Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.

Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.

Objective To assess whether degrees of leukoaraiosis (LA) severity is associated with prognoses of patients with acute anterior circulation large-artery occlusive stroke after mechanical thrombectomy.Methods Clinical data of patients with acute anterior circulation large-artery occlusive stroke who underwent mechanical thrombectomy in our hospital from January 2016 to August 2017 were collected. The subjects were divided into non-to-moderate LA group and severe LA group according to preoperative degrees of LA severity; the baseline data, successful reperfusion rate, and symptomatic intracranial hemorrhage rate within 24 h of surgery, good prognosis rate 90 d after surgery (modified Rankin scale [mRS] scores≤2) and mortality 90 d after surgery were analyzed. According to the prognoses, the patients were divided into good prognosis group and poor prognosis group; univariate regression analysis and multivariate Logistic regression analysis were used to evaluate the relations of degrees of LA severity with prognoses 90 d after surgery.Results In these 146 patients, 100 patients were into the non-to-moderate LA group and 46 patients were into the severe LA group. As compared with patients in the non-to-moderate LA group, patients in the severe LA group had significantly older age (70.50 [59.75, 79.75] yearsvs. 79 [73, 82] years), significantly higher baseline NIHSS scores (20 [16, 25])vs. 22 [18, 28]), significantly higher rate of symptomatic intracranial hemorrhage 24 h after surgery (11.0％ [11/100])vs. 26.1％ [12/46]), statistically higher mortality rate 90 d after surgery (14.0％[14/100]) vs. 14.0％ [14/46]), significantly lower successful reperfusion rate (97.0％ [97/100]vs. 84.8％ [39/46]), and statistically lower good prognosis rate (54.0％ [54/100]vs. 21.7％ [10/46],P<0.05). Among the 146 patients, 64 had good prognosis and 82 had poor prognosis; univariate analysis showed that as compared with than those from the good prognosis group, patients from the poor prognosis group had significantly older age (70.50 [59.75, 79.75] years oldvs. 79 [73, 82] years old) and statistically higher baseline NIHSS scores (20 [16, 25]vs. 22 [18, 28]), and significantly higher proportion of central source embolism by TOAST etiology classification (68.8％ [44/64]vs. 76.8％[63/82]) and proportion of severe LA (15.6％ [10/64]vs. 43.9％ [36/82],P<0.05); multivariate Logistic regression analysis showed that severe LA (OR=3.109, 95％CI: 1.241-7.788,P=0.015), age, baseline NIHSS scores, and TOAST etiology classification were all independent risk factors for poor prognosis 90 d after surgery (P<0.05). ConclusionSevere LA may be associated with poor prognosis of patients with acute anterior circulation large-artery occlusive stroke after mechanical thrombectomy.

Objective To evaluate the efficacy and safety of endovascular thrombectomy for acute ischemic stroke due to basilar artery occlusion,and analyze the correlation between baseline clinical features and prognoses.Methods The clinical data of 27 patients with acute stroke due to basilar artery occlusion,admitted to and underwent emergency endovascular thrombectomy in our hospital from February 2016 to March 2017,were analyzed retrospectively.The re-canalization rate and complications were determined and the clinical outcomes were assessed.The correlation between clinical features and prognoses were analyzed.Results Successful re-canalization was achieved in 24 out of 27 patients (88.9 ％),and the mean time from onset to re-canalization was (418.92±223.96) min.Symptomatic intracerebral hemorrhage (SICH) was observed in 2 patients (7.4 ％) and mortality in the first 3 months was 29.6％ (8/27).At 3-month follow up,14 patients (51.8 ％) showed good prognosis (modified Rankin scale [mRS] scores≤＜2) and 13 had poor prognosis.Baseline NIHSS scores (23[12.5,33.8] vs.35[23,39]) and posterior circulation-Alberta Stroke Program Early CT Scale scores (9 [8,10] vs.7 [4,9]) between patients with good prognosis and poor prognosis were significantly different (Z=-2.043,P=0.041;Z=-2.387,P=0.017).Conclusions Endovascular thrombectomy can contribute to a high re-canalization rate and safety.Baseline clinical severity and collateral circulation compensation are associated with clinical prognosis.

Objective To compare the efficacy and safety of direct thrombectomy and bridging therapy for acute large-vessel occlusion in anterior circulation stroke.Methods A retrospective study was performed on clinical data of 146 patients with anterior circulation large-vessel occlusion stroke who accepted direct thrombectomy in our hospital from March 2016 to July 2017;85 patients were in direct thrombectomy group and 61 patients were in bridging therapy group.The clinical characteristics,procedural complications and clinical outcomes between the two groups were compared.Results There were no significant differences between the two groups in age,gender,baseline National Institutes of Health Stroke Scale (NIHSS) scores,percentages of patients with hypertension,diabetes and atrial fibrillation,baseline blood glucose,platelet count,creatinine level,baseline systolic blood pressure,stroke etiology,occlusion site,and anesthesia methods (P＞0.05).There were no significant differences between the two groups in admission-to-CT time,admission-to-puncture time,puncture-to-re-canalization time,and admission-to-re-canalization time (P＞0.05).The successful reperfusion rate (91.8％ vs.95.1％),incidence of symptomatic intracranial hemorrhage (11.8％ vs.21.3％),favorable outcome rate 90 d after treatment (41.2％ vs.47.5％),and mortality (20.0％ vs.18.0％) were not significantly different between the two groups (P＞0.05).Conclusion The efficacy and safety of direct thrombectomy and bridging therapy are similar for acute large-vessel occlusion in anterior circulation stroke.

Objective To establish and assess the new method of APTT assay based on the combinations of Mg2+and Ca2+for lupus anticoagulants(LA)measurements.Methods This prospective study included 309 trisodium citrate anticoagulated plasma samples from 244 random patients and 65 patients with different autoimmune diseases(AID)to establish and assess the method of LA measurement, respectively.Final concentrations of 0,2.0, 4.0, 8.0,16.0 mmol/L Mg2+were added into 25 mmol/L Ca2+solution, and Actin reagent was used to measured plasma APTT of 94 patients.The applied concentration of Mg2+-Ca2+solution was confirmed through the special and significant alteration of APTT from LA-positive and -negative plasma observed in the presence of Mg 2+(test solution).Based on Actin reagent use,the test solution and 25 mmol/L Ca2+solution were applied to measure APTT of patients and normal individuals, respectively, and the ratio of Mg2+-Ca2+-APTT to Ca2+-APTT(Mg2+-Ca2+-APTT indices)and normalized Mg2+-Ca2+-APTT indices(NAR)were calculated, respectively.Mixed plasma NAR was measured,and CV%was calculated to evaluate the repeatability and stability of Mg 2+-Ca2+-APTT method.APTT of 150 patients was measured with the test solution and Actin reagent to calculate Mg 2+-Ca2+-APTT indices, and normalized LA ratio was determined with dRVVT method.The applicability of Mg2+-Ca2+-APTT assay was assessed through comparisons of the results from the two methods.Finally, NAR and NLR of 65 patients with AID(including 26 SLE patients)were measured with Mg2+-Ca2+-APTT assay and dRVVT method, respectively, and ROC curve was also used to assess the efficacy of the two methods for LA measurements.Results In all LA-negative plasma,APTT increased from 28.1 ±4.5 s to 61.2 ±7.9 s in normal APTT group,47.2 ±8.9 s to 97.5 ±10.3 s in increased APTT group,and 27.6 ± 5.1 s to 61.2 ±7.9 s in ACA-positive group when Mg2+increased from 0 to 8 mmol/L in Mg2+-Ca2+solution(F=34.12, 38.9 and 28.35,P<0.01).Following increased Mg2+concentration, APTT shortened from 0 to 4.0 mmol/L, but simultaneously prolonged from 4.0 to 16.0 mmol/L in LA-positive plasma with prolonged or normal APTT(F=31.55 and 39.51, P<0.01), and APTT was significantly higher in 8.0 mmol/L than that in 4.0 mmol/L(P<0.001).The test concentration of Mg 2+/Ca2+solution was 4.0 mmol/L.The within, inter-day CV% of NAR was 1.39%,2.30%, and 3.44%, respectively. According to the judging criteria of <0.966 and >1.034 of Mg2+/Ca2+indices, there was 141 patients with increased indices and NLR <1.20, and 9 patients with decreased ones and NLR≥1.20 in all 150 patients.The area under ROC curve of NAR and NLR for LA detection was 0.913(95%CI:0.848-0.978) and 0.892(95%CI:0.817-0.966), respectively, and the cut-off value was 0.87 and 1.13, respectively. The sensitivity and specificity of NAR(85% and 77%)was higher than that of NLR(81% and 74%), respectively.The accordant rate of positive,negative,and total results between NAR and NLR was 94.4%, 98.5%,and 98%,respectively.Conclusion The method of APTT assay based on Mg2+combining Ca2+for LA measurements is feasible,and can be used to detect plasma LA of patients.

Objective To establish a rat model of tympanosclerosis(TS) by myringotomy and inoculation of streptococcus pneummoniae, and to observe the morphological change in the tympanic membrane (TM) and middle ear mucous.Methods Forty Sprague-Dawley rats were randomly divided into two groups (n=20/group) and then ten in each group were chosen to serve as the control and the other ten were set up for the TS model.Group A (myringotomy): myringotomy was performed on the bilateral TMs of all rats except the control group.Group B (bacterial inoculation): streptococcus pneumoniae was inoculated into the bilateral middle ear cavity of all rats except the control group.The condition of the TMs and the middle ears in the two groups were respectively examined at 2 weeks after myringotomy and at the five time points (1 week, 2 weeks, 4 weeks, 6 weeks, and 8 weeks) after bacterial inoculation.Then the rats were decapitated and the morphological changes were observed by hematoxylin and eosin staining.Results One rat in group B died two weeks after the inoculation.In the two experimental groups, the calcifications were observed in 70%of the TMs (14/20) in group A and in 33.33%of the TMs (6/18) at 8 weeks in group B.At the same time, the inflammatory infiltration and hyaline degeneration markedly appeared in the tympanic membrane and middle ear mucous membrane.In the two control groups, neither morphological changes nor calcifications occurred.Conclusion The current study indicated that the animal model of TS was successfully accomplished by myringotomy and inoculation of streptococcus pneummoniae, and their morphological changes were basically consistent.However, the method of myringotomy is easier to use and can obtain a higher modeling rate in a relatively short time.

Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; complications ; Stomach Neoplasms ; complications

Objective To investigate the prognostic value of regulatory B cells (Bregs) in patients with acute pancreatitis .Methods Flow cytometry analysis was performed to detected the percentages of CD19+IL-10+and CD19+CD24hiCD27hi Bregs in peripheral blood samples collected from patients with acute pancreatitis (36 cases with mild acute pancreatitis and 15 cases with severe acute pancreatitis ) as well as the surface costimulatory molecules including CD80 and CD86 on CD19+CD24hiCD27hi Bregs.Their correlations with lymphocytes and C-reactive protein ( CRP) were further analyzed .Results The numbers of lympho-cytes, CD19+lymphocytes, CD19+IL-10+and CD19+CD24hi CD27hi Bregs in peripheral blood samples col-lected from patients with severe and mild acute pancreatitis as well as the mean fluorescence intensities ( MFI) of CD80 and CD86 were significantly lower than those from healthy subjects .Compared with patients with mild acute pancreatitis , the numbers of lymphocytes and CD 19+lymphocytes , the absolute numbers of CD19+IL-10+and CD19+CD24hiCD27hi Bregs as well as the mean fluorescence intensities (MFI) of CD80 and CD86 in patients with severe acute pancreatitis were significantly decreased .The percentages of CD19+IL-10+and CD19+CD24hiCD27hi Bregs in patients with mild acute pancreatitis were significantly increased af-ter an initial drop , but in patients with severe acute pancreatitis those values were continuously decreased along with the disease progression .The percentage of CD19+IL-10+Bregs was positively correlated with the percentage of CD19+CD24hiCD27hi Bregs and the absolute number of CD19+lymphocytes, but was negatively correlated with CRP .Conclusion The abnormal number and function of CD 19+IL-10+and CD19+CD24 hi CD27hi Bregs might be one of the important reasons causing immune dysfunction in patients with acute pan -creatitis.

Aged ; Arthritis ; microbiology ; Candida tropicalis ; Candidiasis ; Female ; Humans ; Multiple Myeloma ; microbiology