Most immune-related adverse event (irAE) associated with immune checkpoint inhibitors (ICIs) resulted from excessive immune response against normal organs. The severity, timing, and organs affected by these events were often unpredictable. Adverse reactions could cause treatment delays or interruptions, in rare cases, pose a life-threatening risk. The mechanisms underlying irAE involved immune cell dysregulation, imbalances in inflammatory factor expression, alterations in autoantibodies and complement activation, even dysbiosis of intestinal microorganisms. However, the mechanisms of irAE occurrence might differ slightly among organs due to variations in their structures and the functions of resident immune cells. Future research should focus on the development of targeted drugs for the prevention or treatment of irAE based on the mechanisms by which irAE occurs in different organs. A deeper understanding of the mechanisms underlying irAE occurrence would aid clinicians in effectively utilizing ICIs and provide valuable guidance for their clinical application.
Antimicrobial resistance is a rigorous health issue around the world. Because of the short turn-around-time and broad pathogen spectrum, culture-independent metagenomic next-generation sequencing (mNGS) is a powerful and highly efficient tool for clinical pathogen detection. The increasing question is whether mNGS is practical in the prediction of antimicrobial susceptibility. This review summarizes the current mNGS-based antimicrobial susceptibility testing technologies. The critical determinants of mNGS-based antibacterial resistance prediction have been comprehensively analyzed, including antimicrobial resistance databases, sequence alignment tools, detection tools for genomic antimicrobial resistance determinants, as well as resistance prediction models. The clinical challenges for mNGS-based antibacterial resistance prediction have also been reviewed and discussed.
ObjectiveTo analyze the clinical characteristics, risk factors, and drug resistance of pathogenic bacteria in patients with blood stream infections (BSI) after orthopedic surgery, so as to provide reference and basis for clinical diagnosis and treatment.MethodsA retrospective analysis was made on the clinical data of 6 348 orthopedic patients admitted for surgery between January 2017 and December 2019. There were 3 598 males and 2 750 females. Their age ranged from 18 to 98 years, with an average of 66 years. The data of patients were collected, and the risk factors of BSI were analyzed by univariate analysis and logistic regression analysis. The distribution of BSI pathogenic bacteria, the results of drug sensitivity test, the incidence of BSI in patients after orthopedic surgery in different years, and the common sites of BSI secondary infection were summarized.ResultsBSI occurred in 106 (1.67%) of 6 348 patients after orthopedic surgery. There were 71 cases (66.98%) of secondary infection. The mortality of postoperative BSI patients was 1.89%, and the difference was significant when compared with that of non-postoperative BSI patients (0.24%) (χ2=5.313, P=0.021). The incidences of BSI in 2017, 2018, and 2019 were 1.18%, 1.53%, and 2.17%, respectively, showing an increasing trend year by year (trend χ2=6.610, P=0.037). Statistical analysis showed that the independent risk factors for BSI after orthopedic surgery (P<0.05) included the trauma, length of hospital stay≥14 days, emergency surgery, postoperative leukocyte counting<4×109/L, level of hemoglobin≤90 g/L, albumin≤30 g/L, the time of indwelling ureter>24 hours, use of deep vein catheter insertion, and merging other site infection. Blood culture showed 56 strains (52.83%) of Gram-positive bacteria, 47 strains (44.34%) of Gram-negative bacteria, and 3 strains (2.83%) of fungi. The top three pathogenic bacteria were coagulase negative Staphylococci (CNS; 36 strains, 33.96%), Escherichia coli (16 strains, 15.09%), and Staphylococcus aureus (15 strains, 14.15%). The detection rates of extended-spectum β-lactamases producing strains of Escherichia coli and Klebsiella pneumoniae were 56.25% (9/16) and 44.44% (4/9), respectively. The detection rates of methicillin-resistant strains in Staphylococcus aureus and CNS were 46.67% (7/15) and 72.22% (26/36), respectively.ConclusionPostoperative BSI in orthopedic patients is caused by multiple factors. Preventive measures should be taken according to related risk factors and perioperative risk assessment should be strengthened. Staphylococcus and Escherichia coli are the most common pathogenic bacteria in BSI after orthopedic surgery. The infection rate and drug-resistant bacteria are increasing year by year. Therefore, drug resistance monitoring should be strengthened.
ObjectiveTo review the research progress on etiology and pathogenesis of spina bifida. MethodsBy consulting relevant domestic and foreign research literature on spina bifida, the classification, epidemic trend, pathogenesis, etiology, prevention and treatment of it were analyzed and summarized. ResultsSpina bifida, a common phenotype of neural tube defects, is classified based on the degree and pattern of malformation associated with neuroectodermal involvement and is due to the disturbance of neural tube closure 28 days before embryonic development. The prevalence of spina bifida varies greatly among different ethnic groups and regions, and its etiology is complex. Currently, some spina bifida patients can be prevented by folic acid supplements, and with the improvement of treatment technology, the short-term and long-term survival rate of children with spina bifida has improved. ConclusionThe research on the pathogenesis of spina bifida will be based on the refined individual information on exposure, genetics, and complex phenotype, and will provide a theoretical basis for improving prevention and treatment strategies through multidisciplinary cooperation.
ObjectiveTo summarize the research progress of osteonecrosis of femoral head (ONFH) following femoral intertrochanteric fractures in adults.MethodsRelevant literature at home and abroad was extensively reviewed to summarize the pathogenesis, high-risk factors, and treatment of ONFH after femoral intertrochanteric fracture in adults.ResultsONFH after femoral intertrochanteric fracture mostly occurs within 2 years after operation, with a lower incidence. At present, it is believed that comminuted and large displacement fractures caused by high-energy injuries, fracture line close to the base of neck, excessive external rotation deformity, improper intramedullary nail entry points, and rough intraoperative manipulating may injury the deep branch of the medial circumflex femoral artery, causing ONFH. Hip replacement is the main treatment for necrosis, which can achieve good results.ConclusionAddressing the above risks, excessive external rotation, overstretching, and rough manipulating should be avoided. Anatomical reduction should be performed during the operation, the nail entry point should be accurate and avoid repeated drilling and thermally bone necrosis.
Epilepsy is one of the common chronic diseases in neurology, and antiepileptic medication is the main treatment method. Studies have shown that epileptic seizures may disrupt the permeability of the blood brain barrier (BBB), and BBB disruption may also lead to epilepsy. This article reviews the mechanism of BBB in the pathogenesis of epilepsy based on relevant research progress, elucidates the relationship between BBB and epilepsy, and proposes possible directions for future research and development of antiepileptic drugs.
Objective To explore clinical effect of failure mode and effect analysis in improving the submission rate of pathogen examination in counterpart supported high-altitude county hospitals, and formulate practical measures and methods suitable for high-altitude county hospitals to improve the submission rate of pathogen examination. Methods Patients admitted to the People’s Hospital of Ganzi County between January and December 2024 were selected. The data of hospitalized patients between January and June 2024 were as the control group, and the data of hospitalized patients between July and December 2024 were as the intervention group. The study analyzed and compared the submission rate of pathogen testing and the pass rate of microbiological test specimens before antimicrobial treatment between the two groups. Results A total of 3 984 patients were included. Among them, there were 1 748 cases in the control group and 2 236 cases in the intervention group. A total of 10 risk factors and 2 high-risk points were identified. There were statistically significant differences in the submission rate of pathogen specimens before antibiotic treatment [36.21% (633/1 748) vs. 49.33% (1 103/2 236); χ2=68.646, P<0.001] and the qualified rate of microbiological test specimens [26.75% (122/456) vs. 36.45% (261/716); χ2=11.910, P=0.001] between the control group and the intervention group. Conclusions Failure mode and effect analysis can effectively find out the weak points in low pathogen examination submission rate in high-altitude county hospitals. According to the high-risk points to guide the formulation of relevant measures, the pathogen submission rate in the region can be effectively improved.
Objective To analyze the characteristics of pathogens causing bloodstream infection (BSI) after cardiovascular surgery, and provide instructions for prevention and treatment of such kind of disease. Methods A retrospective investigation of clinical and pathogenic data of the patients suffering from BSI after cardiovascular surgery in West China Hospital of Sichuan University from January 2015 to December 2016 was performed. There were 61 patients with 36 males and 25 females at average age of 48.2±17.1 years. A percentage of 65.6% (40/61) of the underlying diseases was rheumatic heart disease. Results Sixty-five strains were isolated from the blood culture specimens of the 61 patients. Gram-positive bacteria, gram-negative bacteria and fungi isolates accounted for 56.9% (37/65), 35.4% (23/65), and 7.7% (5/65), respectively. Among these isolates, Streptococcus spp. was predominant (19/65, 29.2%), followed by Staphylococcus epidermidis (8/65, 12.3%), Staphylococcus aureus (6/65, 9.2%), Acinetobacter calcoaceticus- A. baumannii (5/65, 7.7%) and Escherichia coli (5/65, 7.7%). The resistance rate of Streptococcus spp. to erythromycin and clindamycin was 73.4% (14/19) and 63.2% (12/19), while its resistance to cefepime, vancomycin or linezolid was not observed. Staphylococcus spp. showed the resistance rate of 71.4% (10/14) to oxacillin. All of A. calcoaceticus-A. baumannii isolates were multidrug resistant (5/5, 100.0%), and 80.0% (4/5) of them were resistant to imipenem. The isolates producing extended spectrum beta-lactamase accounted for 80.0% (4/5) of E. coli. Conclusion Streptococcus spp. was the common pathogen causing BSI after cardiovascular surgery. Staphylococcus spp. and gram-negative bacilli show high resistance.
Knee osteoarthritis (KOA) is one of the common degenerative joint diseases, which is more common in the middle-aged and elderly population. It shows significant gender differences, with a significantly higher incidence rate in women than in men, seriously affecting the quality of life of patients. However, there are few research reports on the correlation between gender differences and the incidence of KOA both domestically and internationally. Therefore, this article will summarize and analyze the potential causes of gender differences related to the incidence of KOA from five aspects: hormone levels, anatomical biomechanical characteristics, genes, obesity, and exercise-muscle factors. Through a comprehensive review of research progress, the aim is to provide a theoretical basis for gender based personalized treatment of KOA in clinical practice.
Objective To evaluate the basic performance and clinical application value of nanopore sequencing, in order to provide new ideas for the rapid detection of clinical etiology. Methods From December 2021 to May 2022, blood samples from inpatients suspected of bloodstream infection in Renmin Hospital of Wuhan University were collected, and the nanopore sequencing platform and blood culture method were used to simultaneously identify the pathogenic bacteria in the blood samples of the selected patients, and identify the pathogenic bacteria in the blood samples of the selected patients. The basic performance and clinical utility of nanopore sequencing were evaluated. Results A total of 251 patients were included, and 119 patients (47.4%) were found to have pathogens by nanopore sequencing, which was higher than that of 23 patients (9.2%) by blood culture (χ2=79.167, P<0.001). The results of the two methods are not consistent (kappa=0.052, P=0.175). Nanopore sequencing has a certain missed detection rate. In terms of the types of pathogenic bacteria detected, 47 bacteria and 15 fungi were detected by nanopore sequencing. Conclusion Compared with blood culture, nanopore sequencing has a higher detection rate and more types of pathogens. This technology has obvious advantages in the rapid diagnosis of bloodstream infection pathogens.