Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogenei...Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer.NEPC may arise de novo or develop following androgen deprivation therapy(ADT).NEPC that arise following ADT has the nomenclature“treatmentemerging/induced NEPC(t-NEPC)”.t-NEPC would be anticipated in castration resistant prostate cancer(CRPC)and metastatic PCa.t-NEPC is characterized by low or absent androgen receptor(AR)expression,independence of AR signaling,and gain of neuroendocrine phenotype.t-NEPC is an aggressive metastatic tumor,develops from PCa in response to drug induced ADT,and shows very short response to conventional therapy.t-NEPC occurs in 10%-17%of patients with CRPC.De novo NEPC is rare and is accounting for less than 2%of all PCa.The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated.Sphingosine kinase 1 plays a significant role in t-NEPC development.Although neuroendocrine markers:Synaptophysin,chromogranin A,and insulinoma associated protein 1(INSM1)are expressed in t-NEPC,they are non-specific for diagnosis,prognosis,and follow-up of therapy.t-NEPC shows enriched genomic alteration in tumor protein P53(TP53)and retinoblastoma 1(RB1).There are evidences suggest that t-NEPC might develop through epigenetic evolution.There are genomic,epigenetic,and transcriptional alterations that are reported to be involved in development of t-NEPC.Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC.PCa is resistant to immunotherapy,and at present there are running trials to approach immunotherapy for PCa,CRPC,and t-NEPC.展开更多
While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a p...While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.展开更多
Introduction Thrombosis is the formation of a blood clot in a blood vessel. When thrombosis happens in the brain,it would cause stroke; when happens in the heart,it would cause heart attack. If a thrombus breaks and t...Introduction Thrombosis is the formation of a blood clot in a blood vessel. When thrombosis happens in the brain,it would cause stroke; when happens in the heart,it would cause heart attack. If a thrombus breaks and travels to the lung,it would展开更多
Background Induction therapy are utilized to achieve an adequate immunosuppression at the time of transplantation. The use of basiliximab or anti-thymocyte globulin （ATG） for induction therapy has significantly redu...Background Induction therapy are utilized to achieve an adequate immunosuppression at the time of transplantation. The use of basiliximab or anti-thymocyte globulin （ATG） for induction therapy has significantly reduced the incidence of acute rejection episodes post-transplantation. The purpose of this study was to compare the efficacy and safety of the basiliximab in patients with immuno-induction therapy after kidney transplantation with the ATG. Methods A retrospective analysis was carried out in kidney transplant recipients including 146 patients with the basiliximab and 116 cases with the ATG and the acute rejection, graft function, infective complications and 1-year and 5-year actuarial patient and graft survival after renal transplantation were compared between the two treatment groups. Results There were no statistically significant difference between groups regarding age, sex, cold ischemic time, warm ischemic time, human leukocyte antigen （HLA） matching type between the donor and recipient, lymphotoxin test and the use of immunosuppressive agents. There was no statistical significance regarding the incidence of the acute rejection （9.59% vs. 8.62%, P=0.481） and delayed graft function （10.27% vs. 9.48%, P=0.501） between groups. There were significantly lower lung infection incidence （5.48% vs. 12.93%, P=0.029） in the basiliximab-treated group in comparison with the ATG-treated group. One-year patient and graft survival rates were 98%, 97% for the basiliximab-treated group, and 95%, 73% for the ATG-treated group, respectively. Five-year patient and graft survival rates were 92%, 86% for the basiliximab-treated group and 93%, 72% for the ATG-treated group, respectively. Log rank test showed statistically significant difference with P=0.038 for patients and P=-0.033 for grafts, respectively. There were significantly lower the incidence of granulocytopenia （8.22% vs. 17.24%, P=0.022） and thrombocytopenia （4.11% vs. 19.83%, P=0.000） after transplantation in the basiliximab-treated group in comparison with the ATG-treated group. There was no statistical significance regarding the incidence of the heart dysfunction after transplantation between the two groups （6.16% vs. 6.90%, P=0.502）. Conclusion The immuno-induction therapy with the basiliximab in kidney transplant recipients is efficient and safe with less complication compared with the ATG.展开更多
Although hepatitis B virus(HBV)reactivation has been reported in hepatitis C patients who received interferon therapy,rare cases of HBV reactivation occur in the context of direct-acting antiviral(DAA)agent therapy fo...Although hepatitis B virus(HBV)reactivation has been reported in hepatitis C patients who received interferon therapy,rare cases of HBV reactivation occur in the context of direct-acting antiviral(DAA)agent therapy for treatment of hepatitis C virus(HCV)infection.Recent studies observed that the reactivations were predominantly in hepatitis B surface antigen(HBsAg)positive patients,but reactivation can rarely occur in patients who are HBsAg negative and hepatitis B core antibody(HBcAb)positive.The severity of an HBV flare varies.In some cases,severe liver injury or fulminant hepatic failure may occur.HBV reactivation may occur regardless of HCV genotype and type of DAA regimens.The onset of HBV reactivation can range from 4 to 48 weeks after initiating DAA therapy.These patients may have undetectable levels of HBV deoxyribonucleic acid(DNA)prior to DAA treatment.Pre-emptive antiviral therapy for HBV should be considered in HBsAg-positive patients with high levels of viremia who are not receiving HBV treatment.If HBV DNA viral load is less than the guideline criteria for HBV treatment,one should consider pre-emptive HBV antiviral versus HBV DNA monitoring during DAA therapy.For patients who are HBsAg negative but HBcAb positive,close monitoring of serum alanine aminotransferase(ALT)levels during/post-treatment is highly recommended.The current review summarizes the recommendations of different society guidelines and discusses the appropriate management strategies in various patient profiles.展开更多
文摘Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer.NEPC may arise de novo or develop following androgen deprivation therapy(ADT).NEPC that arise following ADT has the nomenclature“treatmentemerging/induced NEPC(t-NEPC)”.t-NEPC would be anticipated in castration resistant prostate cancer(CRPC)and metastatic PCa.t-NEPC is characterized by low or absent androgen receptor(AR)expression,independence of AR signaling,and gain of neuroendocrine phenotype.t-NEPC is an aggressive metastatic tumor,develops from PCa in response to drug induced ADT,and shows very short response to conventional therapy.t-NEPC occurs in 10%-17%of patients with CRPC.De novo NEPC is rare and is accounting for less than 2%of all PCa.The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated.Sphingosine kinase 1 plays a significant role in t-NEPC development.Although neuroendocrine markers:Synaptophysin,chromogranin A,and insulinoma associated protein 1(INSM1)are expressed in t-NEPC,they are non-specific for diagnosis,prognosis,and follow-up of therapy.t-NEPC shows enriched genomic alteration in tumor protein P53(TP53)and retinoblastoma 1(RB1).There are evidences suggest that t-NEPC might develop through epigenetic evolution.There are genomic,epigenetic,and transcriptional alterations that are reported to be involved in development of t-NEPC.Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC.PCa is resistant to immunotherapy,and at present there are running trials to approach immunotherapy for PCa,CRPC,and t-NEPC.
文摘While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.
基金supported by the National Science Foundation CAREER Award CBET-0133775 and CBET-0754158,REU grant,and graduate fellowship from the CUNY
文摘Introduction Thrombosis is the formation of a blood clot in a blood vessel. When thrombosis happens in the brain,it would cause stroke; when happens in the heart,it would cause heart attack. If a thrombus breaks and travels to the lung,it would
文摘Background Induction therapy are utilized to achieve an adequate immunosuppression at the time of transplantation. The use of basiliximab or anti-thymocyte globulin （ATG） for induction therapy has significantly reduced the incidence of acute rejection episodes post-transplantation. The purpose of this study was to compare the efficacy and safety of the basiliximab in patients with immuno-induction therapy after kidney transplantation with the ATG. Methods A retrospective analysis was carried out in kidney transplant recipients including 146 patients with the basiliximab and 116 cases with the ATG and the acute rejection, graft function, infective complications and 1-year and 5-year actuarial patient and graft survival after renal transplantation were compared between the two treatment groups. Results There were no statistically significant difference between groups regarding age, sex, cold ischemic time, warm ischemic time, human leukocyte antigen （HLA） matching type between the donor and recipient, lymphotoxin test and the use of immunosuppressive agents. There was no statistical significance regarding the incidence of the acute rejection （9.59% vs. 8.62%, P=0.481） and delayed graft function （10.27% vs. 9.48%, P=0.501） between groups. There were significantly lower lung infection incidence （5.48% vs. 12.93%, P=0.029） in the basiliximab-treated group in comparison with the ATG-treated group. One-year patient and graft survival rates were 98%, 97% for the basiliximab-treated group, and 95%, 73% for the ATG-treated group, respectively. Five-year patient and graft survival rates were 92%, 86% for the basiliximab-treated group and 93%, 72% for the ATG-treated group, respectively. Log rank test showed statistically significant difference with P=0.038 for patients and P=-0.033 for grafts, respectively. There were significantly lower the incidence of granulocytopenia （8.22% vs. 17.24%, P=0.022） and thrombocytopenia （4.11% vs. 19.83%, P=0.000） after transplantation in the basiliximab-treated group in comparison with the ATG-treated group. There was no statistical significance regarding the incidence of the heart dysfunction after transplantation between the two groups （6.16% vs. 6.90%, P=0.502）. Conclusion The immuno-induction therapy with the basiliximab in kidney transplant recipients is efficient and safe with less complication compared with the ATG.
文摘Although hepatitis B virus(HBV)reactivation has been reported in hepatitis C patients who received interferon therapy,rare cases of HBV reactivation occur in the context of direct-acting antiviral(DAA)agent therapy for treatment of hepatitis C virus(HCV)infection.Recent studies observed that the reactivations were predominantly in hepatitis B surface antigen(HBsAg)positive patients,but reactivation can rarely occur in patients who are HBsAg negative and hepatitis B core antibody(HBcAb)positive.The severity of an HBV flare varies.In some cases,severe liver injury or fulminant hepatic failure may occur.HBV reactivation may occur regardless of HCV genotype and type of DAA regimens.The onset of HBV reactivation can range from 4 to 48 weeks after initiating DAA therapy.These patients may have undetectable levels of HBV deoxyribonucleic acid(DNA)prior to DAA treatment.Pre-emptive antiviral therapy for HBV should be considered in HBsAg-positive patients with high levels of viremia who are not receiving HBV treatment.If HBV DNA viral load is less than the guideline criteria for HBV treatment,one should consider pre-emptive HBV antiviral versus HBV DNA monitoring during DAA therapy.For patients who are HBsAg negative but HBcAb positive,close monitoring of serum alanine aminotransferase(ALT)levels during/post-treatment is highly recommended.The current review summarizes the recommendations of different society guidelines and discusses the appropriate management strategies in various patient profiles.
