Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment ...Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment style may have a role in shaping such associations.Aims This study aims to provide a unified model of the impact of ACEs on NSSI,exploring complex post-traumatic stress disorder(cPTSD)symptoms and dissociation as potential mediators and the role of the predominant attachment style in affecting such associations.Methods 1010 young individuals attending the last year of high school participated in this cross-sectional study.ACEs,cPTSD,dissociation and NSSI were evaluated using self-report questionnaires.We fitted a path model of NSSI,with ACEs as exogenous variables and cPTSD and dissociation as sequential mediators.Secure,fearful and preoccupied attachment styles were modelled as grouping variables.Results Our findings showed that dissociation mediated the impact of ACEs on NSSI in subjects with a fearful attachment style,as opposed to those with a preoccupied attachment for whom cPTSD symptoms mediated the ACEs-NSSI association.Conclusions Attachment styles moderate the relationship between ACEs and NSSI,with either dissociation or post-traumatic symptomatology mediating the impact of ACEs on NSSI,depending on the predominant attachment style.Our results highlight the importance of attachment as a pathway modifier in the relationships between different psychopathology dimensions,providing a useful framework to better conceptualise the ACEs-NSSI association.展开更多
AIM: To study the association between self-reported peptic ulcer and childhood adversities.METHODS: The Health and Social Support Study (HeS-Sup) population consisted of a stratif ied random sample drawn from the Finn...AIM: To study the association between self-reported peptic ulcer and childhood adversities.METHODS: The Health and Social Support Study (HeS-Sup) population consisted of a stratif ied random sample drawn from the Finnish Population Register in four age groups: 20-24, 30-34, 40-44 and 50-54. The survey was carried out by postal questionnaire during 1998, with a response rate of 40.0%. A follow-up questionnaire was sent during 2003 to all those who responded to the f irst. Altogether 19 626 individuals returned the follow-up questionnaire; a response rate of 75.8%. The subjects were asked whether a doctor had told them that they have or have had peptic ulcer. The analyses covered those who responded aff irmatively to both the baseline and the follow-up enquiries (n = 718). Those not re-porting a peptic ulcer in either of the two questionnaires (n = 17 677) were taken as controls. The subjects were further requested (through six questions) to think about their childhood adversities.RESULTS: The most common adversities mentioned were long-lasting financial difficulties in the family, serious conflicts in the family, and a family member seriously or chronically ill. All the adversities reported, except parental divorce, were more common among peptic ulcer patients than among controls (P values varied between < 0.001 and 0.003). Age- and sex-adjusted odds ratios (OR) of childhood adversities in the multivariate logistic analysis for self-reported pep-tic ulcer varied between 1.45 and 2.01. Adjusting for smoking, heavy drinking, stress and nonsteroidal anti-inflammatory drug use had no further influence (ORs between 1.22 and 1.73).CONCLUSION: Our findings suggest that childhood adversities maintain a connection with and have a predictive role in the development of peptic ulcer.展开更多
Background: It has been suggested that childhood events increase the risk of suffering from an eating disorder (ED) in adolescence or young adulthood. Our study here aimed at investigating whether there was an associa...Background: It has been suggested that childhood events increase the risk of suffering from an eating disorder (ED) in adolescence or young adulthood. Our study here aimed at investigating whether there was an association between stressful childhood events and eating disorders later in life. Methods: Our population-based study was a part of the HeSSup (The Health and Social Support) postal survey in 2003, a follow-up survey with a random sample of working-aged subjects drawn from the Finnish Population Register in 1998. Participants in this study reported having been suffering from ED (N = 374), while controls (N = 18,639) reported no history of eating disorder in the questionnaire both in 1998 and 2003. The questionnaire included six questions related to childhood adversities. Results: Each childhood stressor increased the risk of developing ED cumulatively (one adversity OR 1.7 versus all six OR 8.3). Intrafamiliar conflicts (OR 2.0), being afraid of a family member (OR 1.5) or long-term illnesses in the family (OR 1.4) increased the ED-risk statistical significantly. Conclusion: Children exposed to stress are more likely to suffer from eating disorders as adults than those not exposed.展开更多
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
Objective:To characterize placental morphologic features in Moroccan women with adverse outcomes,across different clinical contexts,based on the Amsterdam consensus classification.Methods:A prospective analysis was co...Objective:To characterize placental morphologic features in Moroccan women with adverse outcomes,across different clinical contexts,based on the Amsterdam consensus classification.Methods:A prospective analysis was conducted on placentas with umbilical cords collected fresh between March 1,2024 and July 15,2024 from women with adverse pregnancy outcomes.Clinical data(age,parity,gravidity,complications)were retrieved.Macroscopic parameters(weight,dimensions,cord insertion,membranes,lesions)were assessed,followed by systematic sampling.Tissue was processed by standard histology(formalin fixation,paraffin embedding,hematoxylin and eosin staining),and lesions were classified per Amsterdam criteria.Results:16 placentas from patients with adverse pregnancy outcomes were included.The median maternal age was 30 years.Adverse conditions included placental abruption(50%),intrauterine growth restriction(IUGR,38%),intrauterine fetal death(IUFD,31%),pre-eclampsia/eclampsia(19%),premature rupture of membranes(13%),and oligohydramnios(13%).Several placentas were associated with more than one adverse condition.Histopathology revealed maternal vascular malperfusion lesions in 94%,particularly in pre-eclampsia,IUGR,and IUFD.Fetal vascular malperfusion was found in 88%,mainly in IUGR and IUFD.Inflammatory lesions,dominated by acute maternal and fetal responses stage 3(necrotizing chorioamnionitis and funisitis),were primarily linked to IUFD.Conclusions:Placental examination enhances understanding of the pathophysiology underlying adverse pregnancy outcomes,supports diagnostic confirmation,and guides preventive strategies for recurrence.This study highlights the prevalence of maternal vascular malperfusion in Moroccan women and emphasizes the importance of systematic placental histopathology in obstetric care.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
Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-b...Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.展开更多
BACKGROUND Propofol has been widely used in bidirectional gastrointestinal endoscopy sedation;however,it frequently leads to cardiovascular adverse events and respiratory depression.Propofol target-controlled infusion...BACKGROUND Propofol has been widely used in bidirectional gastrointestinal endoscopy sedation;however,it frequently leads to cardiovascular adverse events and respiratory depression.Propofol target-controlled infusion(TCI)can provide safe sedation but may require higher dosages of propofol.On the contrary,etomidate offers hemodynamic stability.AIM To evaluate the effect of different dose etomidate added to propofol TCI sedation during same-visit bidirectional endoscopy.METHODS A total of 330 patients from Fujian Provincial Hospital were randomly divided into three groups:P,0.1EP,and 0.15EP.Patients in the P group received propofol TCI only,with an initial effect-site concentration of the propofol TCI system of 3.0 mg/mL.Patients in the 0.1EP and 0.15EP groups received 0.1 and 0.15 mg/kg etomidate intravenous injection,respectively,followed by propofol TCI.RESULTS Patients in the 0.15EP group had higher mean blood pressure after induction than the other groups(P group:78 mmHg,0.1EP group:82 mmHg,0.15EP group:88 mmHg;P<0.05).Total doses of propofol consumption significantly decreased in the 0.15EP group compared with that in the other groups(P group:260.6 mg,0.1EP group:228.1 mg,0.15EP group:201.2 mg;P<0.05).The induction time was longer in the P group than in the other groups(P group:1.9±0.7 minutes,0.1EP group:1.2±0.4 minutes,0.15EP group:1.1±0.3 minutes;P<0.01).The recovery time was shorter in the 0.15EP group than in the other groups(P group:4.8±2.1 minutes,0.1EP group:4.5±1.6 minutes,0.15EP group:3.9±1.4 minutes;P<0.01).The incidence of hypotension(P group:36.4%,0.1EP group:29.1%,0.15EP group:11.8%;P<0.01)and injection pain was lower in the 0.15EP group than in the other groups(P<0.05).Furthermore,the incidence of respiratory depression was lower in the 0.15EP group than in the P group(P<0.05).Additionally,the satisfaction of the patient,endoscopist,and anesthesiologist was higher in the 0.15EP group than in the other groups(P<0.05).CONCLUSION Our findings suggest that 0.15 mg/kg etomidate plus propofol TCI can significantly reduce propofol consumption,which is followed by fewer cardiovascular adverse events and respiratory depression,along with higher patient,endoscopist,and anesthesiologist satisfaction.展开更多
Geological analysis,despite being a long-term method for identifying adverse geology in tunnels,has significant limitations due to its reliance on empirical analysis.The quantitative aspects of geochemical anomalies a...Geological analysis,despite being a long-term method for identifying adverse geology in tunnels,has significant limitations due to its reliance on empirical analysis.The quantitative aspects of geochemical anomalies associated with adverse geology provide a novel strategy for addressing these limitations.However,statistical methods for identifying geochemical anomalies are insufficient for tunnel engineering.In contrast,data mining techniques such as machine learning have demonstrated greater efficacy when applied to geological data.Herein,a method for identifying adverse geology using machine learning of geochemical anomalies is proposed.The method was identified geochemical anomalies in tunnel that were not identified by statistical methods.We by employing robust factor analysis and self-organizing maps to reduce the dimensionality of geochemical data and extract the anomaly elements combination(AEC).Using the AEC sample data,we trained an isolation forest model to identify the multi-element anomalies,successfully.We analyzed the adverse geological features based the multi-element anomalies.This study,therefore,extends the traditional approach of geological analysis in tunnels and demonstrates that machine learning is an effective tool for intelligent geological analysis.Correspondingly,the research offers new insights regarding the adverse geology and the prevention of hazards during the construction of tunnels and underground engineering projects.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
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
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
BACKGROUND This manuscript describes the first known cases of sick sinus syndrome(SSS)associated with the use of anlotinib in non-small cell lung cancer patients,highlighting the need for increased vigilance and cardi...BACKGROUND This manuscript describes the first known cases of sick sinus syndrome(SSS)associated with the use of anlotinib in non-small cell lung cancer patients,highlighting the need for increased vigilance and cardiac monitoring.CASE SUMMARY Two patients with non-small cell lung cancer developed SSS after 15 months and 5 months of anlotinib treatment,respectively,presenting with syncope and palpit-ations.Electrocardiogram confirmed SSS,and different treatment approaches were taken for each patient.One patient received a dual-chamber permanent pacemaker,while the other discontinued the medication and experienced symptom resolution.CONCLUSION Anlotinib can induce SSS,suggesting that cardiac monitoring is crucial during anlotinib treatment.Individualized management strategies are necessary for affected individuals.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
BACKGROUND The programmed cell death protein 1 inhibitor pembrolizumab has become a key treatment for various cancers,including triple-negative breast cancer.However,it is associated with immune-related adverse events...BACKGROUND The programmed cell death protein 1 inhibitor pembrolizumab has become a key treatment for various cancers,including triple-negative breast cancer.However,it is associated with immune-related adverse events,including rare but serious neurological complications such as Guillain-Barrésyndrome(GBS).GBS is a potentially life-threatening autoimmune disorder characterized by muscle weakness and paralysis.We present a unique case of pembrolizumab-induced GBS to highlight the importance of recognizing this complication and managing it promptly in patients receiving immune checkpoint inhibitors.CASE SUMMARY A 69-year-old woman with a medical history of hypertension,anxiety,depression,and stage IIIB triple-negative breast cancer treated with pembrolizumab,carboplatin,and paclitaxel,presented to the emergency department with a 1-month history of tingling,lower extremity weakness,and shooting pain.Symptoms progressed to global weakness,ascending paralysis,and double vision.Neurological examination revealed significant lower extremity weakness and sensory deficits.Magnetic resonance imaging of the lumbar spine and cerebrospinal fluid analysis confirmed GBS.Initial treatment with intravenous immunoglobulin led to relapse,requiring additional intravenous immunoglobulin and high-dose glucocorticoids.The patient’s condition improved,pembrolizumab therapy was permanently discontinued,and she was discharged to a rehabilitation facility.CONCLUSION Pembrolizumab can induce GBS,necessitating early recognition,prompt diagnosis,and multidisciplinary management to prevent serious complications.展开更多
Objective:Despite established associations between certain medications and urticaria,the risk profiles of most pharmaceutical agents remain poorly characterized.This investigation aimed to identify risk factors for me...Objective:Despite established associations between certain medications and urticaria,the risk profiles of most pharmaceutical agents remain poorly characterized.This investigation aimed to identify risk factors for medication-induced urticaria through comprehensive analysis of the FDA Adverse Event Reporting System(FAERS)database.Methods:We employed reporting odds ratios(ROR)to evaluate drug-urticaria associations using FAERS data spanning from Q12004 to Q32024.Analytical approaches included univariate screening,LASSO regression,and multivariate logistic regression to identify potential risk factors.Multiple comparison adjustments were implemented using the Bonferroni method.Results:The study identified 1807 pharmaceutical agents potentially associated with urticaria development.Univariate analysis categorized these agents into several therapeutic classes:antimicrobials(19/85),biologics(16/85),analgesics(8/85),dermatologicals(3/85),anti-rheumatic agents(4/85),hormonal preparations(3/85),antihypertensives(2/85),neuropsychiatric medications(2/85),uric acid-lowering drugs(2/85),multiple sclerosis therapies(2/85),and miscellaneous agents(17/85).Multivariate analysis identified three significant risk determinants:middle-aged individuals(36-53 years),female gender,and exposure to any of 82 specific medications.Conclusion:These evidence-based findings provide valuable insights for early clinical recognition of drug-induced urticaria and establish a foundation for subsequent mechanistic investigations into medication-related hypersensitivity reactions.展开更多
Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.Ho...Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.However,determining the optimal dosage and route of administration to minimize toxicity while maintaining efficacy remains challenging.Methods:In this study,we investigated the effect of orally administered tacrolimus in rabbits,with an aim to achieve a whole blood target trough level of 3-10 ng/m L,and looked at signs of tissue rejection after the transplantation of a human nerve conduit to repair a severed fibular nerve.An oral dosage range of 0.25-1.5 mg/kg/d was studied for up to 1 year in 63 New Zealand rabbits.Results:We demonstrated the feasibility of long-term grafting in rabbits while maintaining safe immunosuppression,with side effects mainly limited to diarrhea.Customizing the administered dose proved crucial for graft efficacy and low toxicity,which translated into 100%individual survival.We suggest an oral tacrolimus dose of 1.0-1.5 mg/kg depending on individual heterogeneity and recommend to implement a close therapeutic drug monitoring in the rabbits to maintain a whole blood tacrolimus trough level within the range of 5-12 ng/m L,as levels below 5 ng/m L showed signs of inflammation in the graft.Conclusion:The oral administration of tacrolimus enabled efficient immunosuppression of rabbits over a 1-year period without significant side effects or loss of animals.展开更多
Objective:To assess the effectiveness of COVID-19 vaccination in patients with rheumatic diseases undergoing biologic(bDMARDs)or targeted-synthetic disease-modifying anti-rheumatic drugs(tsDMARDs).Methods:This cross-s...Objective:To assess the effectiveness of COVID-19 vaccination in patients with rheumatic diseases undergoing biologic(bDMARDs)or targeted-synthetic disease-modifying anti-rheumatic drugs(tsDMARDs).Methods:This cross-sectional study was conducted at ten rheumatology clinics in Turkey between May 1,2021,and October 30,2022.Patients with rheumatic diseases on bDMARD or tsDMARD therapy who received at least two doses of an mRNA or inactivated SARS-CoV-2 vaccine were included.After vaccination,COVID-19 infection rates,adverse events,and rheumatic disease flares were recorded.Data were collected via face-to-face or telephone interviews.Results:A total of 963 participants were included in the final analysis;44%were male,and the median age was 49 years.The most frequently observed rheumatic diseases were ankylosing spondylitis and rheumatoid arthritis,accounting for 37.2%and 32.6%of cases,respectively.Adalimumab(19.2%)and infliximab(17.8%)were the most commonly used bDMARDs.Of the participants,634(65.9%)received an inactivated vaccine(CoronaVac)and 329(34.1%)an mRNA vaccine(BioNTech).A total of 502(52.1%)patients received a booster dose.Following the first,second,and third vaccine doses,adverse event rates were 19.9%,15.9%,and 26.7%,respectively.Forty-two(4.4%)patients experienced a disease flare within six months after their first vaccination dose.COVID-19 infection occurred in 79 participants(8.2%)after two vaccine doses;most cases were symptomatic but did not require hospitalization.The COVID-19 infection rate was lower in participants who received a booster dose than those who did not(3.4%vs.8.2%,P<0.001).Conclusions:Our study indicates that both mRNA and inactivated SARS-CoV-2 vaccines are effective in preventing severe COVID-19 outcomes,with an acceptable rate of adverse events and disease flares among patients with rheumatic diseases on bDMARD or tsDMARD therapy.展开更多
BACKGROUND Intra-arterial chemotherapy(IAC)has become a first-line standard treatment for retinoblastoma(RB).However,studies describing its adverse events are sparse,especially from the developing world.Our study desc...BACKGROUND Intra-arterial chemotherapy(IAC)has become a first-line standard treatment for retinoblastoma(RB).However,studies describing its adverse events are sparse,especially from the developing world.Our study described the outcomes and adverse events from a single center in South India.AIM To describe the challenges,treatment outcomes,and complications of selective IAC for RB in Indian eyes.METHODS This study was a single center,retrospective study that included 17 patients with RB who underwent IAC using melphalan(5/7.5 mg)and topotecan(1/2 mg)(n=12)or melphalan(5 mg)alone(n=3)or triple therapy that included carboplatin(30 mg)along with these drugs(n=2)between January 2018 and December 2023.In all,17 IAC procedures were performed using selective ophthalmic artery cannulation.Treatment outcomes were evaluated in terms of tumor control,vitreous and subretinal seed control,complications,and globe salvage rates.RESULTS Out of the 17 patients,11 were diagnosed with unilateral RB and 6 were diag-nosed with bilateral RB.The mean age at the time of diagnosis was 19.8 months.The mean interval between the first symptom and presentation was 6.5 months.IAC was employed as the primary(n=9)or secondary(n=8)modality of treatment.Each eye received a mean of 1.5 IAC sessions(median:1 session;range:1-3 sessions).Eyes were classified according to the international classification of RB as group B(n=5),group C(n=1),group D(n=4),and group E(n=7).Following IAC,complete regression of the main tumor was seen in 15 eyes(88%)and partial regression in 2 eyes(12%).Globe salvage was achieved in 15 eyes(88%).Adverse effects included vitreous hemorrhage(n=3),rhegmatogenous retinal de-tachment(n=2),choroidal ischemia(n=1),isolated subretinal hemorrhage(n=2),retinal pigment epithelium degeneration(n=2),forehead pigmentation(n=1),third nerve palsy with complete ptosis(n=1),and 30-degree exotropia(n=1).The mean follow-up period was 28.6 months(median:24 months,range:1–72 months).CONCLUSION IAC is an effective way to control RB and globe preservation.In the Indian context we encountered many cha-llenges highlighting the importance of case selection.Further studies in India are required to thoroughly un-derstand IAC as a treatment for RB.展开更多
基金supported by #NEXTGENERATIONEU(NGEU)and funded by the Ministry of University and Research(MUR),National Recovery and Resilience Plan(NRRP),project MNESYS(PE0000006)-(DN.155311.10.2022)supported by Sapienza Grant 2021(RM12117A60BDF685).
文摘Background Non-suicidal self-injury(NSSI)is a significant health concern among adolescents and young adults,often resulting from adverse childhood experiences(ACEs).Dissociation,post-traumatic symptoms and attachment style may have a role in shaping such associations.Aims This study aims to provide a unified model of the impact of ACEs on NSSI,exploring complex post-traumatic stress disorder(cPTSD)symptoms and dissociation as potential mediators and the role of the predominant attachment style in affecting such associations.Methods 1010 young individuals attending the last year of high school participated in this cross-sectional study.ACEs,cPTSD,dissociation and NSSI were evaluated using self-report questionnaires.We fitted a path model of NSSI,with ACEs as exogenous variables and cPTSD and dissociation as sequential mediators.Secure,fearful and preoccupied attachment styles were modelled as grouping variables.Results Our findings showed that dissociation mediated the impact of ACEs on NSSI in subjects with a fearful attachment style,as opposed to those with a preoccupied attachment for whom cPTSD symptoms mediated the ACEs-NSSI association.Conclusions Attachment styles moderate the relationship between ACEs and NSSI,with either dissociation or post-traumatic symptomatology mediating the impact of ACEs on NSSI,depending on the predominant attachment style.Our results highlight the importance of attachment as a pathway modifier in the relationships between different psychopathology dimensions,providing a useful framework to better conceptualise the ACEs-NSSI association.
文摘AIM: To study the association between self-reported peptic ulcer and childhood adversities.METHODS: The Health and Social Support Study (HeS-Sup) population consisted of a stratif ied random sample drawn from the Finnish Population Register in four age groups: 20-24, 30-34, 40-44 and 50-54. The survey was carried out by postal questionnaire during 1998, with a response rate of 40.0%. A follow-up questionnaire was sent during 2003 to all those who responded to the f irst. Altogether 19 626 individuals returned the follow-up questionnaire; a response rate of 75.8%. The subjects were asked whether a doctor had told them that they have or have had peptic ulcer. The analyses covered those who responded aff irmatively to both the baseline and the follow-up enquiries (n = 718). Those not re-porting a peptic ulcer in either of the two questionnaires (n = 17 677) were taken as controls. The subjects were further requested (through six questions) to think about their childhood adversities.RESULTS: The most common adversities mentioned were long-lasting financial difficulties in the family, serious conflicts in the family, and a family member seriously or chronically ill. All the adversities reported, except parental divorce, were more common among peptic ulcer patients than among controls (P values varied between < 0.001 and 0.003). Age- and sex-adjusted odds ratios (OR) of childhood adversities in the multivariate logistic analysis for self-reported pep-tic ulcer varied between 1.45 and 2.01. Adjusting for smoking, heavy drinking, stress and nonsteroidal anti-inflammatory drug use had no further influence (ORs between 1.22 and 1.73).CONCLUSION: Our findings suggest that childhood adversities maintain a connection with and have a predictive role in the development of peptic ulcer.
基金Centre for General Practice,Pirkanmaa Hospital District has supported the work financially.
文摘Background: It has been suggested that childhood events increase the risk of suffering from an eating disorder (ED) in adolescence or young adulthood. Our study here aimed at investigating whether there was an association between stressful childhood events and eating disorders later in life. Methods: Our population-based study was a part of the HeSSup (The Health and Social Support) postal survey in 2003, a follow-up survey with a random sample of working-aged subjects drawn from the Finnish Population Register in 1998. Participants in this study reported having been suffering from ED (N = 374), while controls (N = 18,639) reported no history of eating disorder in the questionnaire both in 1998 and 2003. The questionnaire included six questions related to childhood adversities. Results: Each childhood stressor increased the risk of developing ED cumulatively (one adversity OR 1.7 versus all six OR 8.3). Intrafamiliar conflicts (OR 2.0), being afraid of a family member (OR 1.5) or long-term illnesses in the family (OR 1.4) increased the ED-risk statistical significantly. Conclusion: Children exposed to stress are more likely to suffer from eating disorders as adults than those not exposed.
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.
文摘Objective:To characterize placental morphologic features in Moroccan women with adverse outcomes,across different clinical contexts,based on the Amsterdam consensus classification.Methods:A prospective analysis was conducted on placentas with umbilical cords collected fresh between March 1,2024 and July 15,2024 from women with adverse pregnancy outcomes.Clinical data(age,parity,gravidity,complications)were retrieved.Macroscopic parameters(weight,dimensions,cord insertion,membranes,lesions)were assessed,followed by systematic sampling.Tissue was processed by standard histology(formalin fixation,paraffin embedding,hematoxylin and eosin staining),and lesions were classified per Amsterdam criteria.Results:16 placentas from patients with adverse pregnancy outcomes were included.The median maternal age was 30 years.Adverse conditions included placental abruption(50%),intrauterine growth restriction(IUGR,38%),intrauterine fetal death(IUFD,31%),pre-eclampsia/eclampsia(19%),premature rupture of membranes(13%),and oligohydramnios(13%).Several placentas were associated with more than one adverse condition.Histopathology revealed maternal vascular malperfusion lesions in 94%,particularly in pre-eclampsia,IUGR,and IUFD.Fetal vascular malperfusion was found in 88%,mainly in IUGR and IUFD.Inflammatory lesions,dominated by acute maternal and fetal responses stage 3(necrotizing chorioamnionitis and funisitis),were primarily linked to IUFD.Conclusions:Placental examination enhances understanding of the pathophysiology underlying adverse pregnancy outcomes,supports diagnostic confirmation,and guides preventive strategies for recurrence.This study highlights the prevalence of maternal vascular malperfusion in Moroccan women and emphasizes the importance of systematic placental histopathology in obstetric care.
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.
文摘Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.
文摘BACKGROUND Propofol has been widely used in bidirectional gastrointestinal endoscopy sedation;however,it frequently leads to cardiovascular adverse events and respiratory depression.Propofol target-controlled infusion(TCI)can provide safe sedation but may require higher dosages of propofol.On the contrary,etomidate offers hemodynamic stability.AIM To evaluate the effect of different dose etomidate added to propofol TCI sedation during same-visit bidirectional endoscopy.METHODS A total of 330 patients from Fujian Provincial Hospital were randomly divided into three groups:P,0.1EP,and 0.15EP.Patients in the P group received propofol TCI only,with an initial effect-site concentration of the propofol TCI system of 3.0 mg/mL.Patients in the 0.1EP and 0.15EP groups received 0.1 and 0.15 mg/kg etomidate intravenous injection,respectively,followed by propofol TCI.RESULTS Patients in the 0.15EP group had higher mean blood pressure after induction than the other groups(P group:78 mmHg,0.1EP group:82 mmHg,0.15EP group:88 mmHg;P<0.05).Total doses of propofol consumption significantly decreased in the 0.15EP group compared with that in the other groups(P group:260.6 mg,0.1EP group:228.1 mg,0.15EP group:201.2 mg;P<0.05).The induction time was longer in the P group than in the other groups(P group:1.9±0.7 minutes,0.1EP group:1.2±0.4 minutes,0.15EP group:1.1±0.3 minutes;P<0.01).The recovery time was shorter in the 0.15EP group than in the other groups(P group:4.8±2.1 minutes,0.1EP group:4.5±1.6 minutes,0.15EP group:3.9±1.4 minutes;P<0.01).The incidence of hypotension(P group:36.4%,0.1EP group:29.1%,0.15EP group:11.8%;P<0.01)and injection pain was lower in the 0.15EP group than in the other groups(P<0.05).Furthermore,the incidence of respiratory depression was lower in the 0.15EP group than in the P group(P<0.05).Additionally,the satisfaction of the patient,endoscopist,and anesthesiologist was higher in the 0.15EP group than in the other groups(P<0.05).CONCLUSION Our findings suggest that 0.15 mg/kg etomidate plus propofol TCI can significantly reduce propofol consumption,which is followed by fewer cardiovascular adverse events and respiratory depression,along with higher patient,endoscopist,and anesthesiologist satisfaction.
基金the support from the National Natural Science Foundation of China(Nos.52279103,52379103)the Natural Science Foundation of Shandong Province(No.ZR2023YQ049)。
文摘Geological analysis,despite being a long-term method for identifying adverse geology in tunnels,has significant limitations due to its reliance on empirical analysis.The quantitative aspects of geochemical anomalies associated with adverse geology provide a novel strategy for addressing these limitations.However,statistical methods for identifying geochemical anomalies are insufficient for tunnel engineering.In contrast,data mining techniques such as machine learning have demonstrated greater efficacy when applied to geological data.Herein,a method for identifying adverse geology using machine learning of geochemical anomalies is proposed.The method was identified geochemical anomalies in tunnel that were not identified by statistical methods.We by employing robust factor analysis and self-organizing maps to reduce the dimensionality of geochemical data and extract the anomaly elements combination(AEC).Using the AEC sample data,we trained an isolation forest model to identify the multi-element anomalies,successfully.We analyzed the adverse geological features based the multi-element anomalies.This study,therefore,extends the traditional approach of geological analysis in tunnels and demonstrates that machine learning is an effective tool for intelligent geological analysis.Correspondingly,the research offers new insights regarding the adverse geology and the prevention of hazards during the construction of tunnels and underground engineering projects.
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.
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BACKGROUND This manuscript describes the first known cases of sick sinus syndrome(SSS)associated with the use of anlotinib in non-small cell lung cancer patients,highlighting the need for increased vigilance and cardiac monitoring.CASE SUMMARY Two patients with non-small cell lung cancer developed SSS after 15 months and 5 months of anlotinib treatment,respectively,presenting with syncope and palpit-ations.Electrocardiogram confirmed SSS,and different treatment approaches were taken for each patient.One patient received a dual-chamber permanent pacemaker,while the other discontinued the medication and experienced symptom resolution.CONCLUSION Anlotinib can induce SSS,suggesting that cardiac monitoring is crucial during anlotinib treatment.Individualized management strategies are necessary for affected individuals.
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.
文摘BACKGROUND The programmed cell death protein 1 inhibitor pembrolizumab has become a key treatment for various cancers,including triple-negative breast cancer.However,it is associated with immune-related adverse events,including rare but serious neurological complications such as Guillain-Barrésyndrome(GBS).GBS is a potentially life-threatening autoimmune disorder characterized by muscle weakness and paralysis.We present a unique case of pembrolizumab-induced GBS to highlight the importance of recognizing this complication and managing it promptly in patients receiving immune checkpoint inhibitors.CASE SUMMARY A 69-year-old woman with a medical history of hypertension,anxiety,depression,and stage IIIB triple-negative breast cancer treated with pembrolizumab,carboplatin,and paclitaxel,presented to the emergency department with a 1-month history of tingling,lower extremity weakness,and shooting pain.Symptoms progressed to global weakness,ascending paralysis,and double vision.Neurological examination revealed significant lower extremity weakness and sensory deficits.Magnetic resonance imaging of the lumbar spine and cerebrospinal fluid analysis confirmed GBS.Initial treatment with intravenous immunoglobulin led to relapse,requiring additional intravenous immunoglobulin and high-dose glucocorticoids.The patient’s condition improved,pembrolizumab therapy was permanently discontinued,and she was discharged to a rehabilitation facility.CONCLUSION Pembrolizumab can induce GBS,necessitating early recognition,prompt diagnosis,and multidisciplinary management to prevent serious complications.
文摘Objective:Despite established associations between certain medications and urticaria,the risk profiles of most pharmaceutical agents remain poorly characterized.This investigation aimed to identify risk factors for medication-induced urticaria through comprehensive analysis of the FDA Adverse Event Reporting System(FAERS)database.Methods:We employed reporting odds ratios(ROR)to evaluate drug-urticaria associations using FAERS data spanning from Q12004 to Q32024.Analytical approaches included univariate screening,LASSO regression,and multivariate logistic regression to identify potential risk factors.Multiple comparison adjustments were implemented using the Bonferroni method.Results:The study identified 1807 pharmaceutical agents potentially associated with urticaria development.Univariate analysis categorized these agents into several therapeutic classes:antimicrobials(19/85),biologics(16/85),analgesics(8/85),dermatologicals(3/85),anti-rheumatic agents(4/85),hormonal preparations(3/85),antihypertensives(2/85),neuropsychiatric medications(2/85),uric acid-lowering drugs(2/85),multiple sclerosis therapies(2/85),and miscellaneous agents(17/85).Multivariate analysis identified three significant risk determinants:middle-aged individuals(36-53 years),female gender,and exposure to any of 82 specific medications.Conclusion:These evidence-based findings provide valuable insights for early clinical recognition of drug-induced urticaria and establish a foundation for subsequent mechanistic investigations into medication-related hypersensitivity reactions.
基金the Canadian Institutes of Health Research(CIHR),Grant/Award Number:PJT-175016the Fonds de recherche du Québec(FRQ)through the research centre grant for the CHU de Québec-UniversitéLaval Research Center,Grant/Award Number:30641+2 种基金the Quebec Cell,Tissue and Gene Therapy Network—ThéCellthe FRQS,the Fondation du CHU de Québec-UniversitéLavalNeuro Québec。
文摘Background:The absence of well-established immunosuppressed rabbit models poses a significant hurdle in xenograft experiments.Tacrolimus has been identified as a highly promising immunosuppressive agent for rabbits.However,determining the optimal dosage and route of administration to minimize toxicity while maintaining efficacy remains challenging.Methods:In this study,we investigated the effect of orally administered tacrolimus in rabbits,with an aim to achieve a whole blood target trough level of 3-10 ng/m L,and looked at signs of tissue rejection after the transplantation of a human nerve conduit to repair a severed fibular nerve.An oral dosage range of 0.25-1.5 mg/kg/d was studied for up to 1 year in 63 New Zealand rabbits.Results:We demonstrated the feasibility of long-term grafting in rabbits while maintaining safe immunosuppression,with side effects mainly limited to diarrhea.Customizing the administered dose proved crucial for graft efficacy and low toxicity,which translated into 100%individual survival.We suggest an oral tacrolimus dose of 1.0-1.5 mg/kg depending on individual heterogeneity and recommend to implement a close therapeutic drug monitoring in the rabbits to maintain a whole blood tacrolimus trough level within the range of 5-12 ng/m L,as levels below 5 ng/m L showed signs of inflammation in the graft.Conclusion:The oral administration of tacrolimus enabled efficient immunosuppression of rabbits over a 1-year period without significant side effects or loss of animals.
文摘Objective:To assess the effectiveness of COVID-19 vaccination in patients with rheumatic diseases undergoing biologic(bDMARDs)or targeted-synthetic disease-modifying anti-rheumatic drugs(tsDMARDs).Methods:This cross-sectional study was conducted at ten rheumatology clinics in Turkey between May 1,2021,and October 30,2022.Patients with rheumatic diseases on bDMARD or tsDMARD therapy who received at least two doses of an mRNA or inactivated SARS-CoV-2 vaccine were included.After vaccination,COVID-19 infection rates,adverse events,and rheumatic disease flares were recorded.Data were collected via face-to-face or telephone interviews.Results:A total of 963 participants were included in the final analysis;44%were male,and the median age was 49 years.The most frequently observed rheumatic diseases were ankylosing spondylitis and rheumatoid arthritis,accounting for 37.2%and 32.6%of cases,respectively.Adalimumab(19.2%)and infliximab(17.8%)were the most commonly used bDMARDs.Of the participants,634(65.9%)received an inactivated vaccine(CoronaVac)and 329(34.1%)an mRNA vaccine(BioNTech).A total of 502(52.1%)patients received a booster dose.Following the first,second,and third vaccine doses,adverse event rates were 19.9%,15.9%,and 26.7%,respectively.Forty-two(4.4%)patients experienced a disease flare within six months after their first vaccination dose.COVID-19 infection occurred in 79 participants(8.2%)after two vaccine doses;most cases were symptomatic but did not require hospitalization.The COVID-19 infection rate was lower in participants who received a booster dose than those who did not(3.4%vs.8.2%,P<0.001).Conclusions:Our study indicates that both mRNA and inactivated SARS-CoV-2 vaccines are effective in preventing severe COVID-19 outcomes,with an acceptable rate of adverse events and disease flares among patients with rheumatic diseases on bDMARD or tsDMARD therapy.
文摘BACKGROUND Intra-arterial chemotherapy(IAC)has become a first-line standard treatment for retinoblastoma(RB).However,studies describing its adverse events are sparse,especially from the developing world.Our study described the outcomes and adverse events from a single center in South India.AIM To describe the challenges,treatment outcomes,and complications of selective IAC for RB in Indian eyes.METHODS This study was a single center,retrospective study that included 17 patients with RB who underwent IAC using melphalan(5/7.5 mg)and topotecan(1/2 mg)(n=12)or melphalan(5 mg)alone(n=3)or triple therapy that included carboplatin(30 mg)along with these drugs(n=2)between January 2018 and December 2023.In all,17 IAC procedures were performed using selective ophthalmic artery cannulation.Treatment outcomes were evaluated in terms of tumor control,vitreous and subretinal seed control,complications,and globe salvage rates.RESULTS Out of the 17 patients,11 were diagnosed with unilateral RB and 6 were diag-nosed with bilateral RB.The mean age at the time of diagnosis was 19.8 months.The mean interval between the first symptom and presentation was 6.5 months.IAC was employed as the primary(n=9)or secondary(n=8)modality of treatment.Each eye received a mean of 1.5 IAC sessions(median:1 session;range:1-3 sessions).Eyes were classified according to the international classification of RB as group B(n=5),group C(n=1),group D(n=4),and group E(n=7).Following IAC,complete regression of the main tumor was seen in 15 eyes(88%)and partial regression in 2 eyes(12%).Globe salvage was achieved in 15 eyes(88%).Adverse effects included vitreous hemorrhage(n=3),rhegmatogenous retinal de-tachment(n=2),choroidal ischemia(n=1),isolated subretinal hemorrhage(n=2),retinal pigment epithelium degeneration(n=2),forehead pigmentation(n=1),third nerve palsy with complete ptosis(n=1),and 30-degree exotropia(n=1).The mean follow-up period was 28.6 months(median:24 months,range:1–72 months).CONCLUSION IAC is an effective way to control RB and globe preservation.In the Indian context we encountered many cha-llenges highlighting the importance of case selection.Further studies in India are required to thoroughly un-derstand IAC as a treatment for RB.
