversity. Cryo-EM single-particle reconstructions and native mass spectrometry showed that only two distinct architectures were observed in two of the three cases, while we obtained six cryo-EM reconstructions that likely represent a subset of the architectures present in solution in the third case. Structural modeling and molecular dynamics simulations indicated that the surprising observation of a defined range of architectures, instead of non-specific aggregation, can be explained by constrained flexibility within the building blocks. Our results suggest that deliberate use of structural flexibility as a design principle will allow exploration of previously inaccessible structural and functional space in designed protein assemblies.

Comparison of clinical outcomes in critical patients undergoing different mechanical ventilation modes: a systematic review and network meta-analysis.

Purpose: To evaluate the effects of different mechanical ventilation modes on critical patients. Methods: PubMed, Embase, Web of science, and Cochrane Library databases were searched from their inception to November 15, 2022 for randomized controlled trials on the application of different mechanical ventilation modes in critical patients. Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. R4.2.1 was used for this network meta-analysis. Results: Twenty-eight RCTs involving 3,189 patients were included. The interventions in these RCTs included NAVA (neurally adjusted ventilatory assist), PAV (proportional assist ventilation), ASV (adaptive support ventilation), Smartcare/PS (Smartcare/pressure support), PSV (pressure support ventilation), PSV_ATC (pressure support ventilation_automatic tube compensation), and SIMV (synchronized intermittent mandatory ventilation). The network meta-analysis showed that, compared with the PSV group, there was no significant difference in duration of mechanical ventilation, duration of ICU stay, and hospital stay between NAVA, SIMV, AVS, PAV, Smartcare/PS, and PSV_ATC groups. Compared with PSV, PAV improved the success rate of withdrawal of ventilator [OR = 3.07, 95%CI (1.21, 8.52)]. Compared with PSV and PAV, NAVA reduced mortality in the ICU [OR = 0.63, 95%CI (0.43, 0.93); OR = 0.45, 95%CI (0.21, 0.97)]. Conclusion: NAVA can reduce mortality in ICU, and PAV may increase the risk of withdrawal of the ventilator. There was no significant difference between PSV and other mechanical ventilation modes (NAVA, SIMV, AVS, PAV, Smartcare/PS, and PSV_ATC) in the duration of mechanical ventilation, duration of ICU stay, or hospital stay. Due to the limitations, more high-quality studies are needed to verify these findings.

Macroscopic on­site quality evaluation of biopsy specimens to improve the diagnostic accuracy of endoscopic ultrasound­guided fine needle aspiration using a 22­gauge needle for solid lesions: A single­center retrospective study.

The present study aimed to evaluate the clinical value of macroscopic on-site evaluation (MOSE) of solid masses by endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) using a standard 22-gauge needle and to explore the cut-off length of macroscopic visible core (MVC) required to obtain an accurate histopathological diagnosis. In total, 119 patients who satisfied the inclusion and exclusion criteria and underwent EUS-FNA were divided into conventional FNA and FNA combined with MOSE groups. In the MOSE group, the presence of MVC was examined and its total length measured, after which the pathological results of FNA were compared with the final diagnosis. The diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of FNA in the two groups were calculated and the effect of MOSE on the FNA result was analyzed. The MOSE group had a higher diagnostic sensitivity (75.0% vs. 89.8%; P=0.038) and accuracy (74.5% vs. 90.6%; P=0.026). MVC was observed in 98.4% (63/64) of patients in the MOSE group. The median length of MVC was 15 mm. The optimal cut-off length of MVC for obtaining an accurate histological diagnosis was 13 mm, with a sensitivity of 90.2%. No statistically significant significance was observed in the specificity, PPV and NPV between the groups. Thus, MOSE helps to improve the diagnostic ability of FNA for solid masses and may be a useful alternative to assess the adequacy of puncture specimens in units where rapid on-site evaluation cannot be performed.

Preliminary study on the role of aryl hydrocarbon receptor in the neurotoxicity of three typical bisphenol compounds (BPA, BPS and TBBPA) at environmentally relevant concentrations to adult zebrafish (Danio rerio).

Objective: This study was aimed to explore the role of AhR in the neurotoxicity of adult zebrafish induced by three typical bisphenol compounds (BPA, BPS, TBBPA) at environmentally relevant doses. Methods: The adult zebrafish were randomly divided into solvent control group (DMSO) and AhR inhibitor CH223191 (CH) group (0.05 µmol/L), bisphenol exposure groups (10, 100, 1000 nmol/L) and combined exposure groups (0.05 µmol/L CH and 1000 nmol/L bisphenol compounds). Each tank contained 8 fish (4 male and 4 female), and two parallel tanks were set synchronously. After 30 days of exposure, zebrafish were put on ice plate for anesthesia, weighed and measured for body length, and dissected for brain tissue. The gene expression was detected by RT-qPCR, and the activities of antioxidant enzymes were detected by commercial kits. SPSS 26.0 was used to analyze the data. Additionally, GO, KEGG and principal component analysis (PCA) were carried out. Results: Compared with the solvent control group, there were no significant differences in body weight and length among the exposed groups. In general, exposure to bisphenol compounds could affect the expression of Ahr2 and AhR target genes (cyp1a1, cyp1a2, and cyp1c1), key genes of neural function (elavl3, gfap, mbp, syn2a, gap43, Zn5, shha, and ache), oxidative stress related genes (nrf2, gpx1a, gstp1/gstp1.2, gstp2/gstp1.1, sod1, sod2, and cat), and the activities of antioxidant enzymes (SOD, CAT and GSH-Px/GPX) in zebrafish brain tissue to some extent. Compared with the groups exposed to bisphenols alone, CH could antagonize the above interference effects caused by bisphenols to some extent. Therefore, the toxic effects of BPA, BPS and TBBPA might be produced through similar mechanisms. Conclusion: Environmentally related doses of bisphenols (BPA, BPS, TBBPA) could disturb the expression of key molecules of oxidative stress and neural function through activating the AhR signaling pathway, and ultimately lead to neurotoxicity.

Discriminant ability of the shock index, modified shock index, and reverse shock index multiplied by the Glasgow coma scale on mortality in adult trauma patients: a PATOS retrospective cohort study.

BACKGROUND: The shock index (SI) predicts short-term mortality in trauma patients. Other shock indices have been developed to improve discriminant accuracy. The authors examined the discriminant ability of the SI, modified SI (MSI), and reverse SI multiplied by the Glasgow Coma Scale (rSIG) on short-term mortality and functional outcomes. METHODS: The authors evaluated a cohort of adult trauma patients transported to emergency departments. The first vital signs were used to calculate the SI, MSI, and rSIG. The areas under the receiver operating characteristic curves and test results were used to compare the discriminant performance of the indices on short-term mortality and poor functional outcomes. A subgroup analysis of geriatric patients with traumatic brain injury, penetrating injury, and nonpenetrating injury was performed. RESULTS: A total of 105 641 patients (49±20 years, 62% male) met the inclusion criteria. The rSIG had the highest areas under the receiver operating characteristic curve for short-term mortality (0.800, CI: 0.791-0.809) and poor functional outcome (0.596, CI: 0.590-0.602). The cutoff for rSIG was 18 for short-term mortality and poor functional outcomes with sensitivities of 0.668 and 0.371 and specificities of 0.805 and 0.813, respectively. The positive predictive values were 9.57% and 22.31%, and the negative predictive values were 98.74% and 89.97%. rSIG also had better discriminant ability in geriatrics, traumatic brain injury, and nonpenetrating injury. CONCLUSION: The rSIG with a cutoff of 18 was accurate for short-term mortality in Asian adult trauma patients. Moreover, rSIG discriminates poor functional outcomes better than the commonly used SI and MSI.