Background and aim:There are still no clinically satisfactory therapy for PBC.This study was performed to assess the safety and efficacy of IAs for the therapy of PBC.Methods:Relevant studies were identified and selec...Background and aim:There are still no clinically satisfactory therapy for PBC.This study was performed to assess the safety and efficacy of IAs for the therapy of PBC.Methods:Relevant studies were identified and selected by searching PubMed,Web of Science and Cochrane Library databases.The primary outcome was defined as the need for mortality or liver transplantation.Adverse effects and liver biochemical variables were a secondary outcome.Results:Nine randomized controlled trials,involving six different treatment regimens with a total of 996 patients,were included in the analysis.On meta-analysis,IAs was not associated with a reduction in risk of mortality or liver transplantation(risk ratio[RR]:0.92,95% confidence interval[CI]:0.69-1.22,P=0.57,P=0%),and have resulted in more adverse effects(RR:1.44,95%CI:1.08-1.92,P=0.01,P=19%).Subgroup analysis showed that IAs monotherapy caused adverse effects such as diarrthea,abdominal pain,and renal insufficiency(RR:1.36,95% CI:1.01-1.82,P=0.04,P=48%).IAs therapy did not prominently improve markers of liver function except for alkaline phosphatases(weighted mean difference[WMD]:-0.38,95% CI:-0.62 to-0.14,P=0.002).Conclusions:IAs cannot reduce the risk of mortality or liver transplantation,whether in IAs monotherapy or combination therapy,and even be associated with more adverse effects.展开更多
BACKGROUND Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019(COVID-19)but its full correlation with COVID-19 infection remains unknown.AIM To identify acute pancreatitis’occurrence...BACKGROUND Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019(COVID-19)but its full correlation with COVID-19 infection remains unknown.AIM To identify acute pancreatitis’occurrence,clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19.METHODS A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19.Data were obtained from hospital electronic medical records.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab.RESULTS Four hundred and eight out of 1432(28.49%)patients who received a renal allograft developed COVID-19 disease.The analyzed cohort included 321 patients(57%males).One hundred and fifty patients(46.7%)received at least one dose of the anti-SARS-CoV-2 vaccine before the infection.One hundred twenty-five(39.1%)patients required hospitalization,141(44.1%)developed pneumonia and four patients(1.3%)required mechanical ventilation.Treatment included immunosuppression modification in 233 patients(77.1%)and remdesivir in 53 patients(16.6%),besides the other supportive measures.In the study cohort,only one transplant recipient(0.3%)developed acute pancreatitis during acute COVID-19,presenting with abdominal pain and significantly elevated pancreatic enzymes.She survived without complications with a stable kidney allograft function.CONCLUSION Although rare,acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients.The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.展开更多
BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the ...BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice.Ferroptosis,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell death.Therefore,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after transplantation.AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP.METHODS A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT.In vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were observed.The changes in mitochondrial structure were observed using electron microscopy.RESULTS With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,P<0.001),prolonged the survival time of the recipient rats(11.5 d vs 16 d,P<0.01),and reduced the infiltration rate of CD3+T cells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after LT.In vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous ions.It also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidative damage and ferroptosis of T cells.CONCLUSION Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+T cell ferroptosis,which makes it an effective immunosuppressive agent after LT.展开更多
BACKGROUND Podocyte infolding glomerulopathy(PIG)is a newly described and rare glomerular disease.To date,only approximately 40 cases have been reported globally.CASE SUMMARY A 26-year-old female patient presented to ...BACKGROUND Podocyte infolding glomerulopathy(PIG)is a newly described and rare glomerular disease.To date,only approximately 40 cases have been reported globally.CASE SUMMARY A 26-year-old female patient presented to our hospital with a complaint of intermittent edema of both lower limbs over the past 2 years.The patient was diagnosed with PIG.She was prescribed corticosteroid therapy in other hospitals during the initial stage,to which she had responded poorly and had developed femoral head necrosis.Therefore,we administered immunosuppressants,reninangiotensin system inhibitors,combined with traditional Chinese medicine.The patient was followed for 1 year,during which her clinical condition improved.CONCLUSION Integrated Chinese and Western medicine may be effective for PIG treatment,which requires active intervention to improve prognosis.展开更多
Metabolic disease,including diabetes mellitus,hypertension,dyslipidemia,obesity,and hyperuricemia,is a common complication after liver transplantation and a risk factor for cardiovascular disease and death.The develop...Metabolic disease,including diabetes mellitus,hypertension,dyslipidemia,obesity,and hyperuricemia,is a common complication after liver transplantation and a risk factor for cardiovascular disease and death.The development of metabolic disease is closely related to the side effects of immunosuppressants.Therefore,optimization of the immunosuppressive regimen is very important for the prevention and treatment of metabolic disease.The Chinese Society of Organ Transplantation has developed an expert consensus on the management of metabolic diseases in Chinese liver transplant recipients based on recent studies.Emphasis is placed on the risk factors of metabolic diseases,the effect of immunosuppressants on metabolic disease,and the prevention and treatment of metabolic diseases.展开更多
Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipie...Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.展开更多
Objective To investigate the clinical efficacy of mycophenolate mofetil(MMF) with low dose CsA for chronic rejection in primary cadaveric renal recipients. Methods A total of 8 renal recipients who were clinically d...Objective To investigate the clinical efficacy of mycophenolate mofetil(MMF) with low dose CsA for chronic rejection in primary cadaveric renal recipients. Methods A total of 8 renal recipients who were clinically diagnosed as chronic rejection were given triimmunosuppressive agents: MMF 1.5～2.0 g/d+ CsA 2 to 3 mg/kg*d-1 and pred 10 mg/d.Results Blood creatinine reduced to normal level and urine protein disappeared in five cases, blood creatinine and urine protein decreased obviously in two cases, and kidney function deteriorated in another patient 4 to 9 weeks after this strategy. No acute rejection episodes or liver damage occurred among these patients during treatment. White blood cells reduced in one case, but it improved after therapy. Conclusion MMF combined with low dose CsA can bring a considerable efficacy in reversing chronic rejection of renal recipients. This immunosuppressive strategy may be a useful routine in the treatment of chronic rejection.展开更多
<i>Cytomegalovirus</i> (CMV) and <i>Pneumocystis jirovecii</i> fungus are the main opportunistic microorganisms that affect transplanted individuals. Immunosuppressive drugs administered to pre...<i>Cytomegalovirus</i> (CMV) and <i>Pneumocystis jirovecii</i> fungus are the main opportunistic microorganisms that affect transplanted individuals. Immunosuppressive drugs administered to prevent organ rejection leave the immune system vulnerable to these infections. The present report is about a kidney transplanted patient using immunosuppressants who was diagnosed with cytomegalovirus and pneumocystosis requiring admission to the intensive care unit (ICU). Female patient, 57 years old, a kidney transplanted three years ago, with comorbidities, such as systemic arterial hypertension, hypertriglyceridemia and type 2 diabetes mellitus. She was admitted to the hospital in January 2020 with a history of diarrhea, cough, malaise and weight loss of seven kg in a month. She made continuous use of the immunosuppressants tacrolimus<sup>®</sup> and mycophenolate sodium (MFS). After five days of hospitalization, she was transferred to the ICU due to refractory diarrhea, worsening renal function and respiratory pattern, requiring mechanical ventilation. Chest tomography showed changes that led to the diagnostic hypothesis of CMV pneumonia or <i>Pneumocystis jirovecii</i>. Treatment with Ganciclovir<sup>®</sup> and Bactrim<sup>®</sup> was started. The bronchial lavage polymerase chain reaction test confirmed the infectious condition for CMV and <i>Pneumocystis jirovecii</i>. Despite the drug therapy instituted, there was no improvement in the infectious condition. The patient started to present a general and progressive worsening of the clinical picture with loss of renal graft function, respiratory failure, metabolic acidosis, hemodynamic instability and severe distributive shock, evolving to death. In the present report, it was observed that after late kidney transplantation the fragility of the immune system caused by the use of immunosuppressants contributed to the development of a severe infection with CMV and <i>Pneumocystis jirovecii</i>. Adjusting the doses of immunosuppressants to individual needs can be an important measure for maintaining the proper immune system and consequently avoiding late opportunistic infections and death outcomes.展开更多
With 185 million people chronically infected globally,hepatitis C is a leading bloodborne infection.All-oral regimens of direct acting agents have superior efficacy compared to the historical interferon-based regimens...With 185 million people chronically infected globally,hepatitis C is a leading bloodborne infection.All-oral regimens of direct acting agents have superior efficacy compared to the historical interferon-based regimens and are significantly more tolerable.However,trials of both types of regimens have often excluded patients on immunosuppressive medications for reasons other than organ transplantation.Yet,these patients-most often suffering from malignancy or autoimmune diseases-could stand to benefit from these treatments.In this study,we systematically review the literature on the treatment of hepatitis C in these neglected populations.Research on patients with organ transplants is more robust and this literature is reviewed here non-systematically.Our systematic review produced 2273 unique works,of which 56 met our inclusion criteria and were used in our review.The quality of data was low;only 3 of the 56 studies were randomized controlled trials.Sustained virologic response was reported sporadically.Interferon-containing regimens achieved this end-point at rates comparable to that in immunocompetent individuals.Severe adverse effects and death were rare.Data on all-oral regimens were sparse,but in the most robust study,rates of sustained virologic response were again comparable to immunocompetent individuals (40/41).Efficacy and safety of interferoncontaining regimens and all-oral regimens were similar to rates in immunocompetent individuals;however,there were few interventional trials.The large number of case reports and case series makes conclusions vulnerable to publication bias.While firm conclusions are challenging,given the dearth of high-quality studies,our results demonstrate that antiviral therapy can be safe and effective.The advent of all-oral regimens offers patients and clinicians greatly increased chances of cure and fewer side effects.Preliminary data reveal that these regimens may confer such benefits in immunosuppressed individuals as well.More prospective interventional trials would greatly benefit the many patients with chronic hepatitis C on immunosuppressive therapies.展开更多
Purpose:There were 10%e30%of patients with adult-onset septic arthritis(SA)exhibiting sterile synovial fluid(SF),and the uncertainty in the determining diagnosis of these patients posed a challenge in management.The p...Purpose:There were 10%e30%of patients with adult-onset septic arthritis(SA)exhibiting sterile synovial fluid(SF),and the uncertainty in the determining diagnosis of these patients posed a challenge in management.The purpose of this study was to investigate the differences between confirmed(Newman A)and suspected(Newman B&C)SA in adults.Methods:This was a descriptive study with a cross-sectional study design conducted at a tertiary referral centre from July 2016 to February 2019.Patients aged over 18 years presented to the emergency department with clinical features suggestive of SA and were scheduled to undergo arthrotomy and joint lavage by the treating surgeon were included in the study.Patients with prosthetic joint infections and open joint injuries were excluded.Patients’demographic data,clinical features and laboratory parameters were collected.The clinical and laboratory profile(blood and SF)of the adult patients presenting with features suggestive of SA based on Newman criteria was statistically analyzed by SPSS version 20 software and Microsoft Excel.The categorical variables were expressed as proportions while the continuous variables were expressed as mean(SD)or median(IQR)depending upon the normality of distribution.The difference between the two groups for categorical variables was assessed using the Chisquare test and the difference for continuous variables was assessed using the unpaired t-test and the Mann-Whitney test depending upon normality.A p value<0.05 was considered significant.Results:Thirty-six patients were divided into confirmed(n¼19)or suspected(n¼17)SA for assessment based on SF culture.The median(IQR)age of the patients was 50 years(37e60 years).There was no significant difference in demographic,clinical and laboratory parameters between the concerned groups.Eight patients presented with fever.Among the confirmed SA cases,8 were negative for C-reactive protein and 6 had synovial white blood cell count<50,000.Staphylococcus species were isolated in 8 cases.The most common risk factors for SA were chronic kidney disease(25.0%),diabetes mellitus(25.0%),pharmacologic immunosuppression(16.7%),recent joint surgery(11.1%)and distant site infection(11.1%).Conclusion:SA is an orthopaedic emergency that needs prompt and aggressive treatment to prevent catastrophic complications.Confirmed and suspected cases of SA exhibit similar demography,clinical features and laboratory parameters at presentation which may mislead the treating surgeon.Management should be based on sound clinical judgment in the event of failure to culture microorganisms.展开更多
The ongoing coronavirus disease-2019(COVID-19)pandemic has necessitated special considerations in the management of diseases.The way presence of pre-existing diseases or treatment for it predisposes to,alters course o...The ongoing coronavirus disease-2019(COVID-19)pandemic has necessitated special considerations in the management of diseases.The way presence of pre-existing diseases or treatment for it predisposes to,alters course of,and changes the management of COVID-19,is of relevance and is being extensively studied.Autoimmune hepatitis(AIH)is unique in that it is an autoimmune disease mandating treatment with immunosuppressive drugs,as well as a liver disease with potential for varying degrees of underlying fibrosis.The use of immunosuppressive drugs could alter the risk of acquiring COVID-19,the clinical course and severity of COVID-19 and the degree of underlying liver fibrosis could alter the clinical outcomes of patients with COVID-19.In this review,we try to summarize key areas relevant in understanding and improving the clinical care of patients with AIH in the current pandemic.Special considerations required in the management of patients with AIH in COVID-19 hotspots have been outlined based on the current evidence.展开更多
文摘Background and aim:There are still no clinically satisfactory therapy for PBC.This study was performed to assess the safety and efficacy of IAs for the therapy of PBC.Methods:Relevant studies were identified and selected by searching PubMed,Web of Science and Cochrane Library databases.The primary outcome was defined as the need for mortality or liver transplantation.Adverse effects and liver biochemical variables were a secondary outcome.Results:Nine randomized controlled trials,involving six different treatment regimens with a total of 996 patients,were included in the analysis.On meta-analysis,IAs was not associated with a reduction in risk of mortality or liver transplantation(risk ratio[RR]:0.92,95% confidence interval[CI]:0.69-1.22,P=0.57,P=0%),and have resulted in more adverse effects(RR:1.44,95%CI:1.08-1.92,P=0.01,P=19%).Subgroup analysis showed that IAs monotherapy caused adverse effects such as diarrthea,abdominal pain,and renal insufficiency(RR:1.36,95% CI:1.01-1.82,P=0.04,P=48%).IAs therapy did not prominently improve markers of liver function except for alkaline phosphatases(weighted mean difference[WMD]:-0.38,95% CI:-0.62 to-0.14,P=0.002).Conclusions:IAs cannot reduce the risk of mortality or liver transplantation,whether in IAs monotherapy or combination therapy,and even be associated with more adverse effects.
文摘BACKGROUND Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019(COVID-19)but its full correlation with COVID-19 infection remains unknown.AIM To identify acute pancreatitis’occurrence,clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19.METHODS A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19.Data were obtained from hospital electronic medical records.Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab.RESULTS Four hundred and eight out of 1432(28.49%)patients who received a renal allograft developed COVID-19 disease.The analyzed cohort included 321 patients(57%males).One hundred and fifty patients(46.7%)received at least one dose of the anti-SARS-CoV-2 vaccine before the infection.One hundred twenty-five(39.1%)patients required hospitalization,141(44.1%)developed pneumonia and four patients(1.3%)required mechanical ventilation.Treatment included immunosuppression modification in 233 patients(77.1%)and remdesivir in 53 patients(16.6%),besides the other supportive measures.In the study cohort,only one transplant recipient(0.3%)developed acute pancreatitis during acute COVID-19,presenting with abdominal pain and significantly elevated pancreatic enzymes.She survived without complications with a stable kidney allograft function.CONCLUSION Although rare,acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients.The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.
基金Supported by National Key Research and Development Program of China,No.2020YFA0710802The Youth Science Fund of the Nature Science Foundation of Tianjin,No.20JCQNJC01370+1 种基金The Key Projects of Tianjin Science and Technology Project,No.21JCZDJC00160The Science Foundation of Tianjin Health Commission,No.ZC20065 and No.ZC20089.
文摘BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice.Ferroptosis,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell death.Therefore,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after transplantation.AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP.METHODS A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT.In vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were observed.The changes in mitochondrial structure were observed using electron microscopy.RESULTS With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,P<0.001),prolonged the survival time of the recipient rats(11.5 d vs 16 d,P<0.01),and reduced the infiltration rate of CD3+T cells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after LT.In vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous ions.It also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidative damage and ferroptosis of T cells.CONCLUSION Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+T cell ferroptosis,which makes it an effective immunosuppressive agent after LT.
文摘BACKGROUND Podocyte infolding glomerulopathy(PIG)is a newly described and rare glomerular disease.To date,only approximately 40 cases have been reported globally.CASE SUMMARY A 26-year-old female patient presented to our hospital with a complaint of intermittent edema of both lower limbs over the past 2 years.The patient was diagnosed with PIG.She was prescribed corticosteroid therapy in other hospitals during the initial stage,to which she had responded poorly and had developed femoral head necrosis.Therefore,we administered immunosuppressants,reninangiotensin system inhibitors,combined with traditional Chinese medicine.The patient was followed for 1 year,during which her clinical condition improved.CONCLUSION Integrated Chinese and Western medicine may be effective for PIG treatment,which requires active intervention to improve prognosis.
基金National Science and Technology Major Project of China,No.2017ZX10203205National Natural Science Funds for Distinguished Young Scholar of China,No.81625003National Natural Science Foundation of China,No.81930016.
文摘Metabolic disease,including diabetes mellitus,hypertension,dyslipidemia,obesity,and hyperuricemia,is a common complication after liver transplantation and a risk factor for cardiovascular disease and death.The development of metabolic disease is closely related to the side effects of immunosuppressants.Therefore,optimization of the immunosuppressive regimen is very important for the prevention and treatment of metabolic disease.The Chinese Society of Organ Transplantation has developed an expert consensus on the management of metabolic diseases in Chinese liver transplant recipients based on recent studies.Emphasis is placed on the risk factors of metabolic diseases,the effect of immunosuppressants on metabolic disease,and the prevention and treatment of metabolic diseases.
基金supported by grants from the National S&T Major Project (2017ZX10203205)Key Program,National Natural Science Foundation of China (81930016)Zhejiang Provincial Natural Science Foundation of China (LY21H160026)。
文摘Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.
文摘Objective To investigate the clinical efficacy of mycophenolate mofetil(MMF) with low dose CsA for chronic rejection in primary cadaveric renal recipients. Methods A total of 8 renal recipients who were clinically diagnosed as chronic rejection were given triimmunosuppressive agents: MMF 1.5～2.0 g/d+ CsA 2 to 3 mg/kg*d-1 and pred 10 mg/d.Results Blood creatinine reduced to normal level and urine protein disappeared in five cases, blood creatinine and urine protein decreased obviously in two cases, and kidney function deteriorated in another patient 4 to 9 weeks after this strategy. No acute rejection episodes or liver damage occurred among these patients during treatment. White blood cells reduced in one case, but it improved after therapy. Conclusion MMF combined with low dose CsA can bring a considerable efficacy in reversing chronic rejection of renal recipients. This immunosuppressive strategy may be a useful routine in the treatment of chronic rejection.
文摘<i>Cytomegalovirus</i> (CMV) and <i>Pneumocystis jirovecii</i> fungus are the main opportunistic microorganisms that affect transplanted individuals. Immunosuppressive drugs administered to prevent organ rejection leave the immune system vulnerable to these infections. The present report is about a kidney transplanted patient using immunosuppressants who was diagnosed with cytomegalovirus and pneumocystosis requiring admission to the intensive care unit (ICU). Female patient, 57 years old, a kidney transplanted three years ago, with comorbidities, such as systemic arterial hypertension, hypertriglyceridemia and type 2 diabetes mellitus. She was admitted to the hospital in January 2020 with a history of diarrhea, cough, malaise and weight loss of seven kg in a month. She made continuous use of the immunosuppressants tacrolimus<sup>®</sup> and mycophenolate sodium (MFS). After five days of hospitalization, she was transferred to the ICU due to refractory diarrhea, worsening renal function and respiratory pattern, requiring mechanical ventilation. Chest tomography showed changes that led to the diagnostic hypothesis of CMV pneumonia or <i>Pneumocystis jirovecii</i>. Treatment with Ganciclovir<sup>®</sup> and Bactrim<sup>®</sup> was started. The bronchial lavage polymerase chain reaction test confirmed the infectious condition for CMV and <i>Pneumocystis jirovecii</i>. Despite the drug therapy instituted, there was no improvement in the infectious condition. The patient started to present a general and progressive worsening of the clinical picture with loss of renal graft function, respiratory failure, metabolic acidosis, hemodynamic instability and severe distributive shock, evolving to death. In the present report, it was observed that after late kidney transplantation the fragility of the immune system caused by the use of immunosuppressants contributed to the development of a severe infection with CMV and <i>Pneumocystis jirovecii</i>. Adjusting the doses of immunosuppressants to individual needs can be an important measure for maintaining the proper immune system and consequently avoiding late opportunistic infections and death outcomes.
文摘With 185 million people chronically infected globally,hepatitis C is a leading bloodborne infection.All-oral regimens of direct acting agents have superior efficacy compared to the historical interferon-based regimens and are significantly more tolerable.However,trials of both types of regimens have often excluded patients on immunosuppressive medications for reasons other than organ transplantation.Yet,these patients-most often suffering from malignancy or autoimmune diseases-could stand to benefit from these treatments.In this study,we systematically review the literature on the treatment of hepatitis C in these neglected populations.Research on patients with organ transplants is more robust and this literature is reviewed here non-systematically.Our systematic review produced 2273 unique works,of which 56 met our inclusion criteria and were used in our review.The quality of data was low;only 3 of the 56 studies were randomized controlled trials.Sustained virologic response was reported sporadically.Interferon-containing regimens achieved this end-point at rates comparable to that in immunocompetent individuals.Severe adverse effects and death were rare.Data on all-oral regimens were sparse,but in the most robust study,rates of sustained virologic response were again comparable to immunocompetent individuals (40/41).Efficacy and safety of interferoncontaining regimens and all-oral regimens were similar to rates in immunocompetent individuals;however,there were few interventional trials.The large number of case reports and case series makes conclusions vulnerable to publication bias.While firm conclusions are challenging,given the dearth of high-quality studies,our results demonstrate that antiviral therapy can be safe and effective.The advent of all-oral regimens offers patients and clinicians greatly increased chances of cure and fewer side effects.Preliminary data reveal that these regimens may confer such benefits in immunosuppressed individuals as well.More prospective interventional trials would greatly benefit the many patients with chronic hepatitis C on immunosuppressive therapies.
文摘Purpose:There were 10%e30%of patients with adult-onset septic arthritis(SA)exhibiting sterile synovial fluid(SF),and the uncertainty in the determining diagnosis of these patients posed a challenge in management.The purpose of this study was to investigate the differences between confirmed(Newman A)and suspected(Newman B&C)SA in adults.Methods:This was a descriptive study with a cross-sectional study design conducted at a tertiary referral centre from July 2016 to February 2019.Patients aged over 18 years presented to the emergency department with clinical features suggestive of SA and were scheduled to undergo arthrotomy and joint lavage by the treating surgeon were included in the study.Patients with prosthetic joint infections and open joint injuries were excluded.Patients’demographic data,clinical features and laboratory parameters were collected.The clinical and laboratory profile(blood and SF)of the adult patients presenting with features suggestive of SA based on Newman criteria was statistically analyzed by SPSS version 20 software and Microsoft Excel.The categorical variables were expressed as proportions while the continuous variables were expressed as mean(SD)or median(IQR)depending upon the normality of distribution.The difference between the two groups for categorical variables was assessed using the Chisquare test and the difference for continuous variables was assessed using the unpaired t-test and the Mann-Whitney test depending upon normality.A p value<0.05 was considered significant.Results:Thirty-six patients were divided into confirmed(n¼19)or suspected(n¼17)SA for assessment based on SF culture.The median(IQR)age of the patients was 50 years(37e60 years).There was no significant difference in demographic,clinical and laboratory parameters between the concerned groups.Eight patients presented with fever.Among the confirmed SA cases,8 were negative for C-reactive protein and 6 had synovial white blood cell count<50,000.Staphylococcus species were isolated in 8 cases.The most common risk factors for SA were chronic kidney disease(25.0%),diabetes mellitus(25.0%),pharmacologic immunosuppression(16.7%),recent joint surgery(11.1%)and distant site infection(11.1%).Conclusion:SA is an orthopaedic emergency that needs prompt and aggressive treatment to prevent catastrophic complications.Confirmed and suspected cases of SA exhibit similar demography,clinical features and laboratory parameters at presentation which may mislead the treating surgeon.Management should be based on sound clinical judgment in the event of failure to culture microorganisms.
文摘The ongoing coronavirus disease-2019(COVID-19)pandemic has necessitated special considerations in the management of diseases.The way presence of pre-existing diseases or treatment for it predisposes to,alters course of,and changes the management of COVID-19,is of relevance and is being extensively studied.Autoimmune hepatitis(AIH)is unique in that it is an autoimmune disease mandating treatment with immunosuppressive drugs,as well as a liver disease with potential for varying degrees of underlying fibrosis.The use of immunosuppressive drugs could alter the risk of acquiring COVID-19,the clinical course and severity of COVID-19 and the degree of underlying liver fibrosis could alter the clinical outcomes of patients with COVID-19.In this review,we try to summarize key areas relevant in understanding and improving the clinical care of patients with AIH in the current pandemic.Special considerations required in the management of patients with AIH in COVID-19 hotspots have been outlined based on the current evidence.
