Efficacy and safety of carrimycin in ten patients with severe pneumonia following solid organ transplantation

BACKGROUND The number of patients undergoing solid organ transplantation has increased annually.However,infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of immunosuppressants.Carrimycin is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4’’-O-isovaleryltransferase gene(ist)from streptomyces thermotoleran.Carrimycin has good antibacterial and antiviral effects.However,no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia(SP)after solid organ transplantation.AIM To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical treatment.METHODS In March 2022,ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March 2022.When the condition was critical and difficult to control with other drugs,carrimycin was administered.These ten patients'clinical features and treatment protocols were retrospectively analyzed,and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were evaluated.RESULTS All ten patients were included in the analysis.Regarding etiological agent detection,there were three cases of fungal pneumonia,two cases of bacterial pneumonia,two cases of Pneumocystis pneumonia,and three cases of mixed infections.After treatment with carrimycin,the disease in seven patients significantly improved,the course of the disease was significantly shortened,fever was quickly controlled,chest computed tomography was significantly improved,and oxygenation was significantly improved.Finally,the patients were discharged after curing.One patient died of acute respiratory distress syndrome,and two patients discontinued treatment.CONCLUSION Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation.Carrimycin may have antibacterial and antiviral effects in patients with SP following solid organ transplantation.

Considerations for the use of porcine organ donation models in preclinical organ donor intervention research

Use of animal models in preclinical transplant research is essential to the optimization of human allografts for clinical transplantation.Animal models of organ donation and preservation help to advance and improve technical elements of solid organ recovery and facilitate research of ischemia-reperfusion injury,organ preservation strategies,and future donor-based interventions.Important considerations include cost,public opinion regarding the conduct of animal research,translational value,and relevance of the animal model for clinical practice.We present an overview of two porcine models of organ donation:donation following brain death(DBD)and donation following circulatory death(DCD).The cardiovascular anatomy and physiology of pigs closely resembles those of humans,making this species the most appropriate for pre-clinical research.Pigs are also considered a potential source of organs for human heart and kidney xenotransplantation.It is imperative to minimize animal loss during procedures that are surgically complex.We present our experience with these models and describe in detail the use cases,procedural approach,challenges,alternatives,and limitations of each model.

Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation.Furthermore,no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.CONCLUSION The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies,and its application in solid organ transplantation,is yet to be confirmed in clinical studies.Thus,the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.

Vaccination for solid organ transplanted patients:Recommendations,efficacy,and safety

Solid organ transplant recipients face unique challenges in managing their im-munosuppressed status,making vaccination a critical consideration.This review aimed to comprehensively analyze current recommendations,evaluate the effi-cacy of vaccinations in this population,and assess safety concerns.We explored the latest evidence on vaccine types,timing,and potential benefits for transplant patients,highlighting the importance of individualized approaches for routinely used vaccines as well as coronavirus disease 2019 vaccines.By synthesizing avai-lable data,this review underscored the pressing need to optimize vaccination strategies,ensuring that transplant recipients can obtain the full protection against many pathogens while minimizing risks associated with their post-transplant immunosuppression.

China organ donation and transplantation update: the Hangzhou Resolution

The much-anticipated change in the practice of organ donation and transplantation in China is now underway and affirmed by an important Hangzhou Resolution promulgated at the 2013 China Transplant Congress.Support of the National Health and Family Planning Commission On October 29,2013,in a meeting of the National Health and Family Planning Commission (NHFPC)officials with Jie-Fu Huang,Head of National Organ Transplant Committee(OTC), Hai-Bo Wang,Director of China Organ Transplant Response System (COTRS)

Advances in Cryopreservation of Organs

Organ transplantation is an effective approach for the treatment of end-stage organ failures. Currently, the donor organs used for clinical transplantation are all preserved at above-zero temperatures. These preservation methods are well-established and simple but the storage time lasts for only 4–12 h. Some researchers tried to extend the organ storage time by improving protectant and HLA matching to raise the use of stored organs and prolong the long-term survival of organs. These efforts still fall short of the clinical demand for organ transplantation. Moreover, a great many organs were wasted due to limited storage time, HLA mismatch, patients＇ conditions or distance involved. Therefore, preserving organs for several weeks or even months and establishing Organ Bank are the tough challenges and have become a shared goal of global scholars. This article reviews some issues involved in the cryopreservation of organs, such as use of cryoprotecting agents, freezing and thawing methods in the cryopreservation of hearts, kidneys and other organs.

Current status of glucocorticoid usage in solid organ transplantation

Glucocorticoids(GCs)have been the mainstay of immunosuppressive therapy in solid organ transplantation(SOT)for decades,due to their potent effects on innate immunity and tissue protective effects.However,some SOT centers are reluctant to administer GCs long-term because of the various related side effects.This review summarizes the advantages and disadvantages of GCs in SOT.PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes covering“transplantation”and“glucocorticoids”.GCs are used in transplant recipients,transplant donors,and organ perfusate solution to improve transplant outcomes.In SOT recipients,GCs are administered as induction and maintenance immunosuppressive therapy.GCs are also the cornerstone to treat acute antibody-and T-cell-mediated rejections.Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols,to reduce ischemia-reperfusion injury peri-transplant.GCs with low bioavailability and high potency for GC receptors,such as budesonide,nanoparticle-mediated targeted delivery of GCs to specific organs,and combination use of dexamethasone with inducers of immuneregulatory cells,are new methods of GC application in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression.Various side effects involving different non-targeted organs/tissues,such as bone,cardiovascular,neuromuscular,skin and gastrointestinal tract,have been noted for GCs.There are also potential drug-drug interactions for GCs in SOT patients.

Hepatitis E in solid organ transplant recipients:A systematic review and meta-analysis

BACKGROUND Hepatitis E virus(HEV)infection is underdiagnosed due to the use of serological assays with low sensitivity.Although most patients with HEV recover completely,HEV infection among patients with pre-existing chronic liver disease and organ-transplant recipients on immunosuppressive therapy can result in decompensated liver disease and death.AIM To demonstrate the prevalence of HEV infection in solid organ transplant(SOT)recipients.METHODS We searched Ovid MEDLINE,EMBASE,and the Cochrane Library for eligible articles through October 2020.The inclusion criteria consisted of adult patients with history of SOT.HEV infection is confirmed by either HEV-immunoglobulin G,HEV-immunoglobulin M,or HEV RNA assay.RESULTS Of 563 citations,a total of 22 studies(n=4557)were included in this metaanalysis.The pooled estimated prevalence of HEV infection in SOT patients was 20.2%[95%confidence interval(CI):14.9-26.8].The pooled estimated prevalence of HEV infection for each organ transplant was as follows:liver(27.2%;95%CI:20.0-35.8),kidney(12.8%;95%CI:9.3-17.3),heart(12.8%;95%CI:9.3-17.3),and lung(5.6%;95%CI:1.6-17.9).Comparison across organ transplants demonstrated statistical significance(Q=16.721,P=0.002).The subgroup analyses showed that the prevalence of HEV infection among SOT recipients was significantly higher in middle-income countries compared to high-income countries.The pooled estimated prevalence of de novo HEV infection was 5.1%(95%CI:2.6-9.6)and the pooled estimated prevalence of acute HEV infection was 4.3%(95%CI:1.9-9.4).CONCLUSION HEV infection is common in SOT recipients,particularly in middle-income countries.The prevalence of HEV infection in lung transplant recipients is considerably less common than other organ transplants.More studies examining the clinical impacts of HEV infection in SOT recipients,such as graft failure,rejection,and mortality are warranted.

Impact of immunosuppression on incidence of post-transplant diabetes mellitus in solid organ transplant recipients:Systematic review and meta-analysis

BACKGROUND Solid organ transplantation is a life-saving intervention for end-stage organ disease.Post-transplant diabetes mellitus(PTDM)is a common complication in solid organ transplant recipients,and significantly compromises long-term survival beyond a year.AIM To perform a systematic review and meta-analysis to estimate incidence of PTDM and compare the effects of the 3 major immunosuppressants on incidence of PTDM.METHODS Two hundred and six eligible studies identified 75595 patients on Tacrolimus,51242 on Cyclosporine and 3020 on Sirolimus.Random effects meta-analyses was used to calculate incidence.RESULTS Network meta-analysis estimated the overall risk of developing PTDM was higher with tacrolimus(OR=1.495%CI:1.0–2.0)and sirolimus(OR=1.8;95%CI:1.5–2.2)than with Cyclosporine.The overall incidence of PTDM at years 2-3 was 17%for kidney,19%for liver and 22%for heart.The risk factors for PTDM most frequently identified in the primary studies were age,body mass index,hepatitis C,and African American descent.CONCLUSION Tacrolimus tends to exhibit higher diabetogenicity in the short-term(2-3 years post-transplant),whereas sirolimus exhibits higher diabetogenicity in the longterm(5-10 years post-transplant).This study will aid clinicians in recognition of risk factors for PTDM and encourage careful evaluation of the risk/benefit of different immunosuppressant regimens in transplant recipients.

Liver transplantation using organs from deceased organ donors: a single organ transplant center experience

BACKGROUND： In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program.METHODS： From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized retrospectively.RESULTS： Among the 29 donors, 24 were China Category II donors（organ donation after cardiac death）, and five were China Category III donors（organ donation after brain death followed by cardiac death）. The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422（2-696） days. Among the five mortalities during the follow-up,three died of tumor recurrence. In terms of post-transplant complications, 9 recipients（34.6%） experienced early allograft dysfunction, 1（3.8%） had non-anastomotic biliary stricture,and 1（3.8%） was complicated with hepatic arterial thrombosis.None of these complications resulted in patient death. Notably,primary non-function was not observed in any of the grafts.CONCLUSION： With careful donor selection, liver transplant from deceased donors can be performed safely and plays acritical role in overcoming the extreme organ shortage in China.

Impact of tacrolimus intra-patient variability in adverse outcomes after organ transplantation

Tacrolimus(Tac)is currently the most common calcineurin-inhibitor employed in solid organ transplantation.High intra-patient variability(IPV)of Tac(Tac IPV)has been associated with an increased risk of immune-mediated rejection and poor outcomes after kidney transplantation.Few data are available concerning the impact of high Tac IPV in non-kidney transplants.However,even in kidney transplantation,there is still a controversy whether high Tac IPV is indeed detrimental in respect to graft and/or patient survival.This may be due to different methods employed to evaluate IPV and distinct time frames adopted to assess graft and patient survival in those reports published up to now in the literature.Little is also known about the influence of high Tac IPV in the development of other untoward adverse events,update of the current knowledge regarding the impact of Tac IPV in different outcomes following kidney,liver,heart,lung,and pancreas tran-splantation to better evaluate its use in clinical practice.

Voriconazole-Induced Periostitis &Enthesopathy in Solid Organ Transplant Patients: Case Reports

Background: Voriconazole is frequently used to treat fungal infections in solid organ transplant patients. Recently, there have been reports suggesting that prolonged voriconazole therapy may lead to periostitis. Aim: Here we present two cases of voriconazole-induced periostitis in solid organ transplant patients. Case Presentation: Voriconazole was given to two transplant patients-one with a liver transplant and the second with a heart transplant, to treat their fungal infections. Both developed voriconazole-induced toxicity. While undergoing voriconazole therapy, they had incapacitating bone pain. The liver transplant patient had to be taken off voriconazole, and the heart transplant patient succumbed to non-voriconazole related causes. Conclusions: Voriconazole therapy in two solid organ transplant patients resulted in periostitis. We provide potential etiologies underlying voriconazole-induced periostitis, including fluoride toxicity, abnormalities in the pulmonary vascular bed leading to the production of downstream inflammatory mediators, and abnormal pharmacokinetics of hepatic drug metabolism. In addition to monitoring blood voriconazole trough levels, we suggest careful assessment for musculoskeletal pain in patients undergoing voriconazole treatment for two months or more, particularly if their daily dosages of voriconazole exceed 500 mg per day. Appropriate workup should include measurement of alkaline phosphatase and fluoride levels, voriconazole trough and bone scan. Overall, early recognition of voriconazole-induced musculoskeletal toxicity is important for better morbidity outcomes.

Chances and risks of sodium-glucose cotransporter 2 inhibitors in solid organ transplantation:A review of literatures

Solid organ transplantation offers life-saving treatment for patients with endorgan dysfunction.Patient survival and quality of life have improved over the past few decades as a result of pharmacological development,expansion of the donor pool,technological advances and standardization of practices related to transplantation.Still,transplantation is associated with cardiovascular complications,of which post-transplant diabetes mellitus(PTDM)is one of the most important.PTDM increases mortality,which is best documented in patients who have received kidney and heart transplants.PTDM results from traditional risk factors seen in patients with type 2 diabetes mellitus,but also from specific posttransplant risk factors such as metabolic side effects of immunosuppressive drugs,post-transplant viral infections and hypomagnesemia.Oral hypoglycaemic agents are the first choice for the treatment of type 2 diabetes mellitus in non-transplanted patients.However,the evidence on the safety and efficacy of oral hypoglycaemic agents in transplant recipients is limited.The favourable risk/benefit ratio,which is suggested by large-scale and long-term studies on new glucoselowering drug classes such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors,makes studies warranted to assess the potential role of these agents in the management of PTDM.

Kidney disease in non-kidney solid organ transplantation

Kidney disease after non-kidney solid organ transplantation(NKSOT)is a common post-transplant complication associated with deleterious outcomes.Kidney disease,both acute kidney injury and chronic kidney disease(CKD)alike,emanates from multifactorial,summative pre-,peri-and post-transplant events.Several factors leading to kidney disease are shared amongst solid organ transplantation in addition to distinct mechanisms unique to individual transplant types.The aim of this review is to summarize the current literature describing kidney disease in NKSOT.We conducted a narrative review of pertinent studies on the subject,limiting our search to full text studies in the English language.Kidney disease after NKSOT is prevalent,particularly in intestinal and lung transplantation.Management strategies in the peri-operative and post-transplant periods including proteinuria management,calcineurin-inhibitor minimization/sparing approaches,and nephrology referral can counteract CKD progression and/or aid in subsequent kidney after solid organ transplantation.Kidney disease after NKSOT is an important consideration in organ allocation practices,ethics of transplantation.Kidney disease after SOT is an incipient condition demanding further inquiry.While some truths have been revealed about this chronic disease,as we have aimed to describe in this review,continued multidisciplinary efforts are needed more than ever to combat this threat to patient and allograft survival.

Solid organ transplantations and COVID-19 disease

Tens of thousands of people worldwide became infected with syndrome coronavirus-2(SARS-CoV-2).Death rate in general population is about 1%-6%,but this rate rises up to 15%in those with comorbidities.Recent publications showed that the clinical progression of this disease in organ recipients is more destructive,with a fatality rate of up to 14%-25%.We aimed to review the effect of pandemic on various transplantation patients.coronavirus disease 2019(COVID-19)has not only interrupted waiting list patients’lives;it has also impacted transplantation strategies,transplant surgeries and broke donation chains.COVID-19 was directly and indirectly accountable for 73%surplus in mortality of this population as compared to wait listed patients in earlier years.The impact of chronic immunosuppression on outcomes of COVID-19 remains unclear but understanding the immunological mechanisms related to the virus is critically important for the lifetime of transplantation and immune suppressed patients.It is hard to endorse changing anti-rejection therapy,as the existing data appraised is not adequate to advise substituting tacrolimus with cyclosporine during severe COVID-19 disease.

Organ donation in China:the major progress and the continuing problem

China has banned harvesting organs from executed prisoners since January 1st, 2015, making voluntary donation the only legitimate venue for organ transplant. It is a critical move to settle all the controversies about China＇s organ transplant process by making a loud and strong statement worldwide that the Chinese government respects human rights and is streamlining its organ transplant process to conform with internationally accepted standards on organ transplantation. This regulation removes one major obstacle of organ transplant in China; however, China still faces the other maior obstacle of critical organ shortage.

Ethical tensions in solid organ transplantation: The price of success

Solid organ transplantation has rapidly developed into the therapy a choice for end-stage organ failure. The expansion of its use has resulted is a large deficiency in organ supply. To address this, the field of organ transplantation has attempted to develop new strategies that would increase the availability of organs for transplant. Some of these strategies include expansion of the donor pool by increasing the number of living donors or using deceased donor organs that may be marginal or ＂expanded＂ The intent is to bring life-saving therapy to individuals in need; however, much of this expansion has been brought forward without clear prospective guidelines. This article focuses on the current disparity between organ supply and demand, and how this has impacted the use of living donors and development of the ＂expanded donor＂ concept.

Brain death and organ transplant legislation: analysis of 969 respondents by classroom questionnaire

BACKGROUND: China has the largest potential market for organ transplants in the world, but it has not yet established brain death and organ transplant laws. We aimed to investigate the attitudes and suggestions of doctors, pharmacists, and civil servants concerning brain death, organ transplantation, and their respective legislation. METHODS: A questionnaire with 10 sections and 44 questions was designed and distributed. The effective questionnaire data were then recorded and checked for descriptive analysis. RESULTS: In 1400 questionnaires distributed, 1063 were responded and 969 of them were valid and analyzed. The respondents showed an incomplete understanding of brain death and organ transplantation laws. Seventy-four percent of the respondents recognized and accepted the standard of brain death. They agreed that legislation should be involved in the removal of organs for transplantation, the future use of organs, and insurance and compensation for the donor for possible health risks induced by organ removal. Of the 969 respondents, 92% considered it necessary to have legislation in brain death and organ transplantation, and 61% thought that it is time to legislate. CONCLUSIONS: Legislation for brain death and organ transplantation is urgent and timely in China. The laws must include the respective rights and obligations of patients, close relatives, and medical institutions. Educating the public about brain death and organ transplantation should also be encouraged in a variety of ways.

Renal manifestations of hepatitis E among immunocompetent and solid organ transplant recipients

Hepatitis E virus(HEV)infections are generally self-limited.Rare cases of hepatitis E induced fulminant liver failure requiring liver transplantation are reported in the literature.Even though HEV infection is generally encountered among developing countries,a recent uptrend is reported in developed countries.Consumption of unprocessed meat and zoonosis are considered to be the likely transmission modalities in developed countries.Renal involvement of HEV generally holds a benign and self-limited course.Although rare cases of cryoglobulinemia are reported in immunocompetent patients,glomerular manifestations of HEV infection are frequently encountered in immunocompromised and solid organ transplant recipients.The spectrum of renal manifestations of HEV infection include prerenal failure,glomerular disorders,tubular and interstitial injury.Kidney biopsy is the gold standard diagnostic test that confirms the pattern of injury.Management predominantly includes conservative approach.Reduction of immunosuppressive medications and ribavirin(for 3-6 mo)is considered among patients with solid organ transplants.Here we review the clinical course,pathogenesis,renal manifestations,and management of HEV among immunocompetent and solid organ transplant recipients.

Research progress of soluble CD83 in organ transplantation

Organ transplantation is considered to be an effective method for the treatment of end-stage organ failure,early malignant tumors and tissue damage.In order to reduce the rejection of the transplanted organ by the host,immunosuppressive drugs should be used for a long time,but the suppression of the host immune system by immunosuppressive drugs can cause serious side effects.Therefore,how to induce the recipient's immune system to have no response to the transplanted organ after transplantation,while still showing a normal immune response to the alien antigen.Induction of immune tolerance to donor organs has long been a focus of research by transplant scientists.Soluble CD83(sCD83)is a glycoprotein with specific immunosuppressive effects.In recent years,there have been more and more reports on the immune tolerance induced by sCD83 in animal experiments,which has shown a broad prospect in the treatment of host immune rejection after organ transplantation and provided an experimental basis for its clinical transformation.