Incidence and risk factors of de novo hepatitis E virus infection after receiving liver transplantation.

Organ transplant recipients with hepatitis E virus (HEV) infection bears high risk to develop chronic hepatitis, which is generally associated with immunosuppressive therapies. This study aimed to identify the incidence and predictors of de novo HEV infection in patients after receiving transplantation. We performed a large retrospective study to investigate the prevalence of anti-HEV at baseline, incidence of de novo HEV infection after transplantation, and the risk factors of HEV infection among patients with liver transplant in China. A total of 407 liver transplant recipients were examined for the presence of anti-HEV immunoglobulin G, IgM antibodies, and HEV RNA in serum. Basal indexes in individuals with evidence of post-transplant HEV infection were compared with those without evidence of that, and risk factors associated with HEV infection were assessed. The prevalence of anti-HEV at pretransplant in liver transplant recipients was 25.8% (105/407). Serum-negative conversion occurred in 34 (32.38%) of 105 liver transplant patients. Sixty-five out of 302 patients had de novo HEV infection after transplantation, with a cumulative incidence of 42.74% during follow-up. After transplantation, HEV infection was associated with liver failure (p = 0.012), hypoproteinemia (p = 0.030) and higher level of r-glutamyl transferase (GGT) (p = 0.022) before transplantation. Graft rejection (OR = 0.075; p = 0.045) was negatively associated with serum-negative conversion in patients who had positive anti-HEV antibody before transplantation. The incidence of de novo HEV infection after transplantation were higher in China. Liver failure, hypoproteinemia, and GGT elevation may be associated with HEV infection after liver transplantation. This study suggests that prevention and control of HEV infection after liver transplantation should be paid attention in patients bearing these risk factors.

The impact of high intensity training and sports on recipients of solid organ transplants: a narrative review.

Objectives: High intensity exercise in individuals post solid organ transplant (SOT) remains a largely understudied phenomenon, with potential risks and benefits. Additionally, the optimal training protocols are still unclear. This narrative review aimed to explore the impact of high-intensity exercise training and strenuous sports on solid organ transplant recipients (SOTRs). Methods: We conducted a narrative review of intervention studies of any design that included high-intensity exercise training and cross-sectional studies of strenuous sports and activities. Additionally, we reviewed individual reports documenting post-SOT performance at highly competitive or physiological levels. We used MEDLINE to search for relevant articles followed by a manual search for additional articles. Data were extracted and results were summarized. Results: High-intensity and strenuous exercise appears to be safe among stable SOTRs. High-intensity protocols consistently demonstrated improvements in VO2peak and a reduction in coronary artery disease prevalence, though findings related to body composition, health-related quality of life outcomes, and cardiovascular exercise variables were inconsistent. Pre-transplant athletes showcase notable achievements and physiological adaptations post-transplantation, highlighting the capacity for athletic performance among this population. However, caution is warranted in interpreting the findings from these studies due to limitations in generalizability and other methodological limitations. Conclusion: As evidenced by current literature, high intensity exercise emerges as a promising exercise method for safely improving various physiological parameters, and reducing the prevalence of coronary heart disease in SOTRs. It can induce similar or greater effects to moderate intensity exercise, however follow-up studies indicate low retention. Further research of higher methodological rigor is warranted in this field to advance understanding, and to guide evidence-based practice.

Effect of CYP3A5*3, ABCC2 C-24T, and ABCC2 C3972T Genetic Polymorphisms on Direct Cost of Kidney Transplant Recipients.

Introduction Genetic variations can influence how kidney transplant recipients (KTRs) respond to immunosuppressive drugs. However, limited resources necessitate a cost-benefit analysis of pharmacogenetic testing to determine its role in routine practice. This study investigated the cost-effectiveness of three genetic polymorphisms (CYP3A5*3, ABCC2 -24C>T, and ABCC2 3972C>T) in KTRs. Methods This was a multicenter, prospective observational cohort study that included patients on tacrolimus-mycophenolate-prednisolone treatment. Ethnically diverse adult KTRs who had undergone kidney transplantation between 2020 and 2021 and consented were enrolled in the study. Deoxyribonucleic acid (DNA) was extracted from the collected blood samples using a commercially available kit. CYP3A5*3, ABCC2 -24C>T, and ABCC2 3972C>T single nucleotide polymorphisms (SNPs) were determined by polymerase chain reaction (PCR). Results Data was analyzed from 39 KTRs with an average age of 32.2 ± 7.0 years. The median annual healthcare cost per patient was MYR 52,700 (laboratory tests and immunosuppressants being the highest expenses). Notably, the annual cost was significantly higher in patients with the CYP3A5*3 variant compared to the wildtype (p < 0.001). Furthermore, an incremental cost-effectiveness analysis revealed that carriers of the CYP3A5*1 wildtype allele, the ABCC2 -24C>T T variant allele, and the ABCC2 3972C>T T variant allele were associated with a more cost-effective approach to kidney transplantation management, potentially reducing the risk of graft rejection and acute tubular necrosis (ATN). Conclusion While these findings suggest potential cost benefits for specific genotypes, further research with larger and more diverse patient populations is necessary to definitively establish the role of pharmacogenetic testing in optimizing cost-effectiveness for KTRs.

Social Determinants of Health Factors and Self-Management of Care in Kidney Transplant Recipients: A Descriptive Cross-Sectional Study.

Managing post-transplant care poses challenges for kidney transplant recipients, often due to food affordability and the ability to participate in physical activity. This study explored recipients' self-management of care and the influence of social determinants of health on physical activity and diet. A single-center, cross-sectional study recruited 26 participants via My Chart (an Integrated Healthcare Information System patient portal) to complete an 86-question survey. Participants had a mean age of 61 years, and 85% held an associate degree or higher. Body mass index correlated negatively with avoiding high-calorie foods; age and education correlated positively with physical activity. Kidney transplant recipients exhibited limited exercise and frequent high-calorie food consumption. Targeted interventions, particularly promoting regular physical activity, are crucial for improving post-transplant care.

Outcomes of COVID-19 in 24 hospitalized liver transplant recipients: an observational study.

BACKGROUND: Although liver transplant (LT) recipients are considered a population at risk of severe features of coronavirus disease 2019 (COVID-19), data in this regard are scarce and controversial. In this study, we reported the outcome of 24 cases of LT recipients who were hospitalized due to COVID-19 and investigated the role-playing factors in the severity of the disease. METHODS: In this single-center, analytic case-series study, eligible patients were among LT recipients who were hospitalized due to the diagnosis of COVID-19 based on positive results of polymerase chain reaction. Participants were categorized as severe COVID-19 if they were admitted to the intensive care unit, experienced respiratory failure demanding mechanical ventilation, or eventually died. Demographic and clinical data, COVID-19 symptoms and specific treatments, laboratory biomarkers, and immunosuppressive regimens and their alteration during the admission were recorded. Analysis was done using SPSS software. RESULTS: Twenty-four hospitalized LT patients were included, of which nine had severe and fifteen had non-severe COVID-19. Out of 9 patients with severe COVID-19, four sadly died. The analysis and comparison between the two groups revealed longer hospital stays (P = 0.02), lower lymphocyte counts (P = 0.002), and higher levels of C-reactive protein (CRP) (P = 0.006) in patients with severe COVID-19. Patients with non-severe COVID-19 had higher doses of tacrolimus and mycophenolate in their baseline immunosuppressive regimen (both P = 0.02). CONCLUSION: Lymphopenia and high CRP levels are associated with more severe forms of COVID-19 in LT patients. Mycophenolate may have protective properties against severe COVID-19. The role of severity indicators in LT patients with COVID-19 needs to be systematically recognized.

Extensive thigh pyomyositis secondary to cystic fistulae due to anaerobic-bacterial infection in a kidney transplant recipient.

BACKGROUND: Managing infectious complications after kidney transplantation (KT) remains a major challenge. Infections are the leading non-cardiovascular cause of death among kidney transplant recipients (KTr). The urinary tract is particularly vulnerable to infections in this group, leading to high levels of morbidity and mortality, as well as significant economic costs. CASE PRESENTATION: This case report presents the first documented instance of extensive thigh pyomyositis resulting from cystic fistulae in an 84-year-old KTr. The patient was referred to our hospital with acute onset fever, pain in the inner thighs and pyuria. A CT scan revealed bilateral pyomyositis of the thighs, characterized by multiple abscesses in the adductor muscles and hydroaerobic levels. Additionally, cystic fistulae complicated by pubic symphysis osteitis were identified. CONCLUSION: In KTr, lower limb pyomyositis resulting from a urinary tract infection is an extremely rare and significantly worsens the overall prognosis for these patients.

mRNA-based COVID-19 vaccination of lung transplant recipients with prior SARS-CoV-2 infection induces durable SARS-CoV-2-specific antibodies and T cells.

Lung transplant recipients (LTRs) are particularly at risk of developing severe coronavirus disease-2019 (COVID-19), but are also difficult to protect by vaccination due to their immunocompromised state. Here, we investigated the immunogenicity of mRNA-based COVID-19 vaccines in LTRs who had a prior natural SARS-CoV-2 infection. At a median of 184 days after SARS-CoV-2 infection, LTRs were vaccinated twice with the mRNA-1273 COVID-19 vaccine, with a 28-day interval. Blood samples were obtained pre-vaccination, 28 days after the first dose, and 28 days and 6 months after the second dose. Spike (S-) and nucleocapsid (N-) specific antibodies were measured, as well as neutralization of the ancestral and Omicron BA.5 variant. S-specific T cell responses were evaluated using IFN-γ ELISpot，IGRA, and activation markers by flow cytometry. Phenotyping of T cells was performed by using high-resolution spectral flow cytometry. Most LTRs with prior infection had detectable S-specific antibodies and T cells at baseline. After the first vaccination, S-specific antibody levels increased significantly; an additional increase was observed after the second vaccination. N-specific antibodies decreased during the study period, indicative of the fact that no further breakthrough infections occurred. An increase in IFN-γ producing T cells was observed after the first vaccination, but no additional boost could be detected after the second vaccination. Antibody levels and virus-specific T cell responses remained significantly higher compared to pre-vaccination levels at 6 months post-vaccination, indicating an additive and durable effect of vaccination after infection in LTRs. Neutralizing antibodies were detected against the ancestral strain and retained cross-reactivity with Omicron BA.5, albeit at lower levels. Moreover, the quantity and phenotype of SARS-CoV-2 spike-specific T cells were similar in LTRs compared to controls with hybrid immunity. In conclusion, mRNA-based COVID-19 vaccines are immunogenic in LTRs with prior immunity, and antibody and T cell responses are durable up to 6 months post-vaccination.

Optimizing the dosing regimen of roxadustat in kidney transplant recipients with early post-transplant anemia.

INTRODUCTION: Roxadustat, an oral inhibitor of hypoxia-inducible factor prolyl hydroxylase domain enzymes, has been approved for the treatment of renal anemia. However, there is a lack of study on its pharmacokinetics in kidney transplant recipients (KTRs) with early posttransplant anemia (PTA). Therefore, the aim of this study is to elucidate the pharmacokinetic characteristics of roxadustat in KTRs with early PTA and optimize the dosing regimen. METHODS: A population pharmacokinetic (PopPK) analysis was performed based on 72-hour full concentration-time profiles collected from 52 Chinese KTRs. Covariates influencing exposure were assessed using stepwise covariate modelling. Monte Carlo simulations were conducted to recommend the dosing regimen for patients with different levels of covariates. RESULTS: PopPK analysis showed that the concentration-time data can be fully described by a two-compartment model. Body weight (BW) and direct bilirubin (DBIL) levels significant affected the apparent clearance of roxadustat. Based on the established model and the estimated exposures of roxadustat by Monte Carlo simulations, a recommended dosing regimen for KTRs with early PTA at varying BW and DBIL levels were developed. Roxadustat at 100 mg three times weekly were suitable for the majority of KTRs with a DBIL level around 3 µmol/L and BW between 50 and 75 kg. The required dose may need to be increased with higher BW and lower DBIL levels, while decreased with lower BW and higher DBIL levels. CONCLUSIONS: It was the first PopPK analysis of roxadustat in KTRs with early PTA, which provide a research basis for optimizing the dosing regimen.

Risk and Reward: Nationwide Analysis of Cardiac Transplant Center Variation in Organ Travel Distance and the Effects on Outcomes.

BACKGROUND: The 2018 UNOS allocation policy change deprioritized geographic boundaries to organ distribution, and the effects of this change have been widespread. The aim of this investigation was to analyze changes in donor transplant center distance for organ travel and corresponding outcomes before and after the allocation policy change. METHODS: The UNOS database was utilized to identify all adult patients waitlisted for heart transplants from 2016 to 2021. Transplant centers were grouped by average donor heart travel distance based on whether they received more or less than 50% of organs from >250 miles away. Descriptive statistics were provided for waitlisted and transplanted patients. Regression analyses modeled waitlist mortality, incidence of transplant, overall survival, and graft survival. RESULTS: Centers with a longer average travel distance had a higher mean annual transplant volume with a reduction in total days on a waitlist (86.6 vs. 149.2 days), an increased cold ischemic time (3.6 vs. 3.2 h), with no significant difference in post-transplant overall survival or graft survival. CONCLUSIONS: The benefits of reducing waitlist time while preserving post-transplant outcomes extend broadly. The trends observed in this investigation will be useful as we revise organ transplant policy in the era of new organ procurement and preservation techniques.

Cutaneous squamous cell carcinoma in solid organ transplant recipients: Current therapeutic and screening strategies.

Solid organ transplant recipients (SOTRs) are particularly prone to developing malignancies, often manifesting multiple tumors and tumors with a heightened susceptibility to metastasis, resulting in much lower survival rates when compared to the general population. Among these, cutaneous squamous cell carcinoma (CSCC) respresent a major challenge in terms of morbidity and mortality following organ transplantation. The management of post-transplant CSCC requires expertise from various disciplines, including dermatology, maxillofacial surgery, transplant medicine, radiation oncology, and medical oncology. Furthermore, the unique behaviors and prevalence of tumors in SOTRs necessitate tailored pathways for screening and treatment, distinct from those designed for immunocompetent patients. Despite the proven efficacy of immune checkpoint inhibitors (ICIs) in several cancers, SOTRs have often been systematically excluded from clinical trials due to concerns about potential allograft rejection and loss. Consequently, most data on the safety and efficacy of ICIs in SOTRs are derived from case series and reports. Given the significant risks involved, alternative therapeutic options should be thoroughly discussed with patients before considering ICI therapy. This literature review aims to provide an overview of CSCC in SOTRs, with a specific emphasis on therapeutic and screening strategies, particularly highlighting immunotherapy.

Association of Non-Standardized MELD Score Exceptions with Waitlist Mortality in Adult Liver Transplant Candidates.

In the US liver allocation system, non-standardized MELD exceptions increase the waitlist priority of candidates whose MELD scores are felt to underestimate their true medical urgency. We determined whether NSEs accurately depict pre-transplant mortality risk by performing mixed-effects Cox proportional hazards models and estimating concordance indices. We also studied the change in frequency of NSEs after the National Liver Review Board's (NLRB) implementation in May 2019. Between June 2016 and April 2022, 60,322 adult candidates were listed, of which 10,280 (17.0%) received an NSE at least once. The mean allocation MELD was 23.9, an increase of 12.0 points from the mean laboratory MELD of 11.9 (p < 0.001). A one-point increase in allocation MELD score due to an NSE was associated with, on average, a 2% reduction in hazard of pre-transplant death (cause-specific HR 0.98, 95% CI [0.96, 1.00], p = 0.02) compared to those with the same laboratory MELD. Laboratory MELD was more accurate than allocation MELD with NSEs in rank-ordering candidates (c-index 0.889 vs 0.857). The proportion of candidates with NSEs decreased significantly after the NLRB from 21.5% to 12.8% (p < 0.001). NSEs substantially increase the waitlist priority of candidates with objectively low medical urgency.

Hepatitis a vaccine immunogenicity and boostability in adults receiving immunosuppressive therapy and adults living with HIV: a prospective single-Centre cohort study.

INTRODUCTION: Hepatitis A (hepA) vaccination is highly immunogenic in healthy individuals, however there is uncertainty about the immunogenicity in immunocompromised populations (ICPs). METHODS: In this prospective cohort study, people living with HIV (PLWH), patients on immunosuppressive mono- and combination therapy, and controls received two hepA vaccine doses at months 0 and 6-12, or three combined hepA/B vaccine doses at months 0, 1 and 6-12. Antibody levels were measured before and at different time-points post-vaccination (T2, 6, 8, 12 months). The primary endpoint was the seroconversion rate (SCR) at T8, defined as hepA antibodies ≥20 mIU/ml. To assess boostability, an additional vaccine dose was administered 1-5 years after T12 in those with antibodies < 50 mIU/ml, with antibody measurements before and seven days after the booster dose. RESULTS: We included 150 participants. At T2 SCRs ranged between 35-58% in ICPs versus 94% in controls. Among PLWH, patients on monotherapy, combination therapy and controls SCRs at T8 were 33/34 (97%), 32/34 (94%), 25/30 (83%) and 28/28 (100%) respectively. The booster dose resulted in 71% additional seroconversion (17/24), with only patients using combination therapy not responding. CONCLUSIONS: HepA vaccination is highly immunogenic in virologically suppressed PLWH and patients on immunosuppressive monotherapy, with SCRs after the complete hepA vaccination schedule similar to controls and adequate booster responses in case of waning immunity. However, patients using immunosuppressive combination therapy as well as all ICPs who did not receive the complete hepA vaccination schedule, are at risk of non-response to vaccination and post-vaccination antibody measurements are recommended.

Radiofrequency Echographic Multi Spectrometry (REMS) Technology for Bone Health Status Evaluation in Kidney Transplant Recipients.

Background: A significant loss in bone density and strength occurs during the post-renal-transplant period with higher susceptibility to fracture. The study aims to compare the performance of the Radiofrequency Echographic Multi Spectrometry (REMS) in the bone mineral density assessment with the conventional dual-energy X-ray absorptiometry (DXA) in a cohort of kidney transplant recipients (KTR). Methods: A cohort of 40 patients underwent both DXA and REMS examinations on the lumbar spine and/or proximal femur. The paired t-test was used to compare DXA and REMS measurements; the chi-square test was used to compare the prevalence of osteoporosis/osteopenia. The agreement between the two techniques was assessed through Spearman's correlation. Results: As expected, most KTR patients were osteopenic or osteoporotic with both REMS and DXA (86.5% and 81% for the femur; 88% and 65% for the lumbar spine p < 0.05). A modest correlation (r = 0.4, p < 0.01) was observed at the lumbar spine between the T-score measured by REMS and DXA. A strong correlation was defined between REMS and DXA in the femoral region (r = 0.7, p < 0.0001). Conclusions: The study demonstrates the exchangeability of the two techniques on the proximal femur in KTR and a higher diagnostic accuracy of REMS at the spine level than DXA.

Investigation of Depression and Post-Traumatic Growth in Renal Transplant Recipients via Self-Assessment.

Objective: In this study, we aimed to determine post-traumatic growth and depression levels in renal transplant recipients and the relationship between these two variables. Design and Methods: The study was conducted with a descriptive, cross-sectional, and correlational design. The data for the study were collected at the organ transplant unit of a research and training hospital located in the west of Turkey. The sample of the study included 122 kidney transplant recipients (n = 122). A Sociodemographic Information Form, the Post-Traumatic Growth (PTG) Inventory, and the Beck Depression Inventory (BDI) were employed to collect data. In the analyses of the data, descriptive statistics, ANOVA, an independent-samples t-test, post hoc tests, and Pearson correlation tests were used. Results: As the ages of the renal transplant recipients increased, their depression scores decreased, while their PTG scores increased. Higher depression levels were identified in the female participants compared to the male participants and in those with a low income compared to other income groups. The lowest PTG levels were found in the recipients who received their kidney transplants from third-degree relatives. Age, gender, economic status, and time of transplant were predictors of depression. The identity of the donor was the most significant predictor of PTG (62% explanation rate). A strong and inverse correlation was found between depression and PTG (p < 0.05). Conclusions: Post-traumatic growth was found to decrease depression. However, while poor economic status led to depression, high economic status did not lead to a significant change in PTG. As education levels increased, PTG decreased, but education status did not have any significant effect on depression. On the other hand, there was a negative correlation between PTG and depression. The results obtained in this study are valuable and important in terms of understanding depression better and determining PTG as a significant factor that could alleviate it.

Impact of bisphosphonate treatment on bone mineral density after kidney transplant.

BACKGROUND: Mineral bone disease is associated with chronic kidney disease and persists after kidney transplantation. Immunosuppressive treatment contributes to the pathogenesis of this disease. Bisphosphonate treatments have shown positive but indefinite results. AIM: To evaluate the effectiveness and safety of bisphosphonate treatment on post kidney transplantation bone mineral density (BMD). METHODS: We included kidney transplant recipients (KTRs) whose BMD was measured after the operation but before the initiation of treatment and their BMD was measured at least one year later. We also evaluated the BMD of KTRs using two valid measurements after transplantation who received no treatment (control group). RESULTS: Out of 254 KTRs, 62 (39 men) were included in the study. Bisphosphonates were initiated in 35 KTRs in total (20 men), 1.1 ± 2.4 years after operation and for a period of 3.9 ± 2.3 years while 27 (19 men) received no treatment. BMD improved significantly in KTRs who received bisphosphonate treatments (from -2.29 ± 1.07 to -1.66 ± 1.09, P < 0.0001). The control group showed a non-significant decrease in BMD after 4.2 ± 1.4 years of follow-up after surgery. Kidney function was not affected by bisphosphonate treatment. In KTRs with established osteoporosis, active treatment had a similar and significant effect on those with osteopenia or normal bone mass. CONCLUSION: In this retrospective study of KTRs receiving bisphosphonate treatment, we showed that active treatment is effective in preventing bone loss irrespective of baseline BMD.

Epidemiology of Campylobacter Species Infection in Kidney Transplant Recipients: A Retrospective Multicentric Case-Control Study in France.

Background: Campylobacteriosis in kidney transplant recipients (KTRs) is the most common identified bacterial cause of diarrhea. Risk factors in KTRs are unknown. Methods: A 10-year multicentric, retrospective 1:1 case-control study was performed in France between 2010 and 2020. The main aim was to identify factors associated with Campylobacter-related infection in KTRs. The KTRs with a functional graft and campylobacteriosis (positive stool culture and/or blood culture and/or positive nucleic amplification test) and their controls matched on transplantation date within the same center were included. Results: We identified 326 patients with campylobacteriosis. The estimated incidence rate of campylobacteriosis was 2.3/1000 patient-years. The infection occurred at a median of 2.4 years posttransplantation. The independent risk factors for campylobacteriosis were use of corticosteroids as maintenance regimen (75.8% vs 66%; P < .001), acute rejection (8.9% vs 4%; P = .048), low lymphocyte count (0.96 vs 1.4 giga/liter (G/L); P < .001), and low basal estimated glomerular filtration rate (eGFR) (44.2 vs 57.5 mL/minute/1.73 m2; P < .001). A fluoroquinolone was initiated in 64 (21.4%) patients, with 51.1% of antimicrobial resistance, whereas almost all strains were erythromycin sensitive. Conclusions: Campylobacteriosis has a higher incidence in the 2 first years of transplantation. The factors independently associated with campylobacteriosis are corticosteroids as maintenance immunosuppressive regimen, low lymphocyte counts, low eGFR, and a history of acute rejection. Due to high antimicrobial resistance with fluoroquinolone, the first line of treatment should be azithromycin.

A Prospective Clinical Study Investigating the Relationship between Periodontal Disease and the Progression of Chronic Kidney Disease in Renal Transplant Recipients.

Background: Periodontal disease and chronic kidney disease (CKD) are both prevalent conditions with significant implications for public health. This prospective clinical study aimed to explore the potential relationship between periodontal disease and the progression of CKD in renal transplant recipients. Materials and Methods: A total of 150 renal transplant recipients with varying degrees of periodontal disease were enrolled in this study. Baseline periodontal assessments, including probing depth, clinical attachment loss, and bleeding on probing, were conducted. The estimated glomerular filtration rate (eGFR) was measured at baseline and followed up at regular intervals over 24 months. Participants were divided into groups based on the severity of periodontal disease for comparative analysis. Results: At baseline, the mean eGFR was 60.5 ± 10.2 mL/min/1.73 m2 in the mild periodontal disease group, 58.3 ± 9.8 mL/min/1.73 m2 in the moderate periodontal disease group, and 55.7 ± 8.5 mL/min/1.73 m2 in the severe periodontal disease group. Over the 24-month follow-up period, participants with severe periodontal disease experienced a significant decline in eGFR compared to those with mild or moderate periodontal disease (P < 0.05). In addition, individuals with severe periodontal disease exhibited a higher incidence of CKD progression, defined as a decline in eGFR greater than 10% from baseline. Conclusion: This prospective clinical study suggests a potential association between severe periodontal disease and the progression of CKD in renal transplant recipients.

Continuous Insulin Therapy to Prevent Post-Transplant Diabetes Mellitus: A Randomized Controlled Trial.

Rationale & Objectives: Hyperglycemia is frequently observed early after transplantation and associated with development of post-transplant diabetes mellitus (PTDM). Here, we assessed continuous subcutaneous insulin infusion (CSII) targeting afternoon hyperglycemia. Study Design: Open-label randomized parallel 3-arm design. Settings & Participants: In total, 85 kidney transplant recipients without previous diabetes diagnosis were randomized to postoperative CSII therapy, basal insulin, or control. Interventions: Insulin was to be initiated at afternoon capillary blood glucose level of ≥140 mg/dL (7.8 mmol/L; CSII and basal insulin) or fasting plasma glucose level of ≥200 mg/dL (11.1 mmol/L; control). Outcomes: Hemoglobin A1c (HbA1c) levels at 3 months post-transplant (primary endpoint). PTDM assessed using oral glucose tolerance test at 12 and 24 months. Results: CSII therapy lasted until median day 18 and maximum day 88. The median HbA1c value at month 3 was 5.6% (38 mmol/mol) in the CSII group versus 5.7% (39 mmol/mol) in the control group (P = 0.70) and 5.4% (36 mmol/mol) in the basal insulin group (P = 0.02). At months 12 and 24, the odds for PTDM were similar compared with the control group (odds ratios [95% confidence intervals], 0.80 [0.18-3.49] and 0.71 [0.15-3.16], respectively) and the basal insulin group (0.96 [0.18-5.68] and 1.51 [0.24-12.84], respectively). Mild hypoglycemia events occurred in the CSII and the basal insulin groups. Limitations: This study is limited by outdated insulin pump technology, frequent discontinuations of CSII, a complex protocol, and concerns regarding reliability of HbA1c measurements. Conclusions: CSII therapy was not superior at reducing HbA1c levels at month 3 or PTDM prevalence at months 12 and 24 compared with the control or basal insulin group.

Vaccination with Tozimameran Induces T-Cell Activation, but Not Senescent or Exhaustive Alterations, in Kidney Transplant Recipients.

BACKGROUND: Multiple vaccinations have potential inimical effects on the immune system aging process. We examined whether response to SARS-CoV-2 vaccination with Tozinameran is associated with immunosenescence and immunoexhaustion in kidney transplant recipients (KTRs). METHODS: In this prospective observational study, we observed 39 adult kidney transplant recipients (KTRs) who had no pre-existing anti-SARS-CoV-2 antibodies and were on stable immunosuppression. CD4+ and CD8+ T-cell subpopulations [comprising CD45RA+CCR7+ (naïve), CD45RA-CCR7+ (T-central memory, TCM), CD45RA-CCR7- (T-effector memory, TEM) and CD45RA+CCR7- (T-effector memory re-expressing CD45RA, TEMRA, senescent), CD28- (senescent) and PD1+ (exhausted)] were evaluated at 2 time points: T1 (48 h prior to the 3rd), and T2 (3 weeks following the 3rd Tozinameran dose administration). At each time point, patients were separated into Humoral and/or Cellular Responders and Non-Responders. RESULTS: From T1 to T2, CD4+TCM and CD8+TEM were increased, while naïve CD4+ and CD8+ proportions were reduced in the whole cohort of patients, more prominently among responders. At T2, responders compared to non-responders had higher CD8+CD28+ [227.15 (166) vs. 131.44 (121) cells/µL, p: 0.036], lower CD4+CD28- T-lymphocyte numbers [59.65 (66) cells/µL vs. 161.19 (92) cells/µL, p: 0.026] and percentages [6.1 (5.5)% vs. 20.7 (25)%, p: 0.04]. CONCLUSION: In KTRs, response to vaccination is not associated with an expansion of senescent and exhausted T-cell concentrations, but rather with a switch from naïve to differentiated-activated T-cell forms.

Immune Control of Human Cytomegalovirus (HCMV) Infection in HCMV-Seropositive Solid Organ Transplant Recipients: The Predictive Role of Different Immunological Assays.

Human cytomegalovirus (HCMV) infection remains a major complication for solid organ transplant recipients (SOTRs). The aim of this study was to evaluate the role of HCMV-specific T cell immunity measured at the time of the HCMV-DNA peak in predicting the spontaneous clearance of infection. The performance of cytokine flow cytometry using infected dendritic cells (CFC-iDC), infected cell lysate (CFC-iCL) and pp65 peptide pool (CFC-pp65 pool) as stimuli, as well as ELISPOT assays using infected cell lysate (ELISPOT-iCL) and the pp65 peptide pool (ELISPOT-pp65 pool), was analysed. Among the 40 SOTRs enrolled, 16 patients (40%) required antiviral treatment for an HCMV infection (Non-Controllers), while the others spontaneously cleared the infection (Controllers). At the HCMV-DNA peak, the number of HCMV-specific CD4+ T cells detected by the CFC-iDC, CFC-iCL and CFC-pp65 pool assays in Controllers was higher than that detected in Non-Controllers, while no difference was observed in terms of HCMV-specific CD8+ T cell response. The same trend was observed when the HCMV-specific T cell response was measured by ELISPOT-iCL and ELISPOT-pp65 pool. We observed that the CD4+ CFC-pp65 pool assay was the best predictor of self-resolving HCMV infection at the time of the HCVM-DNA peak. The CFC-pp65 pool assay is able to discriminate between CD4+ and CD8+ T cell responses and could be used in daily clinical practice.