Advancing immunosuppression in liver transplantation: A narrative review

Immunosuppression is essential to ensure recipient and graft survivals after liver transplantation(LT). However, our understanding and management of the immune system remain suboptimal. Current immunosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a significant risk of serious side effects, i.e., among others, de novo cancers, infections, cardiovascular events, renal failure, metabolic syndrome, and late graft fibrosis, with progressive loss of graft function. Pharmacological research, aimed to develop alternative immunosuppressive agents in LT, is behind other solidorgan transplantation subspecialties, and, therefore, the development of new compounds and strategies should get priority in LT. The research trajectories cover mechanisms to induce T-cell exhaustion, to inhibit co-stimulation, to mitigate non-antigen-specific inflammatory response, and, lastly, to minimize the development and action of donor-specific antibodies. Moreover, while cellular modulation techniques are complex, active research is underway to foster the action of T-regulatory cells, to induce tolerogenic dendritic cells, and to promote the function of B-regulatory cells. We herein discuss current lines of research in clinical immunosuppression, particularly focusing on possible applications in the LT setting.

Effects of Rosa roxburghii&edible fungus fermentation broth on immune response and gut microbiota in immunosuppressed mice

With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still exist.In addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor progression.The aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies.Therefore,personalized treatments could be developed to maximize the advantages of immunotherapy.

Pleural empyema with endobronchial mass due to Rhodococcus equi infection after renal transplantation: A case report and review of literature

BACKGROUND Kidney transplantation is the best option for patients with end-stage renal disease.However,the need for lifelong immunosuppression results in renal transplant recipients being susceptible to various infections.Rhodococcus equi(R.equi)is a rare opportunistic pathogen in humans,and there are limited reports of infection with R.equi in post-renal transplant recipients and no uniform standard of treat-ment.This article reports on the diagnosis and treatment of a renal transplant recipient infected with R.equi 21 mo postoperatively and summarizes the charac-teristics of infection with R.equi after renal transplantation,along with a detailed review of the literature.Here,we present the case of a 25-year-old man who was infected with R.equi 21 mo after renal transplantation.Although the clinical features at the time of presentation were not specific,chest computed tomography(CT)showed a large volume of pus in the right thoracic cavity and right middle lung atelectasis,and fiberoptic bronchoscopy showed an endobronchial mass in the right middle and lower lobe orifices.Bacterial culture and metagenomic next-generation sequen-cing sequencing of the pus were suggestive of R.equi infection.The immunosup-pressive drugs were immediately suspended and intravenous vancomycin and azithromycin were administered,along with adequate drainage of the abscess.The endobronchial mass was then resected.After the patient’s clinical symptoms and chest CT presentation resolved,he was switched to intravenous ciprofloxacin and azithromycin,followed by oral ciprofloxacin and azithromycin.The patient was re-hospitalized 2 wk after discharge for recurrence of R.equi infection.He recovered after another round of adequate abscess drainage and intravenous ciprofloxacin and azithromycin.CONCLUSION Infection with R.equi in renal transplant recipients is rare and complex,and the clinical presentation lacks specificity.Elaborate antibiotic therapy is required,and adequate abscess drainage and surgical excision are necessary.Given the recurrent nature of R.equi,patients need to be followed-up closely.

Mechanisms of myeloid-derived suppressor cell-mediated immunosuppression in colorectal cancer and related therapies

Severe immunosuppression is a hallmark of colorectal cancer(CRC).Myeloid-derived suppressor cells(MDSCs),one of the most abundant components of the tumor stroma,play an important role in the invasion,metastasis,and immune escape of CRC.MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells,including T and natural killer cells,as well as by inducing the proliferation of immunosuppressive cells,such as regulatory T cells and tumor-associated macrophages,which,in turn,promote the growth of cancer cells.Thus,MDSCs are key contributors to the emergence of an immunosup-pressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity.In this narrative review,we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment,the current therapeutic approaches and technologies targeting MDSCs,and the therapeutic potential of modulating MDSCs in CRC treatment.This study provides ideas and methods to enhance survival rates in patients with CRC.

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.

Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients

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.

Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression

Colorectal cancer(CRC)remains one of the most commonly diagnosed and deadliest types of cancer worldwide.CRC displays a desmoplastic reaction(DR)that has been inversely associated with poor prognosis;less DR is associated with a better prognosis.This reaction generates excessive connective tissue,in which cancer-associated fibroblasts(CAFs)are critical cells that form a part of the tumor microenvironment.CAFs are directly involved in tumorigenesis through different mechanisms.However,their role in immunosuppression in CRC is not well understood,and the precise role of signal transducers and activators of transcription(STATs)in mediating CAF activity in CRC remains unclear.Among the myriad chemical and biological factors that affect CAFs,different cytokines mediate their function by activating STAT signaling pathways.Thus,the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors.Here,we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

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.

Advancements in autoimmune hepatitis management:Perspectives for future guidelines

The first-line treatment for autoimmune hepatitis involves the use of prednisone or prednisolone either as monotherapy or in combination with azathioprine(AZA).Budesonide has shown promise in inducing a complete biochemical response(CBR)with fewer adverse effects and is considered an optional first-line treatment,particularly for patients without cirrhosis;however,it is worth noting that the design of that study favored budesonide.A recent real-life study revealed higher CBR rates with prednisone when equivalent initial doses were administered.Current guidelines recommend mycophenolate mofetil(MMF)for patients who are intolerant to AZA.It is important to mention that the evidence supporting this recommendation is weak,primarily consisting of case series.Nevertheless,MMF has demonstrated superiority to AZA in the context of renal transplant.Recent comparative studies have shown higher CBR rates,lower therapeutic failure rates,and reduced intolerance in the MMF group.These findings may influence future guidelines,potentially leading to a significant modification in the first-line treatment of autoimmune hepatitis.Until recently,the only alternative to corticosteroids was lifelong maintenance treatment with AZA,which comes with notable risks,such as skin cancer and lymphoma.Prospective trials are essential for a more comprehensive assessment of treatment suspension strategies,whether relying on histological criteria,strict biochemical criteria,or a combination of both.Single-center studies using chloroquine diphosphate have shown promising results in significantly reducing relapse rates compared to placebo.However,these interesting findings have yet to be replicated by other research groups.Additionally,second-line drugs,such as tacrolimus,rituximab,and infliximab,should be subjected to controlled trials for further evaluation.

Dynamically changing antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis:A case report

BACKGROUND Granulomatosis with polyangiitis(GPA)is one of the most prevalent forms of the antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis.GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis.The diagnosis of GPA depends on clinical presentation,serological evidence of a positive ANCA,and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation.Cytoplasmic ANCA(c-ANCA)is positive in 65%-75% of GPA patients,accompanied by proteinase 3(PR3),the main target antigen of c-ANCA,another 5% of GPA patients had negative ANCA.CASE SUMMARY The patient,a 52-year-old male,presented with unexplained nasal congestion,tinnitus,and hearing loss.After a duration of 4 months experiencing these symptoms,the patient subsequently developed fever and headache.The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis,and the ANCA results were negative.The anti-infective therapy proved to be ineffective,but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day.However,after continuous use of methylprednisolone tablets for 3 months,the patient experienced a recurrence of fever accompanied by right-sided migraine,positive c-ANCA and PR3,and increased total protein in cerebrospinal fluid.The and cyclophosphamide 0.8 g monthly,the patient experienced alleviation of fever and headache.Additionally,the ANCA levels became negative and there has been no recurrence.CONCLUSION For GPA patients with negative ANCA,there is a potential for early missed diagnosis.The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.

Colon signet-ring cell carcinoma with chylous ascites caused by immunosuppressants following liver transplantation:A case report

BACKGROUND Chylous ascites is caused by disruption of the lymphatic system,which is characterized by the accumulation of a turbid fluid containing high levels of triglycerides within the abdominal cavity.The two most common causes are cirrhosis and tuberculosis,and colon signer ring cell carcinoma(SRCC)due to the use of immunosuppressants is extremely rare in cirrhotic patients after liver transplantation,making it prone to misdiagnosis and missed diagnosis.CASE SUMMARY A 52-year-old man who underwent liver transplantation and was administered with immunosuppressants for 8 months was admitted with a 3-month history of progressive abdominal distention.Initially,based on lymphoscintigraphy and lymphangiography,lymphatic obstruction was considered,and cystellar chyli decompression with band lysis and external membrane stripping of the lymphatic duct was performed.However,his abdominal distention was persistent without resolution.Abdominal paracentesis revealed allogenic cells in the ascites,and immunohistochemistry analysis revealed adenocarcinoma cells with phenotypic features suggestive of a gastrointestinal origin.Gastrointestinal endoscopy was performed,and biopsy showed atypical signet ring cells in the ileocecal valve.The patient eventually died after a three-month follow-up due to progression of the tumor.CONCLUSION Colon SRCC,caused by immunosuppressants,is an unusual but un-neglected cause of chylous ascites.

Update on the reciprocal interference between immunosuppressive therapy and gut microbiota after kidney transplantation

Gut microbiota is often modified after kidney transplantation.This principally happens in the first period after transplantation.Antibiotics and,most of all,immunosuppressive drugs are the main responsible.The relationship between immunosuppressive drugs and the gut microbiota is bilateral.From one side immunosuppressive drugs modify the gut microbiota,often generating dysbiosis;from the other side microbiota may interfere with the immunosuppressant pharmacokinetics,producing products more or less active with respect to the original drug.These phenomena have influence over the graft outcomes and clinical consequences as rejections,infections,diarrhea may be caused by the dysbiotic condition.Corticosteroids,calcineurin inhibitors such as tacrolimus and cyclosporine,mycophenolate mofetil and mTOR inhibitors are the immunosuppressive drugs whose effect on the gut microbiota is better known.In contrast is well known how the gut microbiota may interfere with glucocorticoids,which may be transformed into androgens.Tacrolimus may be transformed by microbiota into a product called M1 that is 15-fold less active with respect to tacrolimus.The pro-drug mycophenolate mofetil is normally transformed in mycophenolic acid that according the presence or not of microbes producing the enzyme glucuronidase,may be transformed into the inactive product.

Oesophageal Mycosis: Epidemiological and Clinical Aspects and Risk Factors for Occurrence in the Digestive Endoscopy Unit of the Donka National Hospital, Conakry CHU

Introduction: Oesophageal mycosis (OM) is one of the most common opportunistic infections in patients infected with HIV (Human Immunodeficiency Virus). However, this condition is increasingly observed in immunocompetent subjects. The aim of this study was to determine the endoscopic prevalence, clinical characteristics and risk factors for the occurrence of oesophageal mycosis in our department. Patients and Method: This was a prospective cross-sectional study of all patients who underwent oeso-gastroduodenal fibroscopy during the period from 1st January to 31st December 2022, i.e. one year, at the digestive endoscopy unit of the hepato-gastroenterology department of the Donka CHU national hospital in Conakry. All patients found to have oesophageal mycosis by FOGD were included. The endoscopy was performed using appropriate equipment: A Fujinon 4400 video endoscopy column;Three Fujinon EG 590 video gastroscopes;A hoover;Data were collected using a pre-established survey form and analysed using Epi info software version 6.0.4;Pearson’s Chi2 test as a test of independence and the exact 5% threshold ficher test. Results: Out of 1343 upper gastrointestinal endoscopies performed, 107 cases of oesophageal mycosis were found, representing a prevalence of 7.96%. The mean age was 40 years, with a male predominance of 55.42%. The sex ratio M/F was 1.24. The 45 and over age group was the most affected, with a prevalence of 40.43%, followed by the [35 - 45] age group, with a prevalence of 22.43%. Clinical symptoms were dominated by epigastralgia in 74.76% of cases, followed by odynophagia in 37.38% of cases, nausea and vomiting in 28.03% of cases, and pyrosis in 26.16% of cases. Oesophageal mycosis without oesophagitis was the most common endoscopic finding in 70% of cases. The main associated endoscopic lesions were erythemato-erosive and congestive gastropathy in 28.03% of cases, peptic oesophagitis (9.34%) and gastric ulcer (5.60%). The main risk factors found were positive HIV serology in 39.25% of cases, and diabetes in 24.30% of cases, with a statistically significant relationship of 0.02 and 0.01 respectively. Conclusion: Oesophageal mycosis is the most common opportunistic infection in patients with impaired cellular immunity. The prevalence of oesophageal mycosis in our series was 7.96%. This study enabled us to identify the main risk factors for the occurrence of oesophageal mycosis. Our country needs to step up its programme to combat and prevent immunodeficiency diseases, particularly HIV and diabetes.

Immunology demystified: A guide for transplant hepatologists

Liver transplantation has become standard practice for treating end-stage liver disease.The success of the procedure relies on effective immunosuppressive medications to control the host's immune response.Despite the liver's inherent capacity to foster tolerance,the early post-transplant period is marked by significant immune reactivity.To ensure favorable outcomes,it is imperative to identify and manage various rejection types,encompassing T-cell-mediated,antibody-mediated,and chronic rejection.However,the approach to prescribing immunosuppressants relies heavily on clinical judgment rather than evidencebased criteria.Given that the majority of patients will require lifelong immunosuppression as the mechanisms underlying operational tolerance are still being investigated,healthcare providers must possess an understanding of immune responses,rejection mechanisms,and the pathways targeted by immunosuppressive drugs.This knowledge enables customization of treatments and improved patient care,even though a consensus on an optimal immunosuppressive regimen remains elusive.

Predicting outcomes after kidney transplantation: Can Pareto’s rules help us to do so?

Kidney transplantation is the best option for kidney replacement therapy,even considering that most of the times the grafts do not survive as long as their recipients.In the Khalil et al's experience,published in this issue of the Journal,they analyze their second kidney graft survival and describe those significant predictors of early loss.This editorial comments on the results and put in perspective that most of the times,long-term graft survival could be inadvertently jeopardized if the immunosuppressive therapy is reduced or withdrawn for any reason,and that it could happen frequently if the transplant physician intends to innovate with the clinical care without proper evidence-based data.

Management strategies for common viral infections in pediatric renal transplant recipients

Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes.Hence,prevention,early detection,and prompt treatment of such infections are of paramount importance.Among all viral infections,herpes viruses(herpes simplex virus,varicella zoster virus,Epstein-Barr virus,cytomegalovirus),hepatitis B and C viruses,BK polyomavirus,and respiratory viruses(respiratory syncytial virus,parainfluenza virus,influenza virus and adenovirus)are common in kidney transplant recipients.These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome.Recent advances in technology and antiviral therapy have improved management strategies in screening,monitoring,adoption of prophylactic or preemptive therapy and precise treatment in the immunocompromised host,with significant impact on the outcome.This review discusses the etiology,screening and monitoring,diagnosis,prevention,and treatment of common viral infections in pediatric renal transplant recipients.

Kaposi Sarcoma after Kidney Transplant: A Clinical Case Report

Kaposi sarcoma is a neoplasm caused by human herpesvirus 8 (HHV8) that most commonly affects immunosuppressed patients. The skin is the most affected area, but other sites can be involved such as the lung, digestive tract and lymph nodes. The classical presentation involves a violaceous skin lesion that can be small or hidden, leading to a delay in diagnosis. We report a clinical case of a kidney transplant patient, who presented, 14 months after kidney transplant, with unilateral edema of the inferior member and cutaneous rash misdiagnosed and taken initially for erysipelas. The diagnosis of Kaposi’s sarcoma was retained, on a lymph node biopsy of an inguinal adenopathy. The evolution was marked by a local and general improvement after systemic chemotherapy, reducing Tacrolimus and discontinuation of Mycophenolate mofetil. Graft function remained stable during the follow-up.

Return to Dialysis after Kidney Graft Failure

Introduction: The transition period from renal transplantation to dialysis is associated with high morbidity and mortality. The aim of this study is to describe the clinical and paraclinical characteristics, therapeutic management and evolutionary profile of patients returning to dialysis after kidney graft failure. Material and Methods: This was a retrospective, descriptive study conducted in the Nephrology-Dialysis-Renal Transplant Department at university hospital IbnSina between January 1998 and December 2021. We included all renal transplant recipients who had experienced kidney graft dysfunction and returned to dialysis. Patients with a follow-up after return to dialysis of less than 1 year were excluded. Results: Among 166 renal transplant recipients, 20 returned to dialysis after a median renal graft life of 85.5 months [42 - 186], corresponding to a prevalence of 12%. The mean age of our patients was 38.7 ± 11.9 years, with a M/F sex ratio of 2.3. Dialysis was initiated urgently in 10 patients (50%). Hemodialysis was the most commonly used modality (75%). Central venous catheterization was used in 35% of cases, including tunneled catheters. General condition is impaired in all patients, with persistent hypertension in 70% of cases. Mean uremia was 2.35 ± 0.8 g/l, mean creatinine 116 ± 48.3 mg/l, giving a mean GFR of 5.1 ± 2.2 ml/min. Mean albuminemia was 32.9 ± 6 g/l and mean hemoglobinemia 8.6 ± 1.9 g/dl. During the first year of follow-up, none of the patients died. However, 13 patients required hospitalization, with a mean length of stay of 15 days. Eight patients were hospitalized for infections and 5 for renal graft intolerance syndrome. After a mean follow-up of 22 months, 6 patients were detransplanted following graft necrosis. Conclusion: Return to dialysis after RT is fraught with a high rate of complications. The management of these patients must be optimized to improve their vital prognosis and quality of life.

Clinical Exploration of Immunosuppressants Combined with Abiraterone in the Treatment of Metastatic Castration-Resistant Prostate Cancer

Prostate cancer is a malignant tumor with a high incidence in elderly men.In recent years,with the improvement of people’s living standards and the advancement of detection technology,the incidence of prostate cancer has been increasing year by year.Castration-resistant prostate cancer(CRPC)is a highly challenging type of advanced prostate cancer treatment,which clinically shows resistance to hormonal deprivation therapy.The overall treatment efficacy of CRPC is currently poor and further relevant therapeutic studies are needed to improve patient survival and quality of life.Immunosuppressants can play a role in combating the immune system of tumors,and abiraterone has also achieved remarkable results in prostate cancer treatment.This study will investigate the possible clinical effects and safety of immunosuppressants combined with abiraterone in the treatment of metastatic CRPC.The population-based study will provide clinicians with more effective treatment options,as well as enhance the understanding of novel combination therapy strategies to be implemented in the future for such patients.