Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-...Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.展开更多
Precipitation events,which follow a life cycle of initiation,development,and decay,represent the fundamental form of precipitation.Comprehensive and accurate detection of these events is crucial for effective water re...Precipitation events,which follow a life cycle of initiation,development,and decay,represent the fundamental form of precipitation.Comprehensive and accurate detection of these events is crucial for effective water resource management and flood control.However,current investigations on their spatio-temporal patterns remain limited,largely because of the lack of systematic detection indices that are specifically designed for precipitation events,which constrains event-scale research.In this study,we defined a set of precipitation event detection indices(PEDI)that consists of five conventional and fourteen extreme indices to characterize precipitation events from the perspectives of intensity,duration,and frequency.Applications of the PEDI revealed the spatial patterns of hourly precipitation events in China and its first-and second-order river basins from 2008 to 2017.Both conventional and extreme precipitation events displayed spatial distribution patterns that gradually decreased in intensity,duration,and frequency from southeast to northwest China.Compared with those in northwest China,the average values of most PEDIs in southeast China were usually 2-10 times greater for first-order river basins and 3-15 times greater for second-order basins.The PEDI could serve as a reference method for investigating precipitation events at global,regional,and basin scales.展开更多
Processes supported by process-aware information systems are subject to continuous and often subtle changes due to evolving operational,organizational,or regulatory factors.These changes,referred to as incremental con...Processes supported by process-aware information systems are subject to continuous and often subtle changes due to evolving operational,organizational,or regulatory factors.These changes,referred to as incremental concept drift,gradually alter the behavior or structure of processes,making their detection and localization a challenging task.Traditional process mining techniques frequently assume process stationarity and are limited in their ability to detect such drift,particularly from a control-flow perspective.The objective of this research is to develop an interpretable and robust framework capable of detecting and localizing incremental concept drift in event logs,with a specific emphasis on the structural evolution of control-flow semantics in processes.We propose DriftXMiner,a control-flow-aware hybrid framework that combines statistical,machine learning,and process model analysis techniques.The approach comprises three key components:(1)Cumulative Drift Scanner that tracks directional statistical deviations to detect early drift signals;(2)a Temporal Clustering and Drift-Aware Forest Ensemble(DAFE)to capture distributional and classification-level changes in process behavior;and(3)Petri net-based process model reconstruction,which enables the precise localization of structural drift using transition deviation metrics and replay fitness scores.Experimental validation on the BPI Challenge 2017 event log demonstrates that DriftXMiner effectively identifies and localizes gradual and incremental process drift over time.The framework achieves a detection accuracy of 92.5%,a localization precision of 90.3%,and an F1-score of 0.91,outperforming competitive baselines such as CUSUM+Histograms and ADWIN+Alpha Miner.Visual analyses further confirm that identified drift points align with transitions in control-flow models and behavioral cluster structures.DriftXMiner offers a novel and interpretable solution for incremental concept drift detection and localization in dynamic,process-aware systems.By integrating statistical signal accumulation,temporal behavior profiling,and structural process mining,the framework enables finegrained drift explanation and supports adaptive process intelligence in evolving environments.Its modular architecture supports extension to streaming data and real-time monitoring contexts.展开更多
The global monsoon system,encompassing the Asian-Australian,African,and American monsoons,sustains two-thirds of the world’s population by regulating water resources and agriculture.Monsoon anomalies pose severe risk...The global monsoon system,encompassing the Asian-Australian,African,and American monsoons,sustains two-thirds of the world’s population by regulating water resources and agriculture.Monsoon anomalies pose severe risks,including floods and droughts.Recent research associated with the implementation of the Global Monsoons Model Intercomparison Project under the umbrella of CMIP6 has advanced our understanding of its historical variability and driving mechanisms.Observational data reveal a 20th-century shift:increased rainfall pre-1950s,followed by aridification and partial recovery post-1980s,driven by both internal variability(e.g.,Atlantic Multidecadal Oscillation)and external forcings(greenhouse gases,aerosols),while ENSO drives interannual variability through ocean-atmosphere interactions.Future projections under greenhouse forcing suggest long-term monsoon intensification,though regional disparities and model uncertainties persist.Models indicate robust trends but struggle to quantify extremes,where thermodynamic effects(warming-induced moisture rise)uniformly boost heavy rainfall,while dynamical shifts(circulation changes)create spatial heterogeneity.Volcanic eruptions and proposed solar radiation modification(SRM)further complicate predictions:tropical eruptions suppress monsoons,whereas high-latitude events alter cross-equatorial flows,highlighting unresolved feedbacks.The emergent constraint approach is booming in terms of correcting future projections and reducing uncertainty with respect to the global monsoons.Critical challenges remain.Model biases and sparse 20th-century observational data hinder accurate attribution.The interplay between natural variability and anthropogenic forcings,along with nonlinear extreme precipitation risks under warming,demands deeper mechanistic insights.Additionally,SRM’s regional impacts and hemispheric monsoon interactions require systematic evaluation.Addressing these gaps necessitates enhanced observational networks,refined climate models,and interdisciplinary efforts to disentangle multiscale drivers,ultimately improving resilience strategies for monsoon-dependent regions.展开更多
Background:The purpose of this study was to analyze and classify adverse drug events(ADEs)related to ceftazidime/avibactam reported in the Food and Drug Administration Adverse Event Reporting System(FAERS)database and...Background:The purpose of this study was to analyze and classify adverse drug events(ADEs)related to ceftazidime/avibactam reported in the Food and Drug Administration Adverse Event Reporting System(FAERS)database and to evaluate their potential safety signals since the drug’s market introduction.Methods:This analysis systematically extracted and filtered FAERS data for ceftazidime/avibactam from its market launch in 2015 to the last quarter of 2024,utilizing the Medical Dictionary for Regulatory Activities(MedDRA)terminology for ADE recoding.The analysis employed the reporting odds ratio(ROR)method to assess the strength of ADE signals and to identify significant diseases associated with infections,the hepatobiliary system,the urinary system,and the nervous system.Results:A review of 540 adverse reaction reports revealed significant signals of adverse effects related to infections,hepatobiliary disorders,urinary system issues,and neurological impairments,including pathogen resistance,liver and kidney function impairment,encephalopathy,thrombocytopenia,and toxic epidermal necrolysis.However,these issues require further clinical attention.Conclusion:Ceftazidime/avibactam is associated with a range of adverse reactions,necessitating enhanced clinical monitoring,particularly in patients with underlying liver or kidney dysfunction.Continuous risk assessment and vigilant monitoring are critical for its clinical use.However,this study is limited by inherent reporting biases and confounders associated with the spontaneous reporting database(FAERS).Future research should validate these signals through prospective cohort and mechanistic studies and explore personalized risk management strategies for high-risk populations.展开更多
The increased frequency and intensity of heavy rainfall events due to climate change could potentially influence the movement of nutrients from land-based regions into recipient rivers.However,little information is av...The increased frequency and intensity of heavy rainfall events due to climate change could potentially influence the movement of nutrients from land-based regions into recipient rivers.However,little information is available on how the rainfall affect nutrient dynamics in subtropicalmontane rivers with complex land use.This study conducted high-frequency monitoring to study the effects of rainfall on nutrients dynamics in an agricultural river draining to Lake Qiandaohu,a montane reservoir of southeast China.The results showed that riverine total nitrogen(TN)and total phosphorus(TP)concentrations increased continuously with increasing rainfall intensity,while TN:TP decreased.The heavy rainfall and rainstorm drove more than 30%of the annual N and P loading in only 5.20%of the total rainfall period,indicating that increased storm runoff is likely to exacerbate eutrophication in montane reservoirs.NO_(3)^(−)-N is the primary nitrogen form lost,while particulate phosphorus(PP)dominated phosphorus loss.Themain source of N is cropland,and themain source of P is residential area.Spatially,forestedwatersheds have better drainage quality,while it is still a potential source of nonpoint pollution during rainfall events.TN and TP concentrations were significantly higher at sites dominated by cropland and residential area,indicating their substantial contributions to deteriorating river water quality.Temporally,TN and TP concentrations reached high values in May-August when rainfall was most intense,while they were lower in autumn and winter than that in spring and summer under the same rainfall intensities.The results emphasize the influence of rainfall-runoff and land use on dynamics of riverine N and P loads,providing guidance for nutrient load reduction planning for Lake Qiandaohu.展开更多
Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the J...Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the Journal of Sport and Health Science,Liang et al.1 describe results from the UK Biobank data showing the benefits of moderate-to-vigorous intensity physical activity(MVPA)on reducing the risks for vascular events in 11,474 adults with T2D and prediabetes.展开更多
BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHOD...BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHODS This retrospective single-center cohort study included all adult patients undergoing elective evaluation for first cadaveric donor orthotopic LT for liver cirrhosis with or without hepatocellular carcinoma at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricerca e Cura a Carattere Scientifico in Rome,Italy.Cardiac contraindications for LT listing were defined after a center-specific cardiac workup,which included cardiac stress tests for most patients.The diagnostic accuracy of the CAR-OLT score was evaluated using the area under the receiver operating characteristic(AUROC)method.RESULTS A total of 342 LT candidates were evaluated between 2015 and 2019,with a moderate cardiovascular risk profile(37%diabetes,34%hypertension,22%obesity).Of these,80(23%)candidates underwent coronary angiography.Twenty-one(6%)candidates were given cardiac contraindications to LT listing,48%of which were due to coronary artery disease.The CAR-OLT score predicted cardiac contraindications to LT listing with an AUROC of 0.81.The optimal cut-off for sensitivity was a CAR-OLT score≤23,which showed a 99%negative predictive value for cardiac contraindications to LT listing.A total of 84(25%)LT candidates with a CAR-OLT score≤23 underwent 87 non-invasive cardiac tests and 13 coronary angiographies pre-listing,with estimated costs of approximately 48000€.The estimated savings per patient was€574.70 for the Italian National Health System.CONCLUSION A CAR-OLT score≤23 can identify LT candidates who can be safely listed without the need for cardiac stress tests,providing time and cost savings.These findings require external validation.展开更多
Although air pollutant emissions have sharply reduced in recent years,the occurrence of PM_(2.5) pollution events remains an intractable environmental problem in Beijing,and regional transport is the key influence fac...Although air pollutant emissions have sharply reduced in recent years,the occurrence of PM_(2.5) pollution events remains an intractable environmental problem in Beijing,and regional transport is the key influence factor.However,it has been difficult to identify regional transport characteristics and the main contributors to pollution events in recent years.In this study,the relative contribution of regional transport was quantified(61.3%)in PM_(2.5) pollution events during 2018-2021 by the Community Multiscale Air Quality model embedded with the Integrated Source Apportionment Model(CMAQ-ISAM).The four regions with the largest fractional contributions to Beijing for all events were Shandong(7.7%),South Hebei(7.3%),Baoding(6.2%),and Langfang(5.8%).Pollution events were classified into the following types based on regional transport directions:local,southwest(SW),southeast(SE),south-mixed(SM),and others.Based on the transport distance,the SW,SE,and SM types can be subdivided into SW-short,SW-long,SE-short,SE-long,SM-short,SM-long distance from southwest,SM-long distance from southeast,and SM-long distance from southwest and southeast.SE-long was regarded as the most important type,with the highest relative frequency(20%).The transport directions were related to the southwest wind at 925 hPa and southeast wind at 1000 hPa in the south of the Beijing–Tianjin–Hebei(BTH)region,and the distance was mainly controlled by wind strength.The wind-field difference can be attributed to the low-pressure and high-pressure systems that control the BTH region.The results suggest that regional joint pollution control should be optimized based on the transport type.展开更多
On January 7,2025,01:05:15 UTC(9:05 a.m.local time)southern Tibet was rocked by a M_(W)7.1 earthquake(M_(W)=moment magnitude,USGS)centered(28.639°N 87.361°E)in the Lhasa Block north of the India/Eurasia Plat...On January 7,2025,01:05:15 UTC(9:05 a.m.local time)southern Tibet was rocked by a M_(W)7.1 earthquake(M_(W)=moment magnitude,USGS)centered(28.639°N 87.361°E)in the Lhasa Block north of the India/Eurasia Plate boundary,in a remote area about 180 km SW of Xigaze,in Dingri County of Shigatse of the Xizang Autonomous Region(Figure 1).展开更多
BACKGROUND The burden of cannabis use disorder(CUD)in the context of its prevalence and subsequent cardiopulmonary outcomes among cancer patients with severe sepsis is unclear.AIM To address this knowledge gap,especia...BACKGROUND The burden of cannabis use disorder(CUD)in the context of its prevalence and subsequent cardiopulmonary outcomes among cancer patients with severe sepsis is unclear.AIM To address this knowledge gap,especially due to rising patterns of cannabis use and its emerging pharmacological role in cancer.METHODS By applying relevant International Classification of Diseases,Ninth and Tenth Revision,Clinical Modification codes to the National Inpatient Sample database between 2016-2020,we identified CUD(+)and CUD(-)arms among adult cancer admissions with severe sepsis.Comparing the two cohorts,we examined baseline demographic characteristics,epidemiological trends,major adverse cardiac and cerebrovascular events,respiratory failure,hospital cost,and length of stay.We used the Pearsonχ^(2) d test for categorical variables and the Mann-Whitney U test for continuous,non-normally distributed variables.Multivariable regression analysis was used to control for potential confounders.A P value≤0.05 was considered for statistical significance.RESULTS We identified a total of 743520 cancer patients admitted with severe sepsis,of which 4945 had CUD.Demographically,the CUD(+)cohort was more likely to be younger(median age=58 vs 69,P<0.001),male(67.9%vs 57.2%,P<0.001),black(23.7%vs 14.4%,P<0.001),Medicaid enrollees(35.2%vs 10.7%,P<0.001),in whom higher rates of substance use and depression were observed.CUD(+)patients also exhibited a higher prevalence of chronic pulmonary disease but lower rates of cardiovascular comorbidities.There was no significant difference in major adverse cardiac and cerebrovascular events between CUD(+)and CUD(-)cohorts on multivariable regression analysis.However,the CUD(+)cohort had lower all-cause mortality(adjusted odds ratio=0.83,95%confidence interval:0.7-0.97,P<0.001)and respiratory failure(adjusted odds ratio=0.8,95%confidence interval:0.69-0.92,P=0.002).Both groups had similar median length of stay,though CUD(+)patients were more likely to have higher hospital cost compared to CUD(-)patients(median=94574 dollars vs 86615 dollars,P<0.001).CONCLUSION CUD(+)cancer patients with severe sepsis,who tended to be younger,black,males with higher rates of substance use and depression had paradoxically significantly lower odds of all-cause in-hospital mortality and respiratory failure.Future research should aim to better elucidate the underlying mechanisms for these observations.展开更多
The China Seismo-Electromagnetic Satellite(CSES-01)launched on February 2,2018,has been steadily operating in orbit for more than six years,exceeding its designed five-year lifespan expectation.The evaluation results ...The China Seismo-Electromagnetic Satellite(CSES-01)launched on February 2,2018,has been steadily operating in orbit for more than six years,exceeding its designed five-year lifespan expectation.The evaluation results suggest that the satellite platform and the majority of payloads are performing well,and still providing reliable measurements.This report briefly introduces the representative scientific results obtained from CSES-01's fiveyear observations.The first result is the long-term global geophysical field data accumulated for the first time,including the global geomagnetic field,the electromagnetic field and waves in a broad frequency band,the in-situ and profile ionospheric plasma parameters,and the energetic particles.The second result is that a series of data processing and validation methods were obtained,and some of the methods are unique worldwide.The third result is that the geomagnetic field,lithospheric magnetic field,and ionospheric electron density 3D models were built based on CSES-01's data.The fourth result is that statistical features of seismic-ionospheric disturbances were revealed and the direct observational evidence for the electromagnetic wave propagation models in the lithosphere-atmosphere-ionosphere was also confirmed.The fifth result is the physical processing of the space weather events was clearly described,showing CSES-01's good capability of monitoring space weather conditions.展开更多
BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is exp...BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is expected when both diseases co-exist.Therefore,thorough risk stratification is important to inform better clinical practice decisions based on good quality evidence for patient with MAFLD and T2DM.AIM To identify the CVD and cardiovascular event(CVE)risk in a systematic review when MAFLD and T2DM co-exist to inform better clinical practice decisions.METHODS A systematic review was performed by compiling data by searching PubMed,EMBASE and Cochrane Library databases.Quality appraisal of retrieved studies and the meta-analysis were performed using Joanna Briggs Institute(JBI)tool and RevMan 5.4 software respectively.The effect indicators for CVE and CVD risk were expressed as odds ratios(OR)and 95%CI with P-values<0.05 as significant.RESULTS Fourteen(5 cohort and 9 cross-sectional)studies with 370013 participants were included in this review.The metaanalysis of CVE showed that the risk of CVE in T2DM was higher in the MAFLD group when compared to the non-MAFLD group[OR 1.28(95%CI,1.04-1.56)P=0.02]with follow up duration ranging between 5-6 years.The prevalence of CVD in the metanalysis of cross-sectional studies was found to be higher[OR 1.47(95%CI,1.21-1.78)P=0.0001]in T2DM with MAFLD when compared to T2DM without MAFLD.Significant heterogeneity exists due to variations in study design,methodologies,and MAFLD diagnostic criteria,which may have influenced the study's findings.CONCLUSION The presence of MAFLD in T2DM increased the risk of CVE.The prevalence of CVD is higher in T2DM with MAFLD as compared to T2DM without MAFLD.Large well-designed multicentric long-term prospective studies are necessary to appropriately risk stratify the cardiovascular effect of the MAFLD in T2DM patients.展开更多
BACKGROUND Minimally invasive esophagectomy(MIE)is a widely accepted treatment for esophageal cancer,yet it is associated with a significant risk of surgical adverse events(SAEs),which can compromise patient recovery ...BACKGROUND Minimally invasive esophagectomy(MIE)is a widely accepted treatment for esophageal cancer,yet it is associated with a significant risk of surgical adverse events(SAEs),which can compromise patient recovery and long-term survival.Accurate preoperative identification of high-risk patients is critical for improving outcomes.AIM To establish and validate a risk prediction and stratification model for the risk of SAEs in patients with MIE.METHODS This retrospective study included 747 patients who underwent MIE at two centers from January 2019 to February 2024.Patients were separated into a train set(n=549)and a validation set(n=198).After screening by least absolute shrinkage and selection operator regression,multivariate logistic regression analyzed clinical and intraoperative variables to identify independent risk factors for SAEs.A risk stratification model was constructed and validated to predict the probability of SAEs.RESULTS SAEs occurred in 10.2%of patients in train set and 13.6%in the validation set.Patients with SAE had significantly higher complication rate and a longer hospital stay after surgery.The key independent risk factors identified included chronic obstructive pulmonary disease,a history of alcohol consumption,low forced expiratory volume in the first second,and low albumin levels.The stratification model has excellent prediction accuracy,with an area under the curve of 0.889 for the training set and an area under the curve of 0.793 for the validation set.CONCLUSION The developed risk stratification model effectively predicts the risk of SAEs in patients undergoing MIE,facilitating targeted preoperative interventions and improving perioperative management.展开更多
Patients admitted with prediabetes and atrial fibrillation are at high risk for major adverse cardiac or cerebrovascular events independent of confounding variables.The shared pathophysiology between these three serio...Patients admitted with prediabetes and atrial fibrillation are at high risk for major adverse cardiac or cerebrovascular events independent of confounding variables.The shared pathophysiology between these three serious but common diseases and their association with atherosclerotic cardiovascular risk factors establish a vicious circle culminating in high atherogenicity.Because of that,it is of paramount importance to perform risk stratification of patients with prediabetes to define phenotypes that benefit from various interventions.Furthermore,stress hyperglycemia assessment of hospitalized patients and consensus on the definition of prediabetes is vital.The roles lifestyle and metformin play in prediabetes are well established.However,the role of glucagon-like peptide agonists and metabolic surgery is less clear.Prediabetes is considered an intermediate between normoglycemia and diabetes along the blood glucose continuum.One billion people are expected to suffer from prediabetes by the year 2045.Therefore,realworld randomized controlled trials to assess major adverse cardiac or cerebrovascular event risk reduction and reversal/prevention of type 2 diabetes among patients are needed to determine the proper interventions.展开更多
BACKGROUND Since the advent of the 20th century,alongside the progression of medical science and technological advancements,immunotherapy has emerged as a pivotal thera-peutic approach for tumor patients subsequent to...BACKGROUND Since the advent of the 20th century,alongside the progression of medical science and technological advancements,immunotherapy has emerged as a pivotal thera-peutic approach for tumor patients subsequent to undergoing radiotherapy and chemotherapy.Arimab(camrelizumab),a flagship drug in the realm of immuno-therapy,functions as a monoclonal antibody specifically targeting the progra-mmed death protein 1(PD-1).This drug engages with the human PD-1 receptor,effectively inhibiting the PD-1/programmed death ligand 1 signaling pathway.This inhibition results in the restoration of T cell activity and the induction of an anti-tumour response.However,it is noteworthy that such interference could lead to immune-related adverse events resembling autoimmune reactions.The grow-ing availability and clinical use of immune checkpoint inhibitors have raised sig-nificant clinical concerns regarding their safety.Numerous instances of immune-related adverse reactions and the associated management strategies have been extensively reported.Timely identification and diagnosis,coupled with multidi-sciplinary consultation and the prompt administration of immunosuppressants,can effectively address severe immune-related adverse reactions.CASE SUMMARY Arimab(camrelizumab),a monoclonal antibody targeting programmed death protein 1(PD-1),disrupts the PD-1/programmed death ligand 1(PD-L1)inter-action,reactivating T cell function and triggering anti-tumor immunity.However,this disruption may trigger immune-mediated adverse events akin to autoim-mune disorders.Approximately 2.8%of such events manifest as immune-related dermatologic reactions,with 0.7%classified as grade 3,which are infrequently documented.Here,this study describes a case of grade 3 bullous dermatitis occur-ring 15 days after initiating camrelizumab therapy.The patient,a 67-year-old male with oesophageal squamous cell carcinoma,received camrelizumab plus paclitaxel alongside chemotherapy and radiotherapy in early 2022.Due to disease progression,maintenance monotherapy with camrelizumab(200 mg)commenced in June 2022.On the fourth cycle,15 days into treatment,the patient presented with an immune-checkpoint inhibitor-related rash,despite unremarkable test results.Dermatology and pharmacy consultations were conducted,leading to glucocorticoid therapy,topical interventions,and supportive care.Gastric mucosal protection,nutritional supplementation,and other adjunctive treatments were also provided.The patient's symptoms resolved within 15 days post-discharge,resulting in discontinuation of camrelizumab.Like other PD-1 inhibitors,camrelizumab is associated with immune-mediated dermatitis.Thus,optimal management of these events requires a multidisciplinary approach,vigilant monitoring,regular evalua-tions,prompt glucocorticoid administration,and specialized dermatologic care.CONCLUSION The increasing adoption of immune checkpoint inhibitors in clinical practice has prompted substantial concerns about their safety profile.A wide range of immune-related adverse events and corresponding management stra-tegies have been well-documented.Early recognition and accurate diagnosis,combined with interdisciplinary collaboration and swift initiation of immunosuppressive therapy,are essential in managing severe immune-related adverse reactions effectively.This report details the treatment trajectory and outcome of a case involving immune-related cutaneous adverse reactions,providing pertinent clinical insights for future cases.展开更多
文摘Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.
基金National Key Research and Development Program of China,No.2023YFC3206605,No.2021YFC3201102National Natural Science Foundation of China,No.41971035。
文摘Precipitation events,which follow a life cycle of initiation,development,and decay,represent the fundamental form of precipitation.Comprehensive and accurate detection of these events is crucial for effective water resource management and flood control.However,current investigations on their spatio-temporal patterns remain limited,largely because of the lack of systematic detection indices that are specifically designed for precipitation events,which constrains event-scale research.In this study,we defined a set of precipitation event detection indices(PEDI)that consists of five conventional and fourteen extreme indices to characterize precipitation events from the perspectives of intensity,duration,and frequency.Applications of the PEDI revealed the spatial patterns of hourly precipitation events in China and its first-and second-order river basins from 2008 to 2017.Both conventional and extreme precipitation events displayed spatial distribution patterns that gradually decreased in intensity,duration,and frequency from southeast to northwest China.Compared with those in northwest China,the average values of most PEDIs in southeast China were usually 2-10 times greater for first-order river basins and 3-15 times greater for second-order basins.The PEDI could serve as a reference method for investigating precipitation events at global,regional,and basin scales.
文摘Processes supported by process-aware information systems are subject to continuous and often subtle changes due to evolving operational,organizational,or regulatory factors.These changes,referred to as incremental concept drift,gradually alter the behavior or structure of processes,making their detection and localization a challenging task.Traditional process mining techniques frequently assume process stationarity and are limited in their ability to detect such drift,particularly from a control-flow perspective.The objective of this research is to develop an interpretable and robust framework capable of detecting and localizing incremental concept drift in event logs,with a specific emphasis on the structural evolution of control-flow semantics in processes.We propose DriftXMiner,a control-flow-aware hybrid framework that combines statistical,machine learning,and process model analysis techniques.The approach comprises three key components:(1)Cumulative Drift Scanner that tracks directional statistical deviations to detect early drift signals;(2)a Temporal Clustering and Drift-Aware Forest Ensemble(DAFE)to capture distributional and classification-level changes in process behavior;and(3)Petri net-based process model reconstruction,which enables the precise localization of structural drift using transition deviation metrics and replay fitness scores.Experimental validation on the BPI Challenge 2017 event log demonstrates that DriftXMiner effectively identifies and localizes gradual and incremental process drift over time.The framework achieves a detection accuracy of 92.5%,a localization precision of 90.3%,and an F1-score of 0.91,outperforming competitive baselines such as CUSUM+Histograms and ADWIN+Alpha Miner.Visual analyses further confirm that identified drift points align with transitions in control-flow models and behavioral cluster structures.DriftXMiner offers a novel and interpretable solution for incremental concept drift detection and localization in dynamic,process-aware systems.By integrating statistical signal accumulation,temporal behavior profiling,and structural process mining,the framework enables finegrained drift explanation and supports adaptive process intelligence in evolving environments.Its modular architecture supports extension to streaming data and real-time monitoring contexts.
基金supported by the National Key Research and Development Program of China(Grant No.2020YFA0608904)the International Partnership Program of the Chinese Academy of Sciences(Grant Nos.060GJHZ2023079GC and 134111KYSB20160031)+1 种基金supported by the Office of Science,U.S.Department of Energy(DOE)Biological and Environmental Research as part of the Regional and Global Model Analysis program area through the Water Cycle and Climate Extremes Modeling(WACCEM)scientific focus areaoperated for DOE by Battelle Memorial Institute under contract DE-AC05-76RL01830。
文摘The global monsoon system,encompassing the Asian-Australian,African,and American monsoons,sustains two-thirds of the world’s population by regulating water resources and agriculture.Monsoon anomalies pose severe risks,including floods and droughts.Recent research associated with the implementation of the Global Monsoons Model Intercomparison Project under the umbrella of CMIP6 has advanced our understanding of its historical variability and driving mechanisms.Observational data reveal a 20th-century shift:increased rainfall pre-1950s,followed by aridification and partial recovery post-1980s,driven by both internal variability(e.g.,Atlantic Multidecadal Oscillation)and external forcings(greenhouse gases,aerosols),while ENSO drives interannual variability through ocean-atmosphere interactions.Future projections under greenhouse forcing suggest long-term monsoon intensification,though regional disparities and model uncertainties persist.Models indicate robust trends but struggle to quantify extremes,where thermodynamic effects(warming-induced moisture rise)uniformly boost heavy rainfall,while dynamical shifts(circulation changes)create spatial heterogeneity.Volcanic eruptions and proposed solar radiation modification(SRM)further complicate predictions:tropical eruptions suppress monsoons,whereas high-latitude events alter cross-equatorial flows,highlighting unresolved feedbacks.The emergent constraint approach is booming in terms of correcting future projections and reducing uncertainty with respect to the global monsoons.Critical challenges remain.Model biases and sparse 20th-century observational data hinder accurate attribution.The interplay between natural variability and anthropogenic forcings,along with nonlinear extreme precipitation risks under warming,demands deeper mechanistic insights.Additionally,SRM’s regional impacts and hemispheric monsoon interactions require systematic evaluation.Addressing these gaps necessitates enhanced observational networks,refined climate models,and interdisciplinary efforts to disentangle multiscale drivers,ultimately improving resilience strategies for monsoon-dependent regions.
基金Intramural Project of The First Affiliated Hospital of Guangxi University of Chinese Medicine(2018QN008).
文摘Background:The purpose of this study was to analyze and classify adverse drug events(ADEs)related to ceftazidime/avibactam reported in the Food and Drug Administration Adverse Event Reporting System(FAERS)database and to evaluate their potential safety signals since the drug’s market introduction.Methods:This analysis systematically extracted and filtered FAERS data for ceftazidime/avibactam from its market launch in 2015 to the last quarter of 2024,utilizing the Medical Dictionary for Regulatory Activities(MedDRA)terminology for ADE recoding.The analysis employed the reporting odds ratio(ROR)method to assess the strength of ADE signals and to identify significant diseases associated with infections,the hepatobiliary system,the urinary system,and the nervous system.Results:A review of 540 adverse reaction reports revealed significant signals of adverse effects related to infections,hepatobiliary disorders,urinary system issues,and neurological impairments,including pathogen resistance,liver and kidney function impairment,encephalopathy,thrombocytopenia,and toxic epidermal necrolysis.However,these issues require further clinical attention.Conclusion:Ceftazidime/avibactam is associated with a range of adverse reactions,necessitating enhanced clinical monitoring,particularly in patients with underlying liver or kidney dysfunction.Continuous risk assessment and vigilant monitoring are critical for its clinical use.However,this study is limited by inherent reporting biases and confounders associated with the spontaneous reporting database(FAERS).Future research should validate these signals through prospective cohort and mechanistic studies and explore personalized risk management strategies for high-risk populations.
基金supported by the National Natural Science Foundation of China(Nos.U2340209,and 42271126)the NIGLAS Foundation(No.NIGLAS2022GS03)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK20220041)the US National Science Foundation Projects(Nos.1831096,1803697,and 2108917).
文摘The increased frequency and intensity of heavy rainfall events due to climate change could potentially influence the movement of nutrients from land-based regions into recipient rivers.However,little information is available on how the rainfall affect nutrient dynamics in subtropicalmontane rivers with complex land use.This study conducted high-frequency monitoring to study the effects of rainfall on nutrients dynamics in an agricultural river draining to Lake Qiandaohu,a montane reservoir of southeast China.The results showed that riverine total nitrogen(TN)and total phosphorus(TP)concentrations increased continuously with increasing rainfall intensity,while TN:TP decreased.The heavy rainfall and rainstorm drove more than 30%of the annual N and P loading in only 5.20%of the total rainfall period,indicating that increased storm runoff is likely to exacerbate eutrophication in montane reservoirs.NO_(3)^(−)-N is the primary nitrogen form lost,while particulate phosphorus(PP)dominated phosphorus loss.Themain source of N is cropland,and themain source of P is residential area.Spatially,forestedwatersheds have better drainage quality,while it is still a potential source of nonpoint pollution during rainfall events.TN and TP concentrations were significantly higher at sites dominated by cropland and residential area,indicating their substantial contributions to deteriorating river water quality.Temporally,TN and TP concentrations reached high values in May-August when rainfall was most intense,while they were lower in autumn and winter than that in spring and summer under the same rainfall intensities.The results emphasize the influence of rainfall-runoff and land use on dynamics of riverine N and P loads,providing guidance for nutrient load reduction planning for Lake Qiandaohu.
文摘Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the Journal of Sport and Health Science,Liang et al.1 describe results from the UK Biobank data showing the benefits of moderate-to-vigorous intensity physical activity(MVPA)on reducing the risks for vascular events in 11,474 adults with T2D and prediabetes.
文摘BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHODS This retrospective single-center cohort study included all adult patients undergoing elective evaluation for first cadaveric donor orthotopic LT for liver cirrhosis with or without hepatocellular carcinoma at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricerca e Cura a Carattere Scientifico in Rome,Italy.Cardiac contraindications for LT listing were defined after a center-specific cardiac workup,which included cardiac stress tests for most patients.The diagnostic accuracy of the CAR-OLT score was evaluated using the area under the receiver operating characteristic(AUROC)method.RESULTS A total of 342 LT candidates were evaluated between 2015 and 2019,with a moderate cardiovascular risk profile(37%diabetes,34%hypertension,22%obesity).Of these,80(23%)candidates underwent coronary angiography.Twenty-one(6%)candidates were given cardiac contraindications to LT listing,48%of which were due to coronary artery disease.The CAR-OLT score predicted cardiac contraindications to LT listing with an AUROC of 0.81.The optimal cut-off for sensitivity was a CAR-OLT score≤23,which showed a 99%negative predictive value for cardiac contraindications to LT listing.A total of 84(25%)LT candidates with a CAR-OLT score≤23 underwent 87 non-invasive cardiac tests and 13 coronary angiographies pre-listing,with estimated costs of approximately 48000€.The estimated savings per patient was€574.70 for the Italian National Health System.CONCLUSION A CAR-OLT score≤23 can identify LT candidates who can be safely listed without the need for cardiac stress tests,providing time and cost savings.These findings require external validation.
基金supported by the National Key R&D program of China(No.2022YFC3703404)the National Natural Science Foundation of China(No.22188102)the Samsung Advanced Institute of Technology.
文摘Although air pollutant emissions have sharply reduced in recent years,the occurrence of PM_(2.5) pollution events remains an intractable environmental problem in Beijing,and regional transport is the key influence factor.However,it has been difficult to identify regional transport characteristics and the main contributors to pollution events in recent years.In this study,the relative contribution of regional transport was quantified(61.3%)in PM_(2.5) pollution events during 2018-2021 by the Community Multiscale Air Quality model embedded with the Integrated Source Apportionment Model(CMAQ-ISAM).The four regions with the largest fractional contributions to Beijing for all events were Shandong(7.7%),South Hebei(7.3%),Baoding(6.2%),and Langfang(5.8%).Pollution events were classified into the following types based on regional transport directions:local,southwest(SW),southeast(SE),south-mixed(SM),and others.Based on the transport distance,the SW,SE,and SM types can be subdivided into SW-short,SW-long,SE-short,SE-long,SM-short,SM-long distance from southwest,SM-long distance from southeast,and SM-long distance from southwest and southeast.SE-long was regarded as the most important type,with the highest relative frequency(20%).The transport directions were related to the southwest wind at 925 hPa and southeast wind at 1000 hPa in the south of the Beijing–Tianjin–Hebei(BTH)region,and the distance was mainly controlled by wind strength.The wind-field difference can be attributed to the low-pressure and high-pressure systems that control the BTH region.The results suggest that regional joint pollution control should be optimized based on the transport type.
文摘On January 7,2025,01:05:15 UTC(9:05 a.m.local time)southern Tibet was rocked by a M_(W)7.1 earthquake(M_(W)=moment magnitude,USGS)centered(28.639°N 87.361°E)in the Lhasa Block north of the India/Eurasia Plate boundary,in a remote area about 180 km SW of Xigaze,in Dingri County of Shigatse of the Xizang Autonomous Region(Figure 1).
文摘BACKGROUND The burden of cannabis use disorder(CUD)in the context of its prevalence and subsequent cardiopulmonary outcomes among cancer patients with severe sepsis is unclear.AIM To address this knowledge gap,especially due to rising patterns of cannabis use and its emerging pharmacological role in cancer.METHODS By applying relevant International Classification of Diseases,Ninth and Tenth Revision,Clinical Modification codes to the National Inpatient Sample database between 2016-2020,we identified CUD(+)and CUD(-)arms among adult cancer admissions with severe sepsis.Comparing the two cohorts,we examined baseline demographic characteristics,epidemiological trends,major adverse cardiac and cerebrovascular events,respiratory failure,hospital cost,and length of stay.We used the Pearsonχ^(2) d test for categorical variables and the Mann-Whitney U test for continuous,non-normally distributed variables.Multivariable regression analysis was used to control for potential confounders.A P value≤0.05 was considered for statistical significance.RESULTS We identified a total of 743520 cancer patients admitted with severe sepsis,of which 4945 had CUD.Demographically,the CUD(+)cohort was more likely to be younger(median age=58 vs 69,P<0.001),male(67.9%vs 57.2%,P<0.001),black(23.7%vs 14.4%,P<0.001),Medicaid enrollees(35.2%vs 10.7%,P<0.001),in whom higher rates of substance use and depression were observed.CUD(+)patients also exhibited a higher prevalence of chronic pulmonary disease but lower rates of cardiovascular comorbidities.There was no significant difference in major adverse cardiac and cerebrovascular events between CUD(+)and CUD(-)cohorts on multivariable regression analysis.However,the CUD(+)cohort had lower all-cause mortality(adjusted odds ratio=0.83,95%confidence interval:0.7-0.97,P<0.001)and respiratory failure(adjusted odds ratio=0.8,95%confidence interval:0.69-0.92,P=0.002).Both groups had similar median length of stay,though CUD(+)patients were more likely to have higher hospital cost compared to CUD(-)patients(median=94574 dollars vs 86615 dollars,P<0.001).CONCLUSION CUD(+)cancer patients with severe sepsis,who tended to be younger,black,males with higher rates of substance use and depression had paradoxically significantly lower odds of all-cause in-hospital mortality and respiratory failure.Future research should aim to better elucidate the underlying mechanisms for these observations.
基金a project funded by the China National Space Administration(CNSA)China Earthquake Administration(CEA)+3 种基金supported by the National Key Research and Development Program of China 2023YFE0117300the National Natural Science Foundation of China Grant 4187417the APSCO Earthquake Research Project PhaseⅡ,and the Dragon 5 cooperation 2020–2024(ID.59236)the CSES02 project。
文摘The China Seismo-Electromagnetic Satellite(CSES-01)launched on February 2,2018,has been steadily operating in orbit for more than six years,exceeding its designed five-year lifespan expectation.The evaluation results suggest that the satellite platform and the majority of payloads are performing well,and still providing reliable measurements.This report briefly introduces the representative scientific results obtained from CSES-01's fiveyear observations.The first result is the long-term global geophysical field data accumulated for the first time,including the global geomagnetic field,the electromagnetic field and waves in a broad frequency band,the in-situ and profile ionospheric plasma parameters,and the energetic particles.The second result is that a series of data processing and validation methods were obtained,and some of the methods are unique worldwide.The third result is that the geomagnetic field,lithospheric magnetic field,and ionospheric electron density 3D models were built based on CSES-01's data.The fourth result is that statistical features of seismic-ionospheric disturbances were revealed and the direct observational evidence for the electromagnetic wave propagation models in the lithosphere-atmosphere-ionosphere was also confirmed.The fifth result is the physical processing of the space weather events was clearly described,showing CSES-01's good capability of monitoring space weather conditions.
文摘BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)and type 2 diabetes mellitus(T2DM)are independent risk factors for the development of cardiovascular disease(CVD)and an exaggerated CVD risk is expected when both diseases co-exist.Therefore,thorough risk stratification is important to inform better clinical practice decisions based on good quality evidence for patient with MAFLD and T2DM.AIM To identify the CVD and cardiovascular event(CVE)risk in a systematic review when MAFLD and T2DM co-exist to inform better clinical practice decisions.METHODS A systematic review was performed by compiling data by searching PubMed,EMBASE and Cochrane Library databases.Quality appraisal of retrieved studies and the meta-analysis were performed using Joanna Briggs Institute(JBI)tool and RevMan 5.4 software respectively.The effect indicators for CVE and CVD risk were expressed as odds ratios(OR)and 95%CI with P-values<0.05 as significant.RESULTS Fourteen(5 cohort and 9 cross-sectional)studies with 370013 participants were included in this review.The metaanalysis of CVE showed that the risk of CVE in T2DM was higher in the MAFLD group when compared to the non-MAFLD group[OR 1.28(95%CI,1.04-1.56)P=0.02]with follow up duration ranging between 5-6 years.The prevalence of CVD in the metanalysis of cross-sectional studies was found to be higher[OR 1.47(95%CI,1.21-1.78)P=0.0001]in T2DM with MAFLD when compared to T2DM without MAFLD.Significant heterogeneity exists due to variations in study design,methodologies,and MAFLD diagnostic criteria,which may have influenced the study's findings.CONCLUSION The presence of MAFLD in T2DM increased the risk of CVE.The prevalence of CVD is higher in T2DM with MAFLD as compared to T2DM without MAFLD.Large well-designed multicentric long-term prospective studies are necessary to appropriately risk stratify the cardiovascular effect of the MAFLD in T2DM patients.
基金Supported by Joint Funds for the Innovation of Science and Technology,Fujian Province,No.2023Y9187 and No.2021Y9057.
文摘BACKGROUND Minimally invasive esophagectomy(MIE)is a widely accepted treatment for esophageal cancer,yet it is associated with a significant risk of surgical adverse events(SAEs),which can compromise patient recovery and long-term survival.Accurate preoperative identification of high-risk patients is critical for improving outcomes.AIM To establish and validate a risk prediction and stratification model for the risk of SAEs in patients with MIE.METHODS This retrospective study included 747 patients who underwent MIE at two centers from January 2019 to February 2024.Patients were separated into a train set(n=549)and a validation set(n=198).After screening by least absolute shrinkage and selection operator regression,multivariate logistic regression analyzed clinical and intraoperative variables to identify independent risk factors for SAEs.A risk stratification model was constructed and validated to predict the probability of SAEs.RESULTS SAEs occurred in 10.2%of patients in train set and 13.6%in the validation set.Patients with SAE had significantly higher complication rate and a longer hospital stay after surgery.The key independent risk factors identified included chronic obstructive pulmonary disease,a history of alcohol consumption,low forced expiratory volume in the first second,and low albumin levels.The stratification model has excellent prediction accuracy,with an area under the curve of 0.889 for the training set and an area under the curve of 0.793 for the validation set.CONCLUSION The developed risk stratification model effectively predicts the risk of SAEs in patients undergoing MIE,facilitating targeted preoperative interventions and improving perioperative management.
文摘Patients admitted with prediabetes and atrial fibrillation are at high risk for major adverse cardiac or cerebrovascular events independent of confounding variables.The shared pathophysiology between these three serious but common diseases and their association with atherosclerotic cardiovascular risk factors establish a vicious circle culminating in high atherogenicity.Because of that,it is of paramount importance to perform risk stratification of patients with prediabetes to define phenotypes that benefit from various interventions.Furthermore,stress hyperglycemia assessment of hospitalized patients and consensus on the definition of prediabetes is vital.The roles lifestyle and metformin play in prediabetes are well established.However,the role of glucagon-like peptide agonists and metabolic surgery is less clear.Prediabetes is considered an intermediate between normoglycemia and diabetes along the blood glucose continuum.One billion people are expected to suffer from prediabetes by the year 2045.Therefore,realworld randomized controlled trials to assess major adverse cardiac or cerebrovascular event risk reduction and reversal/prevention of type 2 diabetes among patients are needed to determine the proper interventions.
文摘BACKGROUND Since the advent of the 20th century,alongside the progression of medical science and technological advancements,immunotherapy has emerged as a pivotal thera-peutic approach for tumor patients subsequent to undergoing radiotherapy and chemotherapy.Arimab(camrelizumab),a flagship drug in the realm of immuno-therapy,functions as a monoclonal antibody specifically targeting the progra-mmed death protein 1(PD-1).This drug engages with the human PD-1 receptor,effectively inhibiting the PD-1/programmed death ligand 1 signaling pathway.This inhibition results in the restoration of T cell activity and the induction of an anti-tumour response.However,it is noteworthy that such interference could lead to immune-related adverse events resembling autoimmune reactions.The grow-ing availability and clinical use of immune checkpoint inhibitors have raised sig-nificant clinical concerns regarding their safety.Numerous instances of immune-related adverse reactions and the associated management strategies have been extensively reported.Timely identification and diagnosis,coupled with multidi-sciplinary consultation and the prompt administration of immunosuppressants,can effectively address severe immune-related adverse reactions.CASE SUMMARY Arimab(camrelizumab),a monoclonal antibody targeting programmed death protein 1(PD-1),disrupts the PD-1/programmed death ligand 1(PD-L1)inter-action,reactivating T cell function and triggering anti-tumor immunity.However,this disruption may trigger immune-mediated adverse events akin to autoim-mune disorders.Approximately 2.8%of such events manifest as immune-related dermatologic reactions,with 0.7%classified as grade 3,which are infrequently documented.Here,this study describes a case of grade 3 bullous dermatitis occur-ring 15 days after initiating camrelizumab therapy.The patient,a 67-year-old male with oesophageal squamous cell carcinoma,received camrelizumab plus paclitaxel alongside chemotherapy and radiotherapy in early 2022.Due to disease progression,maintenance monotherapy with camrelizumab(200 mg)commenced in June 2022.On the fourth cycle,15 days into treatment,the patient presented with an immune-checkpoint inhibitor-related rash,despite unremarkable test results.Dermatology and pharmacy consultations were conducted,leading to glucocorticoid therapy,topical interventions,and supportive care.Gastric mucosal protection,nutritional supplementation,and other adjunctive treatments were also provided.The patient's symptoms resolved within 15 days post-discharge,resulting in discontinuation of camrelizumab.Like other PD-1 inhibitors,camrelizumab is associated with immune-mediated dermatitis.Thus,optimal management of these events requires a multidisciplinary approach,vigilant monitoring,regular evalua-tions,prompt glucocorticoid administration,and specialized dermatologic care.CONCLUSION The increasing adoption of immune checkpoint inhibitors in clinical practice has prompted substantial concerns about their safety profile.A wide range of immune-related adverse events and corresponding management stra-tegies have been well-documented.Early recognition and accurate diagnosis,combined with interdisciplinary collaboration and swift initiation of immunosuppressive therapy,are essential in managing severe immune-related adverse reactions effectively.This report details the treatment trajectory and outcome of a case involving immune-related cutaneous adverse reactions,providing pertinent clinical insights for future cases.
