Endoscopy for acute upper gastrointestinal bleeding: a protocol for systematic review and network meta-analysis of randomized controlled trials.

Background: Previous studies have reached mixed conclusions regarding the timing of endoscopic approaches for managing individuals with acute upper gastrointestinal bleeding (AUGIB). Therefore, the authors performed a protocol for systematic review and meta-analysis to assess the efficacy of various timing endoscopic approaches in managing individuals with AUGIB. Methods: The authors will search multiple databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure, VIP Database, Wanfang Database, WHO International Clinical Trials Registry Platform, and Chinese Clinical Trial Register. The search will cover the entire duration, starting from the establishment of these databases until July 2023. The selection criteria will focus on randomized controlled trials that assess the efficacy of endoscopy with varying timing in managing patients with AUGIB. The primary outcomes will include primary hemostasis and inpatient death. The secondary outcomes will include recurrent bleeding, need for surgical intervention, admission to the ICU, blood transfusion needs, and duration of hospitalization. Two reviewers will select the studies, extract data, and assess the risk of bias. A Bayesian approach will be used to conduct a network meta-analysis. Results: The results of this systematic review and meta-analysis will be published in peer-reviewed journals. Conclusion: This network meta-analysis provides comprehensive evidence of different timing endoscopic approaches for managing individuals with AUGIB.

Discovery of baloxavir sodium as a novel anti-CCHFV inhibitor: Biological evaluation of in vitro and in vivo.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic bunyavirus with a fatality rate of up to 40%. Currently, there are no licensed antiviral drugs for the treatment of CCHF; thus, the World Health Organization (WHO) listed the disease as a priority. A unique viral transcription initiation mechanism called "cap-snatching" is shared by influenza viruses and bunyaviruses. Thus, we tested whether baloxavir (an FDA-approved anti-influenza drug that targets the "cap-snatching" mechanism) could inhibit CCHFV infection. In cell culture, baloxavir acid effectively inhibited CCHFV infection and targeted CCHFV RNA transcription/replication. However, it has weak oral bioavailability. Baloxavir marboxil (the oral prodrug of baloxavir) failed to protect mice against a lethal dose challenge of CCHFV. To solve this problem, baloxavir sodium was synthesized owing to its enhanced aqueous solubility and pharmacokinetic properties. It consistently and significantly improved survival rates and decreased tissue viral loads. This study identified baloxavir sodium as a novel scaffold structure and mechanism of anti-CCHF compound, providing a promising new strategy for clinical treatment of CCHF after further optimization.

Crucial role played by CK8+ cells in mediating alveolar injury remodeling for patients with COVID-19.

The high risk of SARS-CoV-2 infection and reinfection and the occurrence of post-acute pulmonary sequelae have highlighted the importance of understanding the mechanism underlying lung repair after injury. To address this concern, comparative and systematic analyses of SARS-CoV-2 infection in COVID-19 patients and animals were conducted. In the lungs of nine patients who died of COVID-19 and one recovered from COVID-19 but died of unrelated disease in early 2020, damage-related transient progenitor (DATP) cells expressing CK8 marker proliferated significantly. These CK8+ DATP cells were derived from bronchial CK5+ basal cells. However, they showed different cell fate toward differentiation into type I alveolar cells in the deceased and convalescent patients, respectively. By using a self-limiting hamster infection model mimicking the dynamic process of lung injury remodeling in mild COVID-19 patients, the accumulation and regression of CK8+ cell marker were found to be closely associated with the disease course. Finally, we examined the autopsied lungs of two patients who died of infection by the recent Omicron variant and found that they only exhibited mild pathological injury with no CK8+ cell proliferation. These results indicate a clear pulmonary cell remodeling route and suggest that CK8+ DATP cells play a primary role in mediating alveolar remodeling, highlighting their potential applications as diagnostic markers and therapeutic targets.

Machine Learning Predictive Model for Septic Shock in Acute Pancreatitis with Sepsis.

Objective: Acute pancreatitis (AP) progresses to septic shock can be fatal. Early identification of high-risk patients and timely intervention can prevent and interrupt septic shock. By analyzing the clinical characteristics of AP with sepsis, this study uses machine learning (ML) to build a model for early prediction of septic shock within 28 days of admission, which guided emergency physicians in resource allocation and medical decision-making. Methods: This retrospective cohort study collected data from the emergency departments (EDs) of three tertiary care hospitals in China. The dataset was randomly divided into a training dataset (70%) and a testing dataset (30%). Ten ML classifiers were utilized to analyze characteristics of AP with sepsis in the training dataset upon admission. Results were evaluated through cross-validation analysis. The optimal model was then tested on the testing dataset without any parameter modifications. The ML model was evaluated using the receiver operating characteristic curve (ROC) and compared to scoring systems through the DeLong test. Results: A total of 604 AP patients with sepsis were included in this study. The auto-encoder (AE) model based on mean normalization, Pearson correlation coefficient (PCC), and recursive feature elimination (RFE) selection, achieved the highest Area Under the Curve (AUC) on the validation dataset (AUC 0.900, accuracy 0.868), with the AUC of 0.879 and accuracy of 0.790 on the testing dataset. Compared to the Sequential Organ Failure Assessment (AUC 0.741), quick Sequential Organ Failure Assessment (AUC 0.727), Acute Physiology and Chronic Health Evaluation II (AUC 0.778), and Bedside Index of Severity in Acute Pancreatitis (AUC 0.691), the AE model showed superior performance. Conclusion: The AE model outperforms traditional scoring systems in predicting septic shock in AP patients with sepsis within 28 days of admission. This assists emergency physicians in identifying high-risk patients early and making timely medical decisions.

Identification of a murder caused by brodifacoum poisoning based on clinical examinations and LC-MS/MS results.

Brodifacoum exerts its antagonistic effect against the metabolism of vitamin K, an essential component in the synthesis of blood coagulation factors. This effect ultimately hinders the blood's capacity to clot effectively, rendering it a commonly employed rodenticide. Instances of lethal poisonings are exceedingly rare owing to expeditious medical intervention and treatment. Within this report, we present a case of brodifacoum-induced homicide, wherein the patient exhibited distinct clinical examinations and symptoms. Moreover, the patient's blood sample exhibited a noteworthy brodifacoum concentration of 0.681 µg/mL even after a period of 43 days following the incident of poisoning. Although an autopsy was not conducted due to religious restrictions, we endeavor to reasonably deduce the cause of death and furnish corroborative evidence for clinical diagnosis, treatment, and forensic examination in instances involving brodifacoum poisoning.

Chinese Society of Cardiology guidelines on the diagnosis and treatment of adult fulminant myocarditis.

Fulminant myocarditis is an acute diffuse inflammatory disease of myocardium. It is characterized by acute onset, rapid progress and high risk of death. Its pathogenesis involves excessive immune activation of the innate immune system and formation of inflammatory storm. According to China's practical experience, the adoption of the "life support-based comprehensive treatment regimen" (with mechanical circulation support and immunomodulation therapy as the core) can significantly improve the survival rate and long-term prognosis. Special emphasis is placed on very early identification,very early diagnosis,very early prediction and very early treatment.

Deep spatial proteomics reveals region-specific features of severe COVID-19-related pulmonary injury.

As a primary target of severe acute respiratory syndrome coronavirus 2, lung exhibits heterogeneous histopathological changes following infection. However, comprehensive insight into their protein basis with spatial resolution remains deficient, which hinders further understanding of coronavirus disease 2019 (COVID-19)-related pulmonary injury. Here, we generate a region-resolved proteomic atlas of hallmark pathological pulmonary structures by integrating histological examination, laser microdissection, and ultrasensitive proteomics. Over 10,000 proteins are quantified across 71 post-mortem specimens. We identify a spectrum of pathway dysregulations in alveolar epithelium, bronchial epithelium, and blood vessels compared with non-COVID-19 controls, providing evidence for transitional-state pneumocyte hyperplasia. Additionally, our data reveal the region-specific enrichment of functional markers in bronchiole mucus plugs, pulmonary fibrosis, airspace inflammation, and alveolar type 2 cells, uncovering their distinctive features. Furthermore, we detect increased protein expression associated with viral entry and inflammatory response across multiple regions, suggesting potential therapeutic targets. Collectively, this study provides a distinct perspective for deciphering COVID-19-caused pulmonary dysfunction by spatial proteomics.

A rare case of respiratory failure associated with spinal cord injury caused by stabbing with scissors and a knife.

In forensic practice, spinal cord injury (SCI) resulting in death has rarely been reported. Here, we present the case of a 65-year-old woman who on admission was conscious without dyspnea or dysphagia. Physical examination revealed two sharp objects penetrating the neck: a pair of scissors lodged in the neck on the right side of the thyroid cartilage and a knife embedded in the nuchal region accompanied by minor seepage of bloody exudate. Radiography showed that the scissors and knife were retained in the cervical spine. Despite a series of medical interventions, the patient died 26 days later. METHOD: A systematic forensic autopsy was performed. RESULTS: The cause of death was confirmed to be respiratory failure associated with SCI, which was caused by the combination of scissors and a knife. CONCLUSION: Based on this case, we believe that when there are multiple causes of death, forensic pathologists should determine the primary, immediate, contributory, and other causes of death to ascertain criminal responsibility.

Development and Validation of a Rapid and Efficient Prognostic Scoring System for Sepsis Based on Oxygenation Index, Lactate and Glasgow Coma Scale.

Objective: To develop a concise scoring system for efficient and rapid assessment of sepsis prognosis applicable to emergency departments. Methods: This was a single-center retrospective cohort study of patients with sepsis. In this study, a new scoring system (oxygenation index, lactate, and Glasgow coma scale: GOL) was developed through a derivation group, and then the GOL was validated using a validation group. Multivariate logistic regression analysis was performed to investigate the relationship between GOL and 28-day adverse outcomes. The GOL was compared with the previous scoring system using receiver operating characteristic curves (ROC) and decision analysis curves. The endpoints of this study were mortality, mechanical ventilation (MV), and admission to the intensive care unit (AICU). Results: 608 patients were included in the derivation group and 213 patients in the validation group, with 131 and 42 deaths, respectively. In the validation group, lactate (Lac), oxygenation index (PaO2/FiO2), and Glasgow coma scale score (GCS), the three best performers in predicting 28-day mortality from receiver operating characteristic curves, were used to construct the GOL. The higher the GOL score, the higher the incidence of death, MV and AICU within 28 days. Multifactorial logistic regression analysis showed that when the GOL was greater than 1, it was an independent risk factor for 28-day mortality, MV, and AICU. In predicting 28-day mortality, GOL was superior to the quick Sequential Organ Failure Assessment (qSOFA), Mortality in Emergency Department Sepsis Score (MEDS), Systemic Inflammatory Response Syndrome Score (SIRS), and Modified Early Warning Score (MEWS), and was comparable to the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA). Conclusion: The GOL is a simple, rapid, and accurate method for early identification of patients at increased risk of in-hospital death from sepsis.

Prognostic value of sarcopenia in older adults with transcatheter aortic valve implantation: A systematic review and meta-analysis.

OBJECTIVE: We conducted this systematic review and meta-analysis to summarize the prevalence of sarcopenia and its impact on mortality in patients undergoing TAVI. METHOD: Medline, EMBASE, and PubMed were searched from inception to October 14, 2022 to retrieve eligible studies that assessed sarcopenia in patients undergoing TAVI. Pooled sarcopenia prevalence was calculated with 95% confidence interval (CI), and heterogeneity was estimated using the I2 test. Associations of sarcopenia with mortality of post-TAVI were expressed as hazard ratio (HR) or odds ratios (OR) and 95% CI. RESULTS: 13 studies involving 5248 patients (mean age from 78.1 to 84.9 years) undergoing TAVI were included. There were eleven studies defined sarcopenia based on loss of skeletal muscle mass index (SMI), while only two studies used low muscle mass plus low muscle strength and/or low physical performance. Overall, the pooled prevalence of sarcopenia in patients undergoing TAVI was 49% (95% CI 41%-58%). Sarcopenia was associated with an increased risk of long-term (≥1 year) mortality in patients after TAVI (HR 1.57, 95% CI 1.33-1.85, P < 0.001), with similar findings in the subgroups stratified by follow-up time, definition of sarcopenia, study location, and study design. Furthermore, the 1-, 2-, and 3-year cumulative probabilities of survival in patients with sarcopenia were significantly lower than non-sarcopenia (74.0% vs 91.0%, 68.3% vs 78.0%, and 72.6% vs 79.8%, all P < 0.05). CONCLUSIONS: Although there are substantial differences in diagnostic criteria, sarcopenia is highly prevalent in patients undergoing TAVI and its linked to increased long-term mortality after TAVI.

Potential biomarkers in hypoglycemic brain injury.

Oxidative stress is a major underlying mechanism in hypoglycemic brain injury. Several oxidative stress-related proteins were identified through previous proteomics and literature review. The aim of the present study was to evaluate the potential of these proteins as biomarkers in hypoglycemic brain injury. Forty male Sprague Dawley rats were randomly and equally divided into four groups: control, acute hypoglycemia, hypoglycemia resuscitation 24 h, and hypoglycemia resuscitation 7 days. The hypoglycemic brain injury rat model was successfully constructed according to the Auer model. Real-time fluorescent quantitative polymerase chain reaction, western blot analysis, and immunohistochemical staining were used to quantify the expression of oxidative stress-related proteins. We also verified the expression level of selected protein in the brain samples of fatal insulin overdose cases. The expression of oxidative stress-related proteins PEX1/5/12 was down-regulated in hypoglycemic brain injury (P < 0.05), while the expressions of DJ-1 and NDRG1 were up-regulated (P < 0.05). Compared with the control group, the serum oxidative stress indexes SOD and MDA in the acute hypoglycemia group were significantly different (P < 0.01). The expressions of DJ-1 and NDRG1 in the hippocampus, cortex, and hypothalamus of rats were increased (P < 0.05). The expressions of DJ-1 and NDRG1 proteins in the cortex of the autopsy samples of insulin overdose were increased (P < 0.05). Oxidative stress-related proteins showed potential value as specific molecular markers in hypoglycemic brain injury, but further confirmatory studies are needed.

The effect of externally applied traditional Chinese medicine in diabetic foot: A systematic review and meta-analysis of 34 RCTs.

AIM: This study aimed to investigate the clinical efficacy of externally applied Traditional Chinese Medicine (TCM) on diabetic foot. METHODS: We searched the China Knowledge Network (CNKI), Wanfang Database, PubMed and Web of Science from inception to July 31, 2022, to find all randomized control trials (RCTs) related to externally applied TCMs in diabetic foot treatment. Information about the total effective rate, healing rate, and healing time were extracted. In addition, the relative risk (RR)/odds ratio (OR) or standardized mean difference (SMD) and 95 % confidence interval (CI) were calculated. RESULTS: Finally, a total of 34 RCTs including 3758 patients were included in this meta-analysis. There were 5 articles that reported hydropathic compress with astrogalin, 14 articles that reported MEBO burn cream, 9 articles that reported compound cortex phellodendri liquid and 6 articles that reported Shengji Yuhong ointment. Compared with the basic treatment, the externally applied TCM (astrogalin, MEBO burn cream, compound cortex phellodendri liquid and Shengji Yuhong ointment) combined with basic treatment improved the total effective rate (RR = 1.31 [1.20, 1.42], P < 0.0001) and healing rate (RR = 1.84 [1.56, 2.17], P < 0.0001) and shortened the healing time (SMD = - 2.51 [- 3.39, - 1.63], P < 0.0001). CONCLUSION: Our systematic review and meta-analysis revealed that common TCM applied externally could significantly improve the clinical efficacy comparing to the basic treatment.

Four cases of fatal acute arsenic poisoning: histopathology, toxicology, and new trends.

Arsenic is a valuable component in tumor treatment and traditional Chinese medicine and has seen widespread use in processing, manufacturing, and agriculture. Although rare, arsenic poisoning can occur in forensic practice. Elusive pathological changes, as well as obscure clinical signs, may cause arsenic poisoning to go unrecognized. Here, we report four cases of fatal acute arsenic poisoning, with careful observation of pathological changes and collection of postmortem specimens for arsenic concentration analysis. Additionally, we reviewed six cases of fatal arsenic poisoning in the past 20 years. In the present study, microvesicular steatosis in the peripheral areas of the hepatic lobules and acute splenitis were observed, which are rare findings in acute arsenic poisoning. This study summarizes the histopathological features of arsenic poisoning and presents data on arsenic distribution. Arsenic concentrations in the liver and kidneys can increase the reliability of identifying arsenic poisoning. Furthermore, in traditional Chinese medicine-related deaths, arsenic poisoning needs more attention.

Prognostic value of temporal muscle thickness, a novel radiographic marker of sarcopenia, in patients with brain tumor: A systematic review and meta-analysis.

Sarcopenia has been identified as a prognostic factor among certain types of cancer. However, it is unclear whether there is prognostic value of temporalis muscle thickness (TMT), a potential surrogate for sarcopenia, in adults patients with brain tumors. Therefore, we searched the Medline, Embase, and PubMed to systematically review and meta-analyze the relationship between TMT and overall survival, progression-free survival, and complications in patients with brain tumors and the hazard ratio (HR) or odds ratios (OR), and 95% confidence interval (CI) were evaluated. The quality in prognostic studies (QUIPS) instrument was employed to evaluate study quality. Nineteen studies involving 4570 patients with brain tumors were included for qualitative and quantitative analysis. Meta-analysis revealed thinner TMT was associated with poor overall survival (HR, 1.72; 95% CI, 1.45-2.04; P < 0.01) in patients with brain tumors. Sub-analyses showed that the association existed for both primary brain tumors (HR, 2.02; 95% CI, 1.55-2.63) and brain metastases (HR, 1.39; 95% CI, 1.30-1.49). Moreover, thinner TMT also was the independent predictor of progression-free survival in patients with primary brain tumors (HR, 2.88; 95% CI, 1.85-4.46; P < 0.01). Therefore, to improve clinical decision making it is important to integrate TMT assessment into routine clinical settings in patients with brain tumors.

Hybridoma-derived neutralizing monoclonal antibodies against Beta and Delta variants of SARS-CoV-2 in vivo.

Neutralizing monoclonal antibodies (mAb) are a major therapeutic strategy for the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The continuous emergence of new SARS-CoV-2 variants worldwide has increased the urgency for the development of new mAbs. In this study, we immunized mice with the receptor-binding domain (RBD) of the SARS-CoV-2 prototypic strain (WIV04) and screened 35 RBD-specific mAbs using hybridoma technology. Results of the plaque reduction neutralization test showed that 25 of the mAbs neutralized authentic WIV04 strain infection. The 25 mAbs were divided into three categories based on the competitive enzyme-linked immunosorbent assay results. A representative mAb was selected from each category (RD4, RD10, and RD14) to determine the binding kinetics and median inhibitory concentration (IC50) of WIV04 and two variants of concern (VOC): B.1.351 (Beta) and B.1.617.2 (Delta). RD4 neutralized the B.1.617.2 variant with an IC50 of 2.67 â€‹ng/mL; however, it completely lost neutralizing activity against the B.1.351 variant. RD10 neutralized both variants with an IC50 exceeding 100 â€‹ng/mL; whereas RD14 neutralized two variants with a higher IC50 (>1 â€‹mg/mL). Animal experiments were performed to evaluate the protective effects of RD4 and RD10 against various VOC infections. RD4 could protect Adv-hACE2 transduced mice from B.1.617.2 infection at an antibody concentration of 25 â€‹mg/kg, while RD10 could protect mice from B.1.351 infection at an antibody concentration of 75 â€‹mg/kg. These results highlight the potential for future modifications of the mAbs for practical use.

Inferior vena cava injury during percutaneous vertebroplasty: a rare cause of fatal pulmonary thromboembolism.

Fatal pulmonary thromboembolism (PTE) following percutaneous vertebroplasty is rare in medical practice. Here, we report the case of a 70-year-old woman who suffered from lumbago with lower extremity pain and lameness and for whom lumbar osteoporotic vertebral compression fractures (L4, L5) were seen on MRI examination. Percutaneous vertebroplasty and posterior vertebral lamina fenestration discectomy were performed. One day later, her condition deteriorated after defecation, and she died suddenly. Pulmonary thromboembolus and deep venous thrombosis in the inferior vena cava were the major findings at forensic autopsy. Due to the rather uncommon components of the thromboembolus (chondrocytes, calcium deposits, and collagen fibers), the pulmonary thromboembolism was attributed to deep venous thrombosis in the inferior vena cava, which was injured during percutaneous vertebroplasty. The present study highlights the conclusion that pulmonary thromboembolism is a rare complication of percutaneous vertebroplasty that should attract the attention of clinical physicians and forensic pathologists.

Contribution of Trp63CreERT2-labeled cells to alveolar regeneration is independent of tuft cells.

Viral infection often causes severe damage to the lungs, leading to the appearance of ectopic basal cells (EBCs) and tuft cells in the lung parenchyma. Thus far, the roles of these ectopic epithelial cells in alveolar regeneration remain controversial. Here, we confirm that the ectopic tuft cells are originated from EBCs in mouse models and COVID-19 lungs. The differentiation of tuft cells from EBCs is promoted by Wnt inhibition while suppressed by Notch inhibition. Although progenitor functions have been suggested in other organs, pulmonary tuft cells don't proliferate or give rise to other cell lineages. Consistent with previous reports, Trp63CreERT2 and KRT5-CreERT2-labeled ectopic EBCs do not exhibit alveolar regeneration potential. Intriguingly, when tamoxifen was administrated post-viral infection, Trp63CreERT2 but not KRT5-CreERT2 labels islands of alveolar epithelial cells that are negative for EBC biomarkers. Furthermore, germline deletion of Trpm5 significantly increases the contribution of Trp63CreERT2-labeled cells to the alveolar epithelium. Although Trpm5 is known to regulate tuft cell development, complete ablation of tuft cell production fails to improve alveolar regeneration in Pou2f3-/- mice, implying that Trpm5 promotes alveolar epithelial regeneration through a mechanism independent of tuft cells.

Factors That May Impact the Noninvasive Measurement of Central Blood Pressure Compared to Invasive Measurement: The MATCHY Study.

Calibration affects central blood pressure (BP) estimation accuracy. Factors influencing the accuracy of noninvasive central BP measurement, type of calibration method implemented (systolic/diastolic BP or mean/diastolic BP), and type of BP measurement device used (devices using the transfer function method, directly measurement from the carotid artery, and the transfer function-like method), were investigated. Fifty participants (aged 62.4 ± 8.9 years) without overt heart diseases were recruited. Invasive aortic and radial BP was measured. Simultaneously, noninvasive central BP was measured using three types of devices. The mean invasive aortic BP was 127 ± 19/95 ± 14 mmHg. Noninvasive central BP tended to be slightly lower than invasive BP, though without statistical significance. The type of calibration method did not significantly influence the noninvasive cSBP measurements (p ≥ 0.24). Results from cuff-based devices were significantly lower than invasive measurements (p = 0.04). Multiple regression analyses showed that gender was significantly correlated with the accuracy of noninvasive cSBP measurement. In conclusion, noninvasive cSBP measurements are comparable to invasive measurements but might underestimate true cSBP. The type of device may affect the accuracy of measurement. Either of the two calibration methods is acceptable.

Forensic identification of a fatal snakebite from Bungarus multicinctus (Chinese krait) by pathological and toxicological findings: a case report.

Bungarus multicinctus (B. multicinctus) is one of the top ten venomous snakes in China, ranking first in lethality at 26.9-33.3%. However, to our knowledge, no forensic autopsy-related cases of death from B. multicinctus bite poisoning have been reported. There are surprisingly few reported cases of death from poisoning by other species of neurotoxic snakes. Neurotoxic snake venom is often highly toxic, and death can quickly occur when bitten in the wild if victims are not taken to a doctor in time. We presented a case of an adult female in Fujian Province of China who was bitten by a poisonous snake while digging for bamboo shoots in the mountains and died from the bite of B. multicinctus confirmed by enzyme-linked immunosorbent assays (ELISA) results. The autopsy's results, histopathological findings, and ELISA results reported here can be helpful for future forensic practice in B. multicinctus venom poisoning; we also briefly review the pathological changes of neurotoxin poisoning, which may be useful in other types of neurotoxin snake venom poisoning.