Background:Atezolizumab,an immune checkpoint inhibitor,is a humanized monoclonal,anti-programmed death ligand 1(PD-L1)antibody used for the treatment of metastatic urothelial carcinoma that has progressed after chemo-...Background:Atezolizumab,an immune checkpoint inhibitor,is a humanized monoclonal,anti-programmed death ligand 1(PD-L1)antibody used for the treatment of metastatic urothelial carcinoma that has progressed after chemo-therapy.Case Presentation:We describe a patient with a known history of urothelial carcinoma who presented with dia-betic ketoacidosis 6 weeks following his second cycle of atezolizumab.His serum lactate level was slightly elevated(2 mM)and hisβ-hydroxybutyrate level was elevated(3.9 mM).High anion gap metabolic acidosis secondary to dia-betic ketoacidosis was diagnosed.Subsequent testing demonstrated hemoglobin A 1c level of 9.9%,positivity for anti-glutamic acid decarboxylase antibody(0.03 nM,reference range<0.02 nM),and suppressed C-peptide level(0.1μg/L,reference range 0.9-7.1μg/L)in the absence of detectable anti-islet antigen 2(IA-2)or anti-insulin antibodies.His initial management included cessation of atezolizumab treatment,intravenous sodium chloride administration,and insulin pump infusion,after which metabolic acidosis gradually resolved.The insulin pump was subsequently switched to Protaphane at 18 units before breakfast and 8 units before dinner,together with metformin at 1000 mg twice daily.Four weeks later his medication was changed to human isophane insulin plus neutral insulin(70%/30%;Mixtard 30 HM;26 units/4 units).Linagliptin at 5 mg was added 1 month later.His hemoglobin A 1c level declined to 8.1%1 year later.Conclusions:PD-L1 inhibitors can induce type 1 diabetes,and patients can present with diabetic ketoacidosis.Blood glucose levels should be regularly monitored in patients who are prescribed these medications.展开更多
The 12-lead electrocardiogram(ECG)is a routinely performed test but is susceptible to misinterpretation even by experienced physicians.We report a case of a 72-year-old lady with no prior cardiac history presented to ...The 12-lead electrocardiogram(ECG)is a routinely performed test but is susceptible to misinterpretation even by experienced physicians.We report a case of a 72-year-old lady with no prior cardiac history presented to our hospital with atypical chest pain.Her initial electrocardiogram shows an initial ST depression followed by positive defl ections leads I and aVL.Non-physiological ST segment and T-wave changes are also observed in the precordial leads V2 to V6.By contrast,these abnormalities are notably absent in lead II.A repeat of the ECG taken 30 minutes later reveals the resolution of most abnormalities seen in the initial ECG on a background of high-frequency noise in the limb leads.She was referred to the cardiology department for further management.An urgent echocardiogram revealed no regional wall motion abnormalities with preserved ejection fraction,and her coronary angiogram revealed no signifi cant coro-nary stenosis.This case illustrates the importance of understanding different factors that can cause ST segment abnor-malities,notably artifactual changes that can mimic ST segment myocardial infarction.展开更多
OBJECTIVES To assess the effect of vasopressin,steroid and epinephrine(VSE)combination therapy on return of spontan-eous circulation(ROSC)after in-hospital cardiac arrest(IHCA),and test the conclusiveness of evidence ...OBJECTIVES To assess the effect of vasopressin,steroid and epinephrine(VSE)combination therapy on return of spontan-eous circulation(ROSC)after in-hospital cardiac arrest(IHCA),and test the conclusiveness of evidence using trial sequential ana-lysis(TSA).METHODS The systematic search included PubMed,EMBASE,Scopus,and Cochrane Central Register of Controlled Trials.Randomized controlled trials(RCTs)that included adult patients with IHCA,with at least one group receiving combined VSE therapy were selected.Data was extracted independently by two reviewers.The main outcome of interest was ROSC.Other out-comes included survival to hospital discharge or survival to 30 and 90 days,with good neurological outcomes.RESULTS We included a total of three RCTs(n=869).Results showed that VSE combination therapy increased ROSC(risk ra-tio=1.41;95%CI:1.25-1.59)as compared to placebo.TSA demonstrated that the existing evidence is conclusive.This was also validated by the alpha-spending adjusted relative risk(1.32[1.16,1.49],P<0.0001).Other outcomes could not be meta-analysed due to differences in timeframe in the included studies.CONCLUSIONS VSE combination therapy administered in cardiopulmonary resuscitation led to improved rates of ROSC.Fu-ture trials of VSE therapy should evaluate survival to hospital discharge,neurological function and long-term survival.展开更多
BACKGROUND Postoperative atrial fibrillation(POAF)is a common yet understudied clinical issue after coronary artery bypass graft(CABG)leading to higher mortality rates and stroke.This systematic review and metaanalysi...BACKGROUND Postoperative atrial fibrillation(POAF)is a common yet understudied clinical issue after coronary artery bypass graft(CABG)leading to higher mortality rates and stroke.This systematic review and metaanalysis evaluated the rates of adverse outcomes between patients with and without POAF in patients treated with CABG or combined procedures.METHODS The search period was from the beginning of PubMed and Embase to May 18th,2020 with no language restrictions.The inclusion criteria were:(1)studies comparing new onset atrial fibrillation before or after revascularization vs.no new onset AF before or after revascularization.The outcomes assessed included allcause mortality,cardiac death,cerebral vascular accident(CVA),myocardial infarction(MI),repeated revascularization,major adverse cardiac event(MACE),and major adverse cardiac and cerebrovascular events(MACCEs).RESULTS Of the 7,279 entries screened,11 studies comprising of 57,384 patients were included.Compared to nonPOAF,POAF was significantly associated with higher risk of allcause mortality(Risk Ratio(RR)=1.58;95%Confidence Interval(CI):1.42−1.76,P<0.00001)with accompanying high level of heterogeneity(I^(2)=62%).Conclusions Patients with POAF after CABG or combined procedures are at an increased risk of allcause mortality or CVAs.Therefore,POAF after such procedures should be closely monitored and treated judiciously to minimize risk of further complications.While there are studies on POAF versus no POAF on outcomes,the heterogeneity suggests that further studies are needed.展开更多
BACKGROUND Cardiac magnetic resonance(CMR)is a unique tool for non-invasive tissue characterization,especially for identifying fibrosis.AIM To present the existing data regarding the association of electrocardiographi...BACKGROUND Cardiac magnetic resonance(CMR)is a unique tool for non-invasive tissue characterization,especially for identifying fibrosis.AIM To present the existing data regarding the association of electrocardiographic(ECG)markers with myocardial fibrosis identified by CMR-late gadolinium enhancement(LGE).METHODS A systematic search was performed for identifying the relevant studies in Medline and Cochrane databases through February 2021.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com).RESULTS A total of 32 studies were included.In hypertrophic cardiomyopathy(HCM),fragmented QRS(fQRS)is related to the presence and extent of myocardial fibrosis.fQRS and abnormal Q waves are associated with LGE in ischemic cardiomyopathy patients,while fQRS has also been related to fibrosis in myocarditis.Selvester score,abnormal Q waves,and notched QRS have also been associated with LGE.Repolarization abnormalities as reflected by increased Tp-Te,negative Twaves,and higher QT dispersion are related to myocardial fibrosis in HCM patients.In patients with Duchenne muscular dystrophy,a significant correlation between fQRS and the amount of myocardial fibrosis as assessed by LGE-CMR was observed.In atrial fibrillation patients,advanced inter-atrial block is defined as P-wave duration≥120 ms,and biphasic morphology in inferior leads is related to left atrial fibrosis.CONCLUSION Myocardial fibrosis,a reliable marker of prognosis in a broad spectrum of cardiovascular diseases,can be easily understood with an easily applicable ECG.However,more data is needed on a specific disease basis to study the association of ECG markers and myocardial fibrosis as depicted by CMR.展开更多
Background:Routinely collected health data are increasingly used in clinical research.No study has systematically reviewed the temporal trends in the number of publications and analyzed different aspects of local rese...Background:Routinely collected health data are increasingly used in clinical research.No study has systematically reviewed the temporal trends in the number of publications and analyzed different aspects of local research practices and their variations in Hong Kong,China,with a specific focus on research ethics governance and approval.Methods:PubMed was systematically searched from its inception to March 28,2023,for studies using routinely col-lected healthcare data from Hong Kong.Results:A total of 454 studies were included.Between 2000 and 2009,32 studies were identified.The number of pub-lications increased from 5 to 120 between 2010 and 2022.Of the investigator-led studies using the Hospital Authority(HA)’s cross-cluster data(n=393),327(83.2%)reported receiving ethics approval from a single cluster/university-based REC,whereas 50 studies(12.7%)did not report approval from a REC.For use of the HA Data Collaboration Lab,approval by a single hospital-based or University-based REC is accepted.Repeated submission of identical ethics applications to different RECs is estimated to cost HK$4.2 million yearly.Conclusions:Most studies reported gaining approval from a single cluster REC before retrieval of cross-cluster HA data.Substantial cost savings would result if repeated review of identical ethics applications were not required.展开更多
Background:Aromatase inhibitors(AIs)are associated with improved cancer-related survival in breast cancer,but also higher risks of adverse cardiovascular outcomes.This study compared cardiovascular outcomes between so...Background:Aromatase inhibitors(AIs)are associated with improved cancer-related survival in breast cancer,but also higher risks of adverse cardiovascular outcomes.This study compared cardiovascular outcomes between sodium-glucose cotransporter-2 inhibitor(SGLT2i)and dipeptidyl peptidase-4 inhibitor(DPP4i)among breast cancer patients receiving AIs.Methods:This was a retrospective,territory-wide study enrolling female patients≥45 years old with diabetes mellitus and breast cancer who received SGLT2i or DPP4i on the date of AIs initiation,between 2015 and 2020 in Hong Kong.The primary outcome was major adverse cardiovascular events(MACE).The secondary outcomes included components of MACE[stroke/transient ischemic attack(TIA),nonfatal myocardial infarction(MI),and cardiovascular death],heart failure,and all-cause mortality.Multivariable Cox regression was applied to evaluate the association between SGLT2i versus DPP4i with outcomes.Results:Initially,a total of 76147 diabetes patients treated with SGLT2i or DPP4i were identified.After matching,226 patients(mean age,65.5±7.6 years)were included(113 SGLT2i users versus 113 DPP4i users).During a median follow-up of 5.51 years,43(19.02%)patients developed composite MACE.Compared with DPP4i users,SGLT2i was not significantly associated with MACE[hazard ratio(HR):0.54;95%confidence interval(CI):0.27-1.10]in the adjusted model.For the secondary outcomes,breast cancer patients treated with SGLT2i presented with an 84%lower risk of stroke/TIA(HR:0.16;95%CI:0.04-0.61)than DPP4i users after adjustments.No significant associations were observed between SGLT2i with MI(HR:0.41;95%CI:0.10-1.69),cardiovascular mortality(HR:0.86;95%CI:0.20-3.70),all-cause mortality(0.51;95%CI:0.17-1.58),and heart failure(0.47;95%CI:0.12-1.89),in relation to DPP4i.Conclusion:SGLT2i was associated with lower risks of stroke/TIA in diabetic patients with breast cancer receiving AIs compared with DPP4i.展开更多
Background:The role of surgery in metastatic breast cancer(MBC)is currently controversial.Several novel statistical and deep learning(DL)methods promise to infer the suitability of surgery at the individual level.Obje...Background:The role of surgery in metastatic breast cancer(MBC)is currently controversial.Several novel statistical and deep learning(DL)methods promise to infer the suitability of surgery at the individual level.Objective:The objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery required.Methods:We introduced the deep survival regression with mixture effects(DSME),a semi-parametric DL model integrating three causal inference methods.Six models were trained to make individualized treatment recommendations.Patients who received treatments in line with the DL models'recommendations were compared with those who underwent treatments divergent from the recommendations.Inverse probability weighting(IPW)was used to minimize bias.The effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal inference.Results:In total,5269 female patients with MBC were included.DSME was an independent protective factor,outperforming other models in recommend-ing surgery(IPW-adjusted hazard ratio[HR]=0.39,95%confidence interval[CI]:0.19–0.78)and type of surgery(IPW-adjusted HR=0.66,95%CI:0.48–0.93).DSME was superior to other models and traditional guidelines,suggesting a higher proportion of patients benefiting from surgery,especially breast-conserving surgery.The debiased effect of patient characteristics,including age,tumor size,metastatic sites,lymph node status,and breast cancer subtypes,on surgery decision was also quantified.Conclusions:Our findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery needed.This method can facilitate the development of efficient,reliable treatment recommendation systems and provide quantifiable evidence for decision-making.展开更多
Background Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies.However,its use is associated with dose-dependent cardiotoxicity,causing irreversible myocardial damage and sign...Background Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies.However,its use is associated with dose-dependent cardiotoxicity,causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival.In this study,an animal model of doxorubicin-induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin-induced myocardial injury.This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro.Methods Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group.Body weight,echocardiography,surface electrocardiogram,and myocardial histomorphology were measured.The mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups(phosphate-buffered saline,doxorubicin,and doxorubicin with resveratrol).Results Compared to the control group,the doxorubicin group showed a lower body weight and higher systolic arterial pressure,associated with reduced left ventricular ejection fraction and left ventricular fractional shortening,prolonged PR interval,and QT interval.These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes,increased protein expression levels ofα-smooth muscle actin and caspase 3,and reduced protein expression levels of Mitofusin2(MFN2)and Sirtuin1(SIRT1).Compared to the doxorubicin group,doxorubicin+resveratrol treatment reduced caspase 3 and manganese superoxide dismutase,and increased MFN2 and SIRT1 expression levels.Conclusion Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion.Resveratrol ameliorates doxorubicin-induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function.展开更多
文摘Background:Atezolizumab,an immune checkpoint inhibitor,is a humanized monoclonal,anti-programmed death ligand 1(PD-L1)antibody used for the treatment of metastatic urothelial carcinoma that has progressed after chemo-therapy.Case Presentation:We describe a patient with a known history of urothelial carcinoma who presented with dia-betic ketoacidosis 6 weeks following his second cycle of atezolizumab.His serum lactate level was slightly elevated(2 mM)and hisβ-hydroxybutyrate level was elevated(3.9 mM).High anion gap metabolic acidosis secondary to dia-betic ketoacidosis was diagnosed.Subsequent testing demonstrated hemoglobin A 1c level of 9.9%,positivity for anti-glutamic acid decarboxylase antibody(0.03 nM,reference range<0.02 nM),and suppressed C-peptide level(0.1μg/L,reference range 0.9-7.1μg/L)in the absence of detectable anti-islet antigen 2(IA-2)or anti-insulin antibodies.His initial management included cessation of atezolizumab treatment,intravenous sodium chloride administration,and insulin pump infusion,after which metabolic acidosis gradually resolved.The insulin pump was subsequently switched to Protaphane at 18 units before breakfast and 8 units before dinner,together with metformin at 1000 mg twice daily.Four weeks later his medication was changed to human isophane insulin plus neutral insulin(70%/30%;Mixtard 30 HM;26 units/4 units).Linagliptin at 5 mg was added 1 month later.His hemoglobin A 1c level declined to 8.1%1 year later.Conclusions:PD-L1 inhibitors can induce type 1 diabetes,and patients can present with diabetic ketoacidosis.Blood glucose levels should be regularly monitored in patients who are prescribed these medications.
文摘The 12-lead electrocardiogram(ECG)is a routinely performed test but is susceptible to misinterpretation even by experienced physicians.We report a case of a 72-year-old lady with no prior cardiac history presented to our hospital with atypical chest pain.Her initial electrocardiogram shows an initial ST depression followed by positive defl ections leads I and aVL.Non-physiological ST segment and T-wave changes are also observed in the precordial leads V2 to V6.By contrast,these abnormalities are notably absent in lead II.A repeat of the ECG taken 30 minutes later reveals the resolution of most abnormalities seen in the initial ECG on a background of high-frequency noise in the limb leads.She was referred to the cardiology department for further management.An urgent echocardiogram revealed no regional wall motion abnormalities with preserved ejection fraction,and her coronary angiogram revealed no signifi cant coro-nary stenosis.This case illustrates the importance of understanding different factors that can cause ST segment abnor-malities,notably artifactual changes that can mimic ST segment myocardial infarction.
文摘OBJECTIVES To assess the effect of vasopressin,steroid and epinephrine(VSE)combination therapy on return of spontan-eous circulation(ROSC)after in-hospital cardiac arrest(IHCA),and test the conclusiveness of evidence using trial sequential ana-lysis(TSA).METHODS The systematic search included PubMed,EMBASE,Scopus,and Cochrane Central Register of Controlled Trials.Randomized controlled trials(RCTs)that included adult patients with IHCA,with at least one group receiving combined VSE therapy were selected.Data was extracted independently by two reviewers.The main outcome of interest was ROSC.Other out-comes included survival to hospital discharge or survival to 30 and 90 days,with good neurological outcomes.RESULTS We included a total of three RCTs(n=869).Results showed that VSE combination therapy increased ROSC(risk ra-tio=1.41;95%CI:1.25-1.59)as compared to placebo.TSA demonstrated that the existing evidence is conclusive.This was also validated by the alpha-spending adjusted relative risk(1.32[1.16,1.49],P<0.0001).Other outcomes could not be meta-analysed due to differences in timeframe in the included studies.CONCLUSIONS VSE combination therapy administered in cardiopulmonary resuscitation led to improved rates of ROSC.Fu-ture trials of VSE therapy should evaluate survival to hospital discharge,neurological function and long-term survival.
文摘BACKGROUND Postoperative atrial fibrillation(POAF)is a common yet understudied clinical issue after coronary artery bypass graft(CABG)leading to higher mortality rates and stroke.This systematic review and metaanalysis evaluated the rates of adverse outcomes between patients with and without POAF in patients treated with CABG or combined procedures.METHODS The search period was from the beginning of PubMed and Embase to May 18th,2020 with no language restrictions.The inclusion criteria were:(1)studies comparing new onset atrial fibrillation before or after revascularization vs.no new onset AF before or after revascularization.The outcomes assessed included allcause mortality,cardiac death,cerebral vascular accident(CVA),myocardial infarction(MI),repeated revascularization,major adverse cardiac event(MACE),and major adverse cardiac and cerebrovascular events(MACCEs).RESULTS Of the 7,279 entries screened,11 studies comprising of 57,384 patients were included.Compared to nonPOAF,POAF was significantly associated with higher risk of allcause mortality(Risk Ratio(RR)=1.58;95%Confidence Interval(CI):1.42−1.76,P<0.00001)with accompanying high level of heterogeneity(I^(2)=62%).Conclusions Patients with POAF after CABG or combined procedures are at an increased risk of allcause mortality or CVAs.Therefore,POAF after such procedures should be closely monitored and treated judiciously to minimize risk of further complications.While there are studies on POAF versus no POAF on outcomes,the heterogeneity suggests that further studies are needed.
文摘BACKGROUND Cardiac magnetic resonance(CMR)is a unique tool for non-invasive tissue characterization,especially for identifying fibrosis.AIM To present the existing data regarding the association of electrocardiographic(ECG)markers with myocardial fibrosis identified by CMR-late gadolinium enhancement(LGE).METHODS A systematic search was performed for identifying the relevant studies in Medline and Cochrane databases through February 2021.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com).RESULTS A total of 32 studies were included.In hypertrophic cardiomyopathy(HCM),fragmented QRS(fQRS)is related to the presence and extent of myocardial fibrosis.fQRS and abnormal Q waves are associated with LGE in ischemic cardiomyopathy patients,while fQRS has also been related to fibrosis in myocarditis.Selvester score,abnormal Q waves,and notched QRS have also been associated with LGE.Repolarization abnormalities as reflected by increased Tp-Te,negative Twaves,and higher QT dispersion are related to myocardial fibrosis in HCM patients.In patients with Duchenne muscular dystrophy,a significant correlation between fQRS and the amount of myocardial fibrosis as assessed by LGE-CMR was observed.In atrial fibrillation patients,advanced inter-atrial block is defined as P-wave duration≥120 ms,and biphasic morphology in inferior leads is related to left atrial fibrosis.CONCLUSION Myocardial fibrosis,a reliable marker of prognosis in a broad spectrum of cardiovascular diseases,can be easily understood with an easily applicable ECG.However,more data is needed on a specific disease basis to study the association of ECG markers and myocardial fibrosis as depicted by CMR.
文摘Background:Routinely collected health data are increasingly used in clinical research.No study has systematically reviewed the temporal trends in the number of publications and analyzed different aspects of local research practices and their variations in Hong Kong,China,with a specific focus on research ethics governance and approval.Methods:PubMed was systematically searched from its inception to March 28,2023,for studies using routinely col-lected healthcare data from Hong Kong.Results:A total of 454 studies were included.Between 2000 and 2009,32 studies were identified.The number of pub-lications increased from 5 to 120 between 2010 and 2022.Of the investigator-led studies using the Hospital Authority(HA)’s cross-cluster data(n=393),327(83.2%)reported receiving ethics approval from a single cluster/university-based REC,whereas 50 studies(12.7%)did not report approval from a REC.For use of the HA Data Collaboration Lab,approval by a single hospital-based or University-based REC is accepted.Repeated submission of identical ethics applications to different RECs is estimated to cost HK$4.2 million yearly.Conclusions:Most studies reported gaining approval from a single cluster REC before retrieval of cross-cluster HA data.Substantial cost savings would result if repeated review of identical ethics applications were not required.
基金supported by grants from the National Natural Science Foundation of China(82370332,82570390)the Tianjin Key Medical Discipline Construction Project(TJYXZDXK-3-006B)
文摘Background:Aromatase inhibitors(AIs)are associated with improved cancer-related survival in breast cancer,but also higher risks of adverse cardiovascular outcomes.This study compared cardiovascular outcomes between sodium-glucose cotransporter-2 inhibitor(SGLT2i)and dipeptidyl peptidase-4 inhibitor(DPP4i)among breast cancer patients receiving AIs.Methods:This was a retrospective,territory-wide study enrolling female patients≥45 years old with diabetes mellitus and breast cancer who received SGLT2i or DPP4i on the date of AIs initiation,between 2015 and 2020 in Hong Kong.The primary outcome was major adverse cardiovascular events(MACE).The secondary outcomes included components of MACE[stroke/transient ischemic attack(TIA),nonfatal myocardial infarction(MI),and cardiovascular death],heart failure,and all-cause mortality.Multivariable Cox regression was applied to evaluate the association between SGLT2i versus DPP4i with outcomes.Results:Initially,a total of 76147 diabetes patients treated with SGLT2i or DPP4i were identified.After matching,226 patients(mean age,65.5±7.6 years)were included(113 SGLT2i users versus 113 DPP4i users).During a median follow-up of 5.51 years,43(19.02%)patients developed composite MACE.Compared with DPP4i users,SGLT2i was not significantly associated with MACE[hazard ratio(HR):0.54;95%confidence interval(CI):0.27-1.10]in the adjusted model.For the secondary outcomes,breast cancer patients treated with SGLT2i presented with an 84%lower risk of stroke/TIA(HR:0.16;95%CI:0.04-0.61)than DPP4i users after adjustments.No significant associations were observed between SGLT2i with MI(HR:0.41;95%CI:0.10-1.69),cardiovascular mortality(HR:0.86;95%CI:0.20-3.70),all-cause mortality(0.51;95%CI:0.17-1.58),and heart failure(0.47;95%CI:0.12-1.89),in relation to DPP4i.Conclusion:SGLT2i was associated with lower risks of stroke/TIA in diabetic patients with breast cancer receiving AIs compared with DPP4i.
基金Tianjin Key Medical Discipline(Specialty)Construction Project,Grant/Award Number:TJYXZDXK-029ANational Natural Science Foundation of China,Grant/Award Numbers:82170327,82370332。
文摘Background:The role of surgery in metastatic breast cancer(MBC)is currently controversial.Several novel statistical and deep learning(DL)methods promise to infer the suitability of surgery at the individual level.Objective:The objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery required.Methods:We introduced the deep survival regression with mixture effects(DSME),a semi-parametric DL model integrating three causal inference methods.Six models were trained to make individualized treatment recommendations.Patients who received treatments in line with the DL models'recommendations were compared with those who underwent treatments divergent from the recommendations.Inverse probability weighting(IPW)was used to minimize bias.The effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal inference.Results:In total,5269 female patients with MBC were included.DSME was an independent protective factor,outperforming other models in recommend-ing surgery(IPW-adjusted hazard ratio[HR]=0.39,95%confidence interval[CI]:0.19–0.78)and type of surgery(IPW-adjusted HR=0.66,95%CI:0.48–0.93).DSME was superior to other models and traditional guidelines,suggesting a higher proportion of patients benefiting from surgery,especially breast-conserving surgery.The debiased effect of patient characteristics,including age,tumor size,metastatic sites,lymph node status,and breast cancer subtypes,on surgery decision was also quantified.Conclusions:Our findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery needed.This method can facilitate the development of efficient,reliable treatment recommendation systems and provide quantifiable evidence for decision-making.
基金Tianjin Key Medical Discipline(Specialty)Construction Project,Grant/Award N umber:TJY XZDXK-029ANational Natural Science Foundation of China,Grant/Award Numbers:81970270,82170327Tianjin Postgr aduate Scientific Research Innovation Projec,G rant/Award Number:2021YJSB278。
文摘Background Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies.However,its use is associated with dose-dependent cardiotoxicity,causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival.In this study,an animal model of doxorubicin-induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin-induced myocardial injury.This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro.Methods Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group.Body weight,echocardiography,surface electrocardiogram,and myocardial histomorphology were measured.The mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups(phosphate-buffered saline,doxorubicin,and doxorubicin with resveratrol).Results Compared to the control group,the doxorubicin group showed a lower body weight and higher systolic arterial pressure,associated with reduced left ventricular ejection fraction and left ventricular fractional shortening,prolonged PR interval,and QT interval.These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes,increased protein expression levels ofα-smooth muscle actin and caspase 3,and reduced protein expression levels of Mitofusin2(MFN2)and Sirtuin1(SIRT1).Compared to the doxorubicin group,doxorubicin+resveratrol treatment reduced caspase 3 and manganese superoxide dismutase,and increased MFN2 and SIRT1 expression levels.Conclusion Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion.Resveratrol ameliorates doxorubicin-induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function.
