Clot-based time attenuation curve as a novel imaging predictor of mechanical thrombectomy functional outcome in acute ischemia stroke.

OBJECTIVES: To investigate whether a novel assessment of thrombus permeability obtained from perfusion computed tomography (CTP) can act as a more accurate predictor of clinical response to mechanical thrombectomy (MT) in acute ischemic stroke (AIS). MATERIALS AND METHODS: We performed a study including two cohorts of AIS patients who underwent MT admitted to a single-center between April 2018 and February 2022: a retrospective development cohort (n = 71) and a prospective independent validation cohort (n = 96). Thrombus permeability was determined in terms of entire thrombus time-attenuation curve (TAC) on CTP. Association between thrombus TAC distributions and histopathological results was analyzed in the development cohort. Logistic regression was used to assess the performance of the TAC for predicting 90-day modified Rankin Scale (mRS) score, and good outcome was defined as a mRS score of ≤ 2. Basic clinical characteristics was used to build a routine clinical model. A combined model gathered TAC and basic clinical characteristics was also developed. The performance of the three models is compared on the independent validation set. RESULTS: Two TAC distributions were observed-unimodal (uTAC) and linear (lTAC). TAC distributions achieved strong correlations (|r|= 0.627, p < 0.001) with histopathological results, in which uTAC associated with fibrin- and platelet-rich clot while lTAC associated with red blood cell-rich clot. The uTAC was independently associated with poor outcome (odds ratio, 0.08 [95% confidence interval (CI), 0.02-0.31]; p < 0.001). TAC distributions yielded an AUC of 0.78 (95% CI, 0.70-0.87) for predicting clinical outcome. When combined clinical characteristics, the performance was significantly improved (AUC, 0.85 [95% CI, 0.76-0.93]; p < 0.001) and higher than routine clinical model (AUC, 0.69 [95% CI, 0.59-0.83]; p < 0.001). CONCLUSIONS: Thrombus TAC on CTP were found to be a promising new imaging biomarker to predict the outcomes of MT in AIS. CLINICAL RELEVANCE STATEMENT: This study revealed that clot-based time attenuation curve based on admission perfusion CT could reflect the permeability and composition of thrombus and, also, provide valuable information to predict the clinical outcomes of mechanical thrombectomy in patients with acute ischemia stroke. KEY POINTS: • Two time-attenuation curves distributions achieved strong correlations (|r|= 0.627, p < 0.001) with histopathological results. • The unimodal time-attenuation curve was independently associated with poor outcome (odds ratio, 0.08 [0.02-0.31]; p < 0.001). • The time-attenuation curve distributions yielded a higher performance for detecting clinical outcome than routine clinical model (AUC, 0.78 [0.70-0.87] vs 0.69 [0.59-0.83]; p < 0.001).

Deep learning-based automatic ASPECTS calculation can improve diagnosis efficiency in patients with acute ischemic stroke: a multicenter study.

OBJECTIVES: The Alberta Stroke Program Early CT Score (ASPECTS), a systematic method for assessing ischemic changes in acute ischemic stroke using non-contrast computed tomography (NCCT), is often interpreted relying on expert experience and can vary between readers. This study aimed to develop a clinically applicable automatic ASPECTS system employing deep learning (DL). METHODS: This study enrolled 1987 NCCT scans that were retrospectively collected from four centers between January 2017 and October 2021. A DL-based system for automated ASPECTS assessment was trained on a development cohort (N = 1767) and validated on an independent test cohort (N = 220). The consensus of experienced physicians was regarded as a reference standard. The validity and reliability of the proposed system were assessed against physicians' readings. A real-world prospective application study with 13,399 patients was used for system validation in clinical contexts. RESULTS: The DL-based system achieved an area under the receiver operating characteristic curve (AUC) of 84.97% and an intraclass correlation coefficient (ICC) of 0.84 for overall-level analysis on the test cohort. The system's diagnostic sensitivity was 94.61% for patients with dichotomized ASPECTS at a threshold of ≥ 6, with substantial agreement (ICC = 0.65) with expert ratings. Combining the system with physicians improved AUC from 67.43 to 89.76%, reducing diagnosis time from 130.6 ± 66.3 s to 33.3 ± 8.3 s (p < 0.001). During the application in clinical contexts, 94.0% (12,591) of scans successfully processed by the system were utilized by clinicians, and 96% of physicians acknowledged significant improvement in work efficiency. CONCLUSION: The proposed DL-based system could accurately and rapidly determine ASPECTS, which might facilitate clinical workflow for early intervention. CLINICAL RELEVANCE STATEMENT: The deep learning-based automated ASPECTS evaluation system can accurately and rapidly determine ASPECTS for early intervention in clinical workflows, reducing processing time for physicians by 74.8%, but still requires validation by physicians when in clinical applications. KEY POINTS: The deep learning-based system for ASPECTS quantification has been shown to be non-inferior to expert-rated ASPECTS. This system improved the consistency of ASPECTS evaluation and reduced processing time to 33.3 seconds per scan. 94.0% of scans successfully processed by the system were utilized by clinicians during the prospective clinical application.

Effect of Volatile Anesthesia Versus Intravenous Anesthesia on Postoperative Pulmonary Complications in Patients Undergoing Minimally Invasive Esophagectomy: A Randomized Clinical Trial.

BACKGROUND: The effect of intraoperative anesthetic regimen on pulmonary outcome after minimally invasive esophagectomy for esophageal cancer is yet undetermined. The aim of this study was to determine the effect of volatile anesthesia (sevoflurane or desflurane) compared with propofol-based intravenous anesthesia on pulmonary complications after minimally invasive esophagectomy. METHODS: Patients scheduled for minimally invasive esophagectomy were randomly assigned to 1 of 3 general anesthetic regimens (sevoflurane, desflurane, or propofol). The primary outcome was the incidence of pulmonary complications within the 7 days postoperatively, which was a collapsed composite end point, including respiratory infection, pleural effusion, pneumothorax, atelectasis, respiratory failure, bronchospasm, pulmonary embolism, and aspiration pneumonitis. The severity of pulmonary complications, surgery-related complications, and other secondary outcomes were also assessed. RESULTS: Of 647 patients assessed for eligibility, 558 were randomized, and 553 were analyzed. A total of 185 patients were assigned to the sevoflurane group, 185 in the desflurane, and 183 in the propofol group. Patients receiving a volatile anesthetic (sevoflurane or desflurane) had a significantly lower incidence (36.5% vs 47.5%; odds ratio, 0.63; 95% confidence interval, 0.44-0.91; P = .013) and lower severity grade of pulmonary complications ( P = .035) compared to the patients receiving propofol. There were no statistically significant differences in other secondary outcomes between the 2 groups. CONCLUSIONS: In patients undergoing minimally invasive esophagectomy, the use of volatile anesthesia (sevoflurane or desflurane) resulted in the reduced risk and severity of pulmonary complications within the first 7 postoperative days as compared to propofol-based intravenous anesthesia.

Balancing activation and co-stimulation of CAR tunes signaling dynamics and enhances therapeutic potency.

CD19-targeting chimeric antigen receptors (CARs) with CD28 and CD3ζ signaling domains have been approved by the US FDA for treating B cell malignancies. Mutation of immunoreceptor tyrosine-based activation motifs (ITAMs) in CD3ζ generated a single-ITAM containing 1XX CAR, which displayed superior antitumor activity in a leukemia mouse model. Here, we investigated whether the 1XX design could enhance therapeutic potency against solid tumors. We constructed both CD19- and AXL-specific 1XX CARs and compared their in vitro and in vivo functions with their wild-type (WT) counterparts. 1XX CARs showed better antitumor efficacy in both pancreatic and melanoma mouse models. Detailed analysis revealed that 1XX CAR-T cells persisted longer in vivo and had a higher percentage of central memory cells. With fluorescence resonance energy transfer (FRET)-based biosensors, we found that decreased ITAM numbers in 1XX resulted in similar 70-kDa zeta chain-associated protein (ZAP70) activation, while 1XX induced higher Ca2+ elevation and faster extracellular signal-regulated kinase (Erk) activation than WT CAR. Thus, our results confirmed the superiority of 1XX against two targets in different solid tumor models and shed light on the underlying molecular mechanism of CAR signaling, paving the way for the clinical applications of 1XX CARs against solid tumors.

Exploiting Ca2+ signaling in T cells to advance cancer immunotherapy.

Decades of basic research has established the importance of Ca2+ to various T cell functions, such as cytotoxicity, proliferation, differentiation and cytokine secretion. We now have a good understanding of how proximal TCR signaling initiates Ca2+ influx and how this influx subsequently changes transcriptional activities in T cells. As chimeric antigen receptor (CAR)-T therapy has achieved great clinical success, is it possible to harness Ca2+ signaling to further advance CAR-T research? How is CAR signaling different from TCR signaling? How can functional CARs be identified in a high-throughput way? Quantification of various Ca2+ signals downstream of CAR/TCR activation might help answer these questions. Here we first summarized recent studies that used Ca2+ dye, genetically-encoded Ca2+ indicators (GECI) or transcriptional activity reporters to understand CAR activation in vitro and in vivo. We next reviewed several proof-of-concept reports that manipulate Ca2+ signaling by light or ultrasound to achieve precise spatiotemporal control of T cell functions. These efforts, though preliminary, opened up new avenues to solve the on-target/off-tumor problem of therapeutic T cells. Other modalities to regulate Ca2+ signaling, such as radio wave and electrical pulse, were also discussed. Thus, monitoring or manipulating Ca2+ signaling in T cells provides us many opportunities to advance cancer immunotherapy.

Metagenomic profiling of cecal microbiota and antibiotic resistome in rodents.

The rodent gut microbiota is a known reservoir of antimicrobial resistance, yet the distribution of antibiotic resistance genes (ARGs) within rodent cecal microbial communities and the specific bacterial species harboring these ARGs remain largely underexplored. This study employed high-throughput sequencing of 122 samples from five distinct rodent species to comprehensively profile the diversity and distribution of ARGs and to identify the bacterial hosts of these genes. A gene catalog of the rodent cecal microbiome was constructed, comprising 22,757,369 non-redundant genes. Analysis of the microbial composition and diversity revealed that Bacillota and Bacteroidota were the dominant bacterial phyla across different rodent species, with significant variations in species composition among the rodents. In total, 3703 putative antimicrobial resistance protein-coding genes were identified, corresponding to 392 unique ARG types classified into 32 resistance classes. The most enriched ARGs in the rodent cecal microbiome were associated with multidrug resistance, followed by glycopeptide and elfamycin antibiotics. Procrustes analysis demonstrated a correlation between the structure of the microbial community and the resistome. Metagenomic assembly-based host tracking indicated that most ARG-carrying contigs originated from the bacterial family Oscillospiraceae. Additionally, 130 ARGs showed significant correlations with mobile genetic elements. These findings provide new insights into the cecal microbiota and the prevalence of ARGs across five rodent species. Future research on a wider range of wild rodent species carrying ARGs will further elucidate the mechanisms underlying the transmission of antimicrobial resistance.

Meta-analysis of the prevalence of Giardia duodenalis in sheep and goats in China.

Giardia duodenum (G. duodenalis) can cause giardiasis and infect a variety of hosts. So far, there have been no detailed data regarding the positive rate of G. duodenalis in sheep and goats in China. Here, a systematic literature review was carried out to investigate the epidemiology of G. duodenalis in sheep and goats in China. To perform the meta-analysis, the databases CNKI, VIP, WanFang, PubMed, Web of science and ScienceDirect were employed for screening studies related to the prevalence of G. duodenalis in sheep and goats in China. The total prevalence of G. duodenalis in sheep and goats was estimated to be 7.00% (95% CI: 4.00-10.00). In the age subgroup, the prevalence of G. duodenalis in sheep and goats of >12 months (11.29%; 95% CI: 8.08-14.97) was higher than that in sheep and goats of ≤12 months (7.57%; 95% CI: 3.95-12.24). An analysis based on seasons showed that the prevalence of G. duodenalis in sheep and goats was higher in summer (11.90%; 95% CI: 0.50-35.05) than that in other seasons. The prevalence of G. duodenalis in sheep and goats after 2016 was 8.57% (95% CI: 5.34-11.79), which was higher than others. The highest prevalence of G. duodenalis in sheep and goats was 13.06% (95% CI: 6.26-19.86) recorded in Southwestern China. The prevalence of Giardia infection in sheep (7.28%; 95% CI: 2.30-14.73) was higher than that in goats (5.43%; 95% CI: 2.73-8.98). The NOAA's National Center for Environmental Information (https://gis.ncdc.noaa.gov/maps/ncei/cdo/monthly) was used to extract relevant geoclimatic data (latitude, longitude, elevation, temperature, precipitation, humidity, and climate). By analyzing the data of each subgroup, it was shown that region, genetype, and climate were potential risk factors for giardiasis prevalence in sheep and goats. Based on the analysis of common factors and geographical factors, it is recommended to strengthen effective management measures (e.g. ventilation and disinfection in warm and humid areas) and formulate relevant policies according to local conditions. Breeders should strengthen the detection of G. duodenalis in sheep and goats, customize corresponding control measures according to the diet and living habits of sheep and goats, and strengthen the protection of sheep and lamb calves, so as to reduce the incidence rate and reduce the economic loss of China's animal husbandry.

Efficacy and safety of immune checkpoint inhibitors combined with recombinant human endostatin and chemotherapy as the first-line treatment of advanced non-small-cell lung cancer.

Aim: To assess the efficacy and safety of combination of PD-1 inhibitors, recombinant human endostatin (Rh-endostatin) and chemotherapy as first-line treatment for advanced non-small-cell lung cancer (NSCLC). Methods: A total of 100 patients with advanced NSCLC were retrospectively reviewed and analyzed (58 in the group receiving PD-1 inhibitors plus Rh-endostatin and chemotherapy; 42 in the group receiving Rh-endostatin and chemotherapy). The primary end point was progression-free survival. Results: Patients in the group receiving PD-1 inhibitors plus Rh-endostatin and chemotherapy had significantly improved progression-free survival (10.2 vs 6.5 months; p < 0.001) and objective response rate (67.2 vs 42.9%; p = 0.015), with acceptable toxicity. Conclusion: Our study showed the superiority of combination therapy of PD-1 inhibitors and Rh-endostatin as first-line treatment for advanced NSCLC.

This study retrospectively analyzed the effectiveness and safety of PD-1 inhibitors combined with recombinant human endostatin (Rh-endostatin) and chemotherapy as first-line treatment for advanced non-small-cell lung cancer. Among them, 58 patients received a PD-1 inhibitor combined with Rh-endostatin and chemotherapy (treatment group), and 42 patients received Rh-endostatin combined with chemotherapy (control group). Patients in the treatment group had a significantly improved objective response rate (67.2 vs 42.9%; p = 0.015) and prolonged survival without their disease getting worse (10.2 vs 6.5 months; p < 0.001). No significant differences were found in the adverse events between the two groups.

Effect of mechanical thrombectomy with and without intravenous thrombolysis on the functional outcome of patients with different degrees of thrombus perviousness.

PURPOSE: This study aimed to investigate the long-term functional outcome of patients with different degrees of thrombus perviousness (TP) undergoing mechanical thrombectomy alone and those undergoing combined intravenous thrombolysis (IVT) plus mechanical thrombectomy. METHODS: We conducted a retrospective analysis of consecutive patients with acute ischemic stroke due to large vessel occlusion who underwent mechanical thrombectomy alone or bridging therapy between January 2016 and October 2020. TP was quantified by thrombus attenuation increase (TAI) on admission computed tomography angiography compared with non-contrast computed tomography. After dichotomization of TAI as higher or lower perviousness, Fisher exact tests were performed to estimate the associations of different therapies with favorable functional outcomes [Modified Ranking Scale score at 90 days (90-day mRS) of 0 to 2]. RESULTS: A total of 73 patients were included in our study. 35 (47.9%) thrombi were classified as higher-perviousness clots with TAI of ≥ 24 HU, and the other 38 thrombi were lower-perviousness clots. A favorable outcome with a 90-day mRS of 0 to 2 was observed in 32 patients. In patients with thrombi of lower perviousness, favorable outcome was more common in the bridging therapy group than in the thrombectomy-alone group (p = 0.013), whereas in patients with thrombi of higher perviousness, the long-term neurological outcome did not significantly differ between two therapy groups (p = 0.094). CONCLUSION: Patients with thrombi of lower perviousness were recommended to undergo intravenous alteplase followed by endovascular thrombectomy, and those with thrombi of higher perviousness could undergo thrombectomy alone.

Predictive value of infiltrating tumor border configuration of rectal cancer on MRI.

BACKGROUND: Infiltrating tumor border configuration (iTBC) is assessed by postoperative pathological examination, thus, is not helpful for preoperative treatment strategies. The study aimed to detect iTBC by magnetic resonance imaging (MRI) and evaluate its predictive value. MATERIALS AND METHODS: A total of 153 patients with rectal cancer were retrospectively analyzed. Clinicopathological and MRI data mainly including tumor border configuration (TBC) on MRI, MRI-detected extramural vascular invasion (MEMVI), tumor length, tumor growth pattern, maximal extramural depth, pathology-proven lymph node metastasis (PLN) and pathology-proven extramural vascular invasion (PEMVI) were analyzed. The correlation of MRI factors with PEMVI and PLN was analyzed by univariate and multivariate logistic regression analyses. The nomograms were established based on multivariate logistic regression analysis and were confirmed by Bootstrap self-sampling. The receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) were used to evaluate the diagnostic efficiency. RESULTS: Fifty cases of PEMVI and 48 cases of PLN were found. Forty cases of PEMVI and 34 cases of PLN in 62 cases of iTBC were also found. iTBC, MEMVI and maximal extramural depth were significantly associated with PEMVI and PLN (P < 0.05). iTBC (odds ratio = 3.84 and 3.02) and MEMVI (odds ratio = 7.27 and 3.22) were independent risk factors for PEMVI and PLN. The C-indices of the two nomograms for predicting PEMVI and PLN were 0.863 and 0.752, respectively. The calibration curves and ROC curves of the two nomograms showed that the correlation between the predicted and the actual incidence of PEMVI and PLN was good. The AUCs of iTBC for predicting PEMVI and PLN were 0.793 (95% CI: 0.714-0.872) and 0.721 (95% CI: 0.632-0.810), respectively. The DeLong test showed that the predictive efficiency of the nomogram in predicting PEMVI was better than that of iTBC (P = 0.0009) and MEMVI (P = 0.0095). CONCLUSION: iTBC and MEMVI are risk factors for PEMVI and pelvic lymph node metastasis. The nomograms based on iTBC show a good performance in predicting PEMVI and pelvic lymph node metastasis, possessing a certain clinical reference value. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Beijing Friendship Hospital, and individual consent was waived for this retrospective analysis.

Performance of Six Clinical Physiological Scoring Systems in Predicting In-Hospital Mortality in Elderly and Very Elderly Patients with Acute Upper Gastrointestinal Bleeding in Emergency Department.

Background and Objectives: The aim of this study is to compare the performance of six clinical physiological-based scores, including the pre-endoscopy Rockall score, shock index (SI), age shock index (age SI), Rapid Acute Physiology Score (RAPS), Rapid Emergency Medicine Score (REMS), and Modified Early Warning Score (MEWS), in predicting in-hospital mortality in elderly and very elderly patients in the emergency department (ED) with acute upper gastrointestinal bleeding (AUGIB). Materials and Methods: Patients older than 65 years who visited the ED with a clinical diagnosis of AUGIB were enrolled prospectively from July 2016 to July 2021. The six scores were calculated and compared with in-hospital mortality. Results: A total of 336 patients were recruited, of whom 40 died. There is a significant difference between the patients in the mortality group and survival group in terms of the six scoring systems. MEWS had the highest area under the curve (AUC) value (0.82). A subgroup analysis was performed for a total of 180 very elderly patients (i.e., older than 75 years), of whom 27 died. MEWS also had the best predictive performance in this subgroup (AUC, 0.82). Conclusions: This simple, rapid, and obtainable-by-the-bed parameter could assist emergency physicians in risk stratification and decision making for this vulnerable group.

Efficacy and safety analyses of epidermal growth factor receptor tyrosine kinase inhibitors combined with chemotherapy in the treatment of advanced non-small-cell lung cancer with an EGFR/TP53 co-mutation.

PURPOSE: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with cytotoxic chemotherapy are highly effective in the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations. The purpose of this study is to evaluate the efficacy and safety of this combination in advanced NSCLC patients with an EGFR/TP53 co-mutation. METHODS: Ninety-five advanced NSCLC patients with an EGFR/TP53 co-mutation were enrolled in this study. Treatments with either EGFR-TKI monotherapy (T group, n = 61) or EGFR-TKI combined with chemotherapy (TC group, n = 34) were evaluated in relation to objective response rate (ORR), disease control rate (DCR), median time to progression (TTP), and median overall survival (OS). RESULTS: There were no statistically significant differences in DCR between the treatment groups. The ORR was significantly improved in the TC group versus the T group (55.9% vs. 34.4%, P = 0.042). A higher median TTP was noted in TC group compared with T group (16.1 vs. 11.1 months, P = 0.002). Patients without brain metastases in TC group had a longer median OS than in T group (48.4 vs. 28.8 months, P = 0.003). However, there was a non-significant trend towards longer OS in TC group in the entire cohort (36.9 vs. 28.2 months, P = 0.078). Cox multivariate regression analysis showed that clinical stage, brain metastases, EGFR21 L858R mutation, and T790M status at first progression were independent risk factors for OS. However, the incidence of grade 3 or higher adverse events were higher in the TC group than in the T group (32.4% vs. 13.1%, P = 0.025). CONCLUSION: Our study indicates that EGFR-TKIs combined with chemotherapy could significantly improve the ORR and TTP of advanced NSCLC patients with an EGFR/TP53 co-mutation. Combination therapy may be a promising treatment for advanced NSCLC patients with an EGFR/TP53 co-mutation without brain metastases.

Surprising Hydrophobic Polymer Surface with a High Content of Hydrophilic Polar Groups.

The wetting property of a solid surface has been a hotspot for centuries, and many studies suggest that the hydrophobicity is highly related to the polar components. However, the underlying mechanism of polar moieties on the hydrophobicity remains unclear. Here, we tailor the surface polar moieties of epoxy resin (EP) by ozone modification and assess their wetting properties. Our results show that, for the modified EP with more (60.54%) polar moieties, the polar effect on hydrophobicity cannot be empirically observed. To reveal the underlying mechanism, the absorption parameters, including equilibrium distance, adsorption radius, and effective adsorption sites for water on EP before and after ozone treatment, are calculated on the basis of molecular simulations. After ozone modification, the equilibrium distance (from 1.95 to 1.70 Å), adsorption radius (from 3.80 to 4.50 Å), and effective adsorption sites (from 1 to 2) change slightly and the EP surface remains hydrophobic, although the polar groups significantly increase. Therefore, it is concluded that the wetting properties of solid surfaces are dominated by the equilibrium distance, adsorption radius, and effective adsorption sites for water on solids, and the nonlinear relationship between polar groups and hydrophilicity is clarified.

Modified biochar improves the storage capacity and adsorption affinity of organic phosphorus in soil.

The loss of soil organic phosphorus can easily cause water eutrophication. In order to effectively reduce the loss of soil organic phosphorus, this manuscript investigated the adsorption of soil organic phosphorus by lanthanum modified biochar (BC), traditional adsorbent gypsum (GY) and zeolite (ZE) by taking phytic acid as the representative. The adsorption isotherm model and kinetic models were used to fit the phosphorus absorption characteristics of the adsorbents. The effects of initial pH and temperature on the adsorption capacity were discussed, and the adsorption mechanism of each adsorbent was explained by means of FTIR and XRD. The results showed that the adsorption capacity of phytate phosphorus followed the trend of BCTS > GYTS > ZETS > TS (soil), and the maximum phosphorus adsorption capacity obtained from Langmuir isotherm for treatment with BCTS was 2.836 mg g-1, and the treatment had the strongest affinity for phytate phosphorus and also the ability to store phosphorus. The adsorption process fits well with Langmuir isotherm equation and pseudo-second-order kinetic equation, and the adsorption behavior of phytate phosphorus was mainly controlled by the chemisorption of monolayer. When the concentration of phytate phosphorus was 100 mg L-1, percentage of modified biochar added to the soil was 3% and the pH was 6, the adsorption capacity reached the maximum, and the maximum adsorption capacity was 2.000 mg g-1. The results of FTIR and XRD characterization showed that complexation was the main adsorption mechanism. In this study, the combination of modified biochar and soil phytate phosphorus can provide a good theoretical basis for reducing the loss of soil organic phosphorus.

Does medical disparity exist while treating severe mental illness patients with acute appendicitis in emergency departments? A real-world database study.

BACKGROUND: Patients with severe mental illness (SMI) have a shorter life expectancy and have been considered by the World Health Organization (WHO) as a vulnerable group. As the causes for this mortality gap are complex, clarification regarding the contributing factors is crucial to improving the health care of SMI patients. Acute appendicitis is one of the most common indications for emergency surgery worldwide. A higher perforation rate has been found among psychiatric patients. This study aims to evaluate the differences in appendiceal perforation rate, emergency department (ED) management, in-hospital outcomes, and in-hospital expenditure among acute appendicitis patients with or without SMI via the use of a multi-centre database. METHODS: Relying on Chang Gung Research Database (CGRD) for data, we selectively used its data from January 1st, 2007 to December 31st, 2017. The diagnoses of acute appendicitis and SMI were confirmed by combining ICD codes with relevant medical records. A non-SMI patient group was matched at the ratio of 1:3 by using the Greedy algorithm. The outcomes were appendiceal perforation rate, ED treatment, in-hospital outcome, and in-hospital expenditure. RESULTS: A total of 25,766 patients from seven hospitals over a span of 11 years were recruited; among them, 11,513 were excluded by criteria, with 14,253 patients left for analysis. SMI group was older (50.5 vs. 44.4 years, p < 0.01) and had a higher percentage of females (56.5 vs. 44.4%, p = 0.01) and Charlson Comorbidity Index. An analysis of the matched group has revealed that the SMI group has a higher unscheduled 72-hour revisit to ED (17.9 vs. 10.4%, p = 0.01). There was no significant difference in appendiceal perforation rate, ED treatment, in-hospital outcome, and in-hospital expenditure. CONCLUSIONS: Our study demonstrated no obvious differences in appendiceal perforation rate, ED management, in-hospital outcomes, and in-hospital expenditure among SMI and non-SMI patients with acute appendicitis. A higher unscheduled 72-hour ED revisit rate prior to the diagnosis of acute appendicitis in the SMI group was found. ED health providers need to be cautious when it comes to SMI patients with vague symptoms or unspecified abdominal complaints.

RPL35A is a key promotor involved in the development and progression of gastric cancer.

BACKGROUND: RPL35A has been reported to work as a biomarker in tumor angiogenesis. However, little work has been performed on the expression level and functional importance of RPL35A in gastric cancer (GC). METHODS: The protein expression level of RPL35A was detected by immunohistochemical staining and western blot analysis. The Celigo cell counting assay was used to assess cell proliferation. Both the wound healing assay and the transwell assay were conducted to evaluate cell migration. Flow cytometric analysis was utilized to detect cell apoptosis and cell cycle. A mouse xenograft model was constructed for in vivo experiments. RESULTS: The results demonstrated that RPL35A expression was abundantly up-regulated in GC and positively related to tumor infiltrate. In addition, RPL35A knockdown could significantly suppress cell proliferation, migration, enhance apoptosis and arrest cell cycle. The in vivo study also verified the inhibitory effects of RPL35A knockdown on GC tumorigenesis. CONCLUSIONS: The above mentioned results indicated that the knockdown of RPL35A might be a considerable therapeutic strategy for the treatment of gastric cancer.

Experimental Imaging Study of Encephalomalacia Fluid-Attenuated Inversion Recovery (FLAIR) Hyperintense Lesions in Posttraumatic Epilepsy.

This study introduced new MRI techniques such as neurite orientation dispersion and density imaging (NODDI); NODDI applies a three-compartment tissue model to multishell DWI data that allows the examination of both the intra- and extracellular properties of white matter tissue. This, in turn, enables us to distinguish the two key aspects of axonal pathology-the packing density of axons in the white matter and the spatial organization of axons (orientation dispersion (OD)). NODDI is used to detect possible abnormalities of posttraumatic encephalomalacia fluid-attenuated inversion recovery (FLAIR) hyperintense lesions in neurite density and dispersion. Methods. 26 epilepsy patients associated with FLAIR hyperintensity around the trauma encephalomalacia region were in the epilepsy group. 18 posttraumatic patients with a FLAIR hyperintense encephalomalacia region were in the nonepilepsy group. Neurite density and dispersion affection in FLAIR hyperintense lesions around encephalomalacia were measured by NODDI using intracellular volume fraction (ICVF), and we compare these findings with conventional diffusion MRI parameters, namely, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Differences were compared between the epilepsy and nonepilepsy groups, as well as in the FLAIR hyperintense part and in the FLAIR hypointense part to try to find neurite density and dispersion differences in these parts. Results. ICVF of FLAIR hyperintense lesions in the epilepsy group was significantly higher than that in the nonepilepsy group (P < 0.001). ICVF reveals more information of FLAIR(+) and FLAIR(-) parts of encephalomalacia than OD and FA and ADC. Conclusion. The FLAIR hyperintense part around encephalomalacia in the epilepsy group showed higher ICVF, indicating that this part may have more neurite density and dispersion and may be contributing to epilepsy. NODDI indicated high neurite density with the intensity of myelin in the FLAIR hyperintense lesion. Therefore, NODDI likely shows that neurite density may be a more sensitive marker of pathology than FA.

What is the impact of the COVID-19 pandemic on residency training: a systematic review and analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has greatly affected medical education in addition to clinical systems. Residency training has probably been the most affected aspect of medical education during the pandemic, and research on this topic is crucial for educators and clinical teachers. The aim of this study was to understand the effect of the COVID-19 pandemic comprehensively through a systematic review and analysis of related published articles. METHODS: A systematic review was conducted based on a predesigned protocol. We searched MEDLINE and EMBASE databases until November 30, 2020, for eligible articles. Two independent reviewers extracted data by using a customized form to record crucial information, and any conflicts between the two reviewers were resolved through discussion with another independent reviewer. The aggregated data were summarized and analyzed. RESULTS: In total, 53 original articles that investigated the effect of the COVID-19 pandemic on residency training were included. Studies from various regions were included in the research, with the largest percentage from the United States (n = 25, 47.2%). Most of these original articles were questionnaire-based studies (n = 44, 83%), and the research target groups included residents (79.55%), program directors (13.64%), or both (6.82%). The majority of the articles (n = 37, 84.0%) were published in countries severely affected by the pandemic. Surgery (n = 36, 67.92%) was the most commonly studied field. CONCLUSIONS: The COVID-19 pandemic has greatly affected residency training globally, particularly surgical and interventional medical fields. Decreased clinical experience, reduced case volume, and disrupted education activities are major concerns. Further studies should be conducted with a focus on the learning outcomes of residency training during the pandemic and the effectiveness of assisted teaching methods.

Sarcopenia is a useful risk stratification tool to prognosticate splenic abscess patients in the emergency department.

BACKGROUND/PURPOSE: Splenic abscess is a life-threatening surgical emergency which requires early diagnosis and intervention to maximize patient outcomes. This can be achieved through accurate risk stratification in the emergency department (ED). Sarcopenia refers to an age-related loss of skeletal muscle mass and strength that is accompanied by major physiologic and clinical ramifications, and often signifies decreased physiologic reserves. It is associated with poor clinical outcomes in sepsis, acute respiratory failure, oncological surgery, and liver transplantation. This study evaluates the utility of sarcopenia as a radiological stratification tool to predict in-hospital mortality of splenic abscess patients in the ED. This will assist emergency physicians, internists and surgeons in rapid risk stratification, assessing treatment options, and communicating with family members. METHODS: 99 adult patients at four training and research hospitals who had undergone an abdominal contrast computed tomography scan in the ED with the final diagnosis of splenic abscess from January 2004 to November 2017 were recruited. Evaluation for sarcopenia was performed via calculating the psoas cross-sectional area at the level of the third lumbar vertebra and normalising for height, before checking it against pre-defined values. Univariate analyses were used to evaluate the differences between survivors and non-survivors. Sensitivity, specificity, and predictive values of the presence of sarcopenia in predicting in-hospital mortality were calculated. Kaplan-Meier methods, log-rank test, and Cox proportional hazards model were also performed to examine survival between groups with sarcopenia versus non-sarcopenia. RESULTS: Splenic abscess patients with sarcopenia were 7.56 times more at risk of in-hospital mortality than those without sarcopenia (multivariate-adjusted HR: 7.56; 95% CI: 1.55-36.93). Presence of sarcopenia was found to have 84.62% sensitivity and 96.49% negative predictive value in predicting mortality. CONCLUSION: Sarcopenia is associated with poor prognoses of in-hospital mortality in patients with splenic abscess presenting to the ED. We recommend its use in the ED to rapidly risk stratify and predict outcome to guide treatment strategies.

Tuling Wendan Decoction combined with flunarizine in the treatment of migraine patients and the effect of intervention on serum cyclooxygenase-2, endothelin-1 and nitric oxide.

This experiment aimed to explore the curative effect of Tuling Wendan Decoction combined with flunarizine on migraine patients and the intervention effect on serum cyclooxygenase-2 (COX-2), endothelin-1 (ET-1), nitric oxide(NO) levels. For this purpose, from January 2019 to January 2020, 96 patients with migraine in our hospital were selected as the research object. Using a simple randomization method, patients who meet the criteria were assigned 1:1, and each patient was assigned a random number, of which the number 1 to 48 were the observation group, and the number 49 to 96 were the control group. The control group was treated with flunarizine, and the observation group was treated with Tuling Wendan Decoction combined with flunarizine. Comparing the efficacy, incidence of adverse reactions, the incidence of headache, cerebral blood flow rate [basal artery (BA), vertebral artery (VA), middle cerebral artery (MCA)], vascular endothelial function (serum COX-2, ET-1, NO levels), neurological function [5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), calcitonin gene-related peptide (CGRP)] before treatment, 4 weeks and 8 weeks after treatment between the two groups. The results for efficacy showed that after 8 weeks of treatment, the total effective rate of the observation group (93.75%) was higher than that of the control group (77.08%, P<0.05). In regards to the situation of headache attack, the number of headache attacks, duration, pain degree and accompanying symptom scores of the observation group after 4 weeks and 8 weeks of treatment were lower than those of the control group (P<0.05). Results of cerebral blood flow velocity showed that the blood flow velocity of BA, VA, MCA in the observation group was lower than that in the control group after 4 and 8 weeks of treatment (P<0.05). Vascular endothelial function results indicated that the serum COX-2 and ET-1 levels of the observation group were lower than those of the control group after 4 weeks and 8 weeks of treatment, and the serum NO levels were higher than that of the control group (P<0.05). The serum BDNF and CGRP levels of the observation group were lower than those of the control group after 4 weeks and 8 weeks of treatment, and the serum 5-HT levels were higher than the control group (P<0.05). The incidence of adverse reactions between the two groups was not statistically significant (P>0.05). It was concluded that Tuling Wendan Decoction combined with flunarizine is the first treatment for migraine, with definite curative effect and can effectively improve the onset of headache, reduce the speed of cerebral blood flow, regulate vascular endothelial function and nerve function, and ensure safety.