Early Post-transplant Period Research Articles

P-2274. Incidence and Microbiology of Postoperative Pleural Space Infections among Lung Transplant Recipients

Abstract Background Pleural space infections (PSI) represent a known complication of lung transplantation (LT) in the early posttransplant period. Within the historical literature, PSIs, and empyemas in particular, have been associated with an increased risk for death, with 29-43% 1-year mortality. However, these studies were small and conducted prior to advances in anti-infective prophylaxis and treatment strategies. Therefore, the purpose of this investigation was to characterize the microbial profile and outcomes of early PSI among lung transplant recipients (LTRs) within the modern era.Figure 1.Isolated organisms from pleural fluid of lung transplant recipients from present study (Panel A, 66 isolates, 2017-2022 transplants) and historical literature (Panel B, 4 studies, 55 isolates, 1983-2005 transplants) Methods This study was approved by the Institutional Review Board of St. Joseph’s Hospital and Medical Center (SJHMC). Included LTRs were transplanted between 2017-2022 at SJHMC with ≥ 1 pleural fluid culture positive for an organism within 90 days of LT. LTRs at SJHMC received cefepime, vancomycin, and levofloxacin in the immediate postoperative period, or targeted antibiotic therapy based on donor and recipient airway cultures. During the index transplant hospitalization, LTRs received prophylaxis with inhaled amphotericin and tobramycin. Additional opportunistic infection prophylaxis throughout the study period included valganciclovir, itraconazole, and trimethoprim/sulfamethoxazole. Results Among 554 total LTRs, 250 (45%) had pleural effusion cultures, and 54 (54/250, 22%) had ≥ 1 pleural culture positive for an organism (Table 1). Over 95% of effusions were exudative and 53% were neutrophil predominant. Of the 66 organisms isolated (Figure 1), 40 (61%) were Gram-positive bacteria, 21 (32%) were fungi (15 Candida species, 6 molds), 4 (6%) were Gram-negative bacteria, and 1 (2%) was unspeciated acid-fast bacilli. Infection was typically managed via effusion drainage and 4-6 weeks of pathogen-directed antimicrobial therapy. All-cause 1-year mortality was 7.4%, lower than national LTR 1-year mortality rates over the study period (∼10-12%). Conclusion In a large investigation of LTRs with early posttransplant PSIs, Gram-positive bacteria were isolated most frequently, with isolation of Candida also common. Gram-negative bacteria comprised a smaller proportion of infections than reported in prior literature. PSIs did not appear to predispose LTRs to poor posttransplant survival. Disclosures Michael D. Nailor, Pharm.D., InflaRx: Advisor/Consultant|Shionogi: Advisor/Consultant

Late-Onset HSV-2 Encephalitis in a Kidney Transplant Recipient: A Rare Case Report

Infections are an important cause of morbidity and mortality in renal transplant recipients. Among the viral pathogens encountered in this population, herpes simplex virus (HSV), a member of the Alphaherpesvirinae subfamily, has an important place. HSV type 2 infections in this immunosuppressed population are primarily due to viral reactivation. While HSV-2 frequently presents as genital herpes or remains asymptomatic, in rare cases, it can lead to severe neurological manifestations, such as encephalitis, particularly in the early post-transplant period with a reported mortality rate of up to 40%. We present the case of a 49-year-old male who, three years after kidney transplantation, developed acute neurological symptoms, including aphasia and disorientation. Polymerase chain reaction (PCR) analysis of cerebrospinal fluid (CSF) identified HSV-2 as the causative pathogen, enabling a swift and accurate diagnosis. The patient was promptly treated with intravenous acyclovir, adjusted for renal function, resulting in complete neurological recovery and subsequent negative follow-up CSF PCR results. This case emphasizes the vital role of PCR diagnostics as the gold standard for confirming viral encephalitis, particularly in immunosuppressed patients, where atypical presentations can complicate diagnosis. It also highlights the importance of considering HSV-2 encephalitis in the differential diagnosis even beyond the immediate post-transplant period. Early recognition and management, facilitated by the multidisciplinary approach, are critical for improving outcomes in this vulnerable patient population.

Safety of ACEI/ARB use in the early (

Data about the safety of ACEI/ARB use in early (<3months) posttransplant period are restricted and remain controversial. This systematic review and meta-analysis included searches of PubMed, Embase and CENTRAL from inception to 31 November 2023, for studies to compare the safety (transplant outcomes and postoperative complications) of ACEI/ARB with non-ACEI/ARB (other antihypertensive medications) initiation in early post kidney transplant period. Of 1,247 citations identified, 13 eligible studies involving 1919 patients were enrolled for analyses. In short- or long-term observations, there were no differences on pooled serum creatinine between ACEI/ARB and non-ACEI/ARB groups whether initiated within 1 or 1-3months posttransplant, however, initiation of ACEI/ARB within the first month posttransplant had an advantage effect on the mean creatinine clearance. Early initiation of ACEI/ARB posttransplant reduced the risks of patient death (RR 0.60, p = 0.009) and graft loss (RR 0.54, p = 0.0002). For postoperative complications, there were no significant differences in acute rejection risk (RR 0.87, p = 0.58), delayed graft function risk (RR 1.00, p = 0.93), hemoglobin level (MD -0.32mg/Dl, p = 0.46) or urinary protein excretion (MD -0.10g/24h, p = 0.16) between two groups. However, the ACEI/ARB group had higher incidence of hyperkalemia (RR 2.43, p = 0.02). Early initiation of ACEI/ARB within 3months posttransplant proved to be basically safe and has renal function recovery benefits, however, hyperkalemia needs to be noted.

Evaluation of the Adherence of Patients to Immunosuppressive Drug Therapy After Liver Transplantation.

Adherence of patients to their immunosuppressive treatment protocol after liver transplant is critical for the health and longevity of the transplanted liver. This study aimed to evaluate and determine the factors affecting the adherence of patients to immunosuppressive therapy after liver transplant. We conducted a cross-sectional descriptive study with patients who had undergone liver transplant in a university hospital between June 2021 and June 2022. Data were collected using a "Patient Identification Form" and the "Immunosuppressive Therapy Adherence Scale." Among our sample of 150 patients, 19.3% (n = 29) did not adhere to their immunosuppressive therapy. A significant correlation was found between adherence to therapy and active employment status or time since transplant (P < .05). Logistic regression analysis indicated that the employment status of patients had a significant effect (2.73-fold) on their adherence to therapy (P = .046). There is a need for frequent evaluation of patient adherence to immunosuppressive therapy starting from the early posttransplant period and a need for information and education to improve adherence by taking into account factors affecting adherence, such as employment status and time since transplant.

Coccidioidomycosis Transmission Through Solid Organ Transplantation (2013-2022): A Report of the Organ Procurement and Transplantation Network ad hoc Disease Transmission Advisory Committee.

Coccidioidomycosis is a fungal infection that poses a serious risk when transmitted through organ transplantation. We analyzed cases reported to the Organ Procurement and Transplantation Network ad hoc Disease Transmission Advisory Committee from 2013 to 2022. Donors and/or recipients who had positive Coccidioides immitis/posadasii serology, pathology, and/or culture were included in this study. Cases adjudicated as 'proven' or 'probable' were analyzed for donor infection risk factors, the timing of infection, transmission by organ type, clinical manifestations, and recipient outcomes. Patient and facility identifiers were removed prior to review. During this time period, 73 potential instances of Coccidioides donor disease transmission events were reported. Among them, infection was transmitted from seven deceased donors to eight recipients. All seven deceased donors had prior infection or exposure to regions where coccidioidomycosis is endemic. Of 20 individuals receiving organs from these donors, eight developed infection, resulting in a 40% transmission rate. The median time to diagnosis post-transplant was 39 days. Disseminated disease occurred in six recipients, five of whom died from the infection. Notably, none of the recipients who received prophylactic antifungal treatment died from the infection. Despite its rarity, donor-derived Coccidioides infection is a serious concern, particularly due to the high mortality rate in the early post-transplant period. To mitigate these risks, a thorough assessment of donor exposure history, coupled with donor serology and bronchoalveolar lavage cultures, can effectively guide post-transplant antifungal prophylaxis. Prompt reporting is crucial to prevent Coccidioides infections among other recipients.

Diagnostic and therapeutic challenges in implementing hypertension management after kidney transplantation.

Evidence for blood pressure (BP) measurement and hypertension management in kidney transplant recipients (KTR) remains lacking. Accurate BP measurement technique is a critical component of hypertension management, and 24-h ambulatory BP monitoring remains the gold standard for diagnosis of hypertension in KTR. BP target at different periods posttransplant is uncertain, but likely higher than that in nontransplant patients given factors related to long-standing uremic milieu and kidney transplantation such as vascular calcification altering transplant renal hemodynamic and allograft perfusion and immunosuppression. Dividing BP target into immediate, early, and late posttransplant periods can guide differential diagnoses of hypertension and BP control with a target SBP less than 160 mmHg in general and BP 115-135/65-85 mmHg for adult KTR receiving pediatric kidneys during the immediate posttransplant period, 130/80 mmHg during early and late posttransplant periods. Calcium channel blockers were shown to have favorable graft outcomes. Novel antihypertensive medications for resistant and refractory hypertension and device-based therapies are limited due to KTR's ineligibility for participating in clinical trials. In KTR, BP measurement and monitoring practice should follow the standard clinical practice guideline for nontransplant patients by considering posttransplant factors and immunosuppressive state. Novel treatment options required further studies.

Safety of the reduced fixed dose of mycophenolate mofetil confirmed via therapeutic drug monitoring in de novo kidney transplant recipients.

Mycophenolate mofetil (MMF) is usually prescribed with a reduced fixed dose in Asian kidney transplant recipients (KTRs). However, the clinical efficacy and safety of the fixed dose have not yet been investigated via therapeutic drug monitoring. We evaluated whether reduced fixed-dose MMF is an optimal dosing strategy to achieve the therapeutic target of mycophenolic acid (MPA) exposure in Korean KTRs. This open-label, prospective study enrolled 50 de novo KTRs prescribed with tacrolimus, corticosteroid, and fixed-dose MMF (1.0-1.5 g/day). The trough level (C0) and area under the curve (AUC0-12 hr) of MPA were measured at 1 and 24 weeks after kidney transplantation (KT). The relationship of body weight (BW)-adjusted MMF dose with MPA C0 and MPA AUC0-12 hr was assessed using linear regression analysis. The initial fixed dose of MMF of 1.44 ± 0.16 g/day was adjusted in 24 patients (48.0%) and then reduced to a mean dose of 1.19 ± 0.31 g/day at 24 weeks after KT. Most patients (≥84.0%) attained the minimum required MPA C0 of 1.0 μg/mL and MPA AUC0-12 hr of 30 μg × hr/mL at 1 and 24 weeks. The BW-adjusted MMF dose demonstrated significant positive correlations with MPA C0 and MPA AUC0-12 hr at 1 and 24 weeks after KT. Moreover, 14 patients (28.0%) reported MPA-related adverse events that were predictable based on MPA AUC0-12 hr (cutoff level, 46.4 μg × hr/mL). The current reduced fixed-dose MMF strategy can help achieve the therapeutic target of MPA exposure in tacrolimus-treated Korean KTRs during the early posttransplant period.

Pre-transplant Serum Procalcitonin as a Predictor of Early Post-transplant Sepsis and Mortality After Living Donor Liver Transplantation: A Prospective Observational Study.

The early post-transplant period after liver transplantation is critical, as recipients are highly susceptible to sepsis due to their immune-compromised state. This study aimed to identify the association between preoperative procalcitonin and early post-transplant sepsis and mortality at one month after living donor liver transplantation (LDLT). Allpatients who underwent LDLT from July 2021 to December 2021 were recruited prospectively. Participants were divided into two groups based on preoperative PCT levels: elevated (>0.5 ng/ml) and low levels (<0.5 ng/ml). Serum procalcitonin (PCT) levels were measured on the day of transplant and on postoperative days 3 and 7. The relationship between preoperative PCT and post-transplant sepsis was evaluated using a Chi-square test, and receiver operating characteristic (ROC) curves were generated. Sepsis occurred in 48.3% of patients, with a significant association between elevated preoperative PCT levels and early post-transplant sepsis (p=0.023). The ROC curve for preoperative PCT showed moderate predictive ability (area under curve (AUC)=0.664), while PCT levels on postoperative day 3 demonstrated better discriminatory power (AUC=0.790). PCT levels measured on day 7 also had good diagnostic accuracy, with an AUC of 0.843 and a significant difference between the sepsis and non-sepsis groups (p=0.002). The length of ICU stay was significantly longer in the sepsis group (p=0.009). Conclusion: Elevated preoperative PCT levels can predict early post-transplant sepsis in LDLT patients. PCT monitoring may enhance risk stratification and guide perioperative management, improving post-transplant outcomes.

Biodegradable internal biliary stenting in orthotopic liver transplantation – A feasibility study

IntroductionBiliary complications remain a common cause of morbidity after liver transplantation and often require invasive interventions to manage. We aimed to assess the technical feasibility and safety of placement of a biodegradable stent across the biliary anastomosis at the time of liver transplantation in patients having a duct to duct biliary reconstruction. MethodsFor this prospective, single-arm, descriptive study, 10 consecutive patients undergoing whole graft, deceased donor, liver transplantation and duct-to-duct biliary tract reconstruction were enrolled and a biodegradable biliary stent was sutured into the bile duct across the anastomosis. ResultsIn all 10 patients it was technically feasible to place and secure the stent safely during the operation. After >6 months (median of 212 days) follow up, no patients had developed biliary anastomotic stricture. One patient had transient bile leak immediately post-operative that was managed conservatively. One patient required endoscopic intervention for non-anastomotic stricture development and biliary cast material that had resulted in stent dysfunction. DiscussionThe results of this study suggest surgical feasibility of placement of an absorbable biliary stent across the biliary anastomosis at the time of liver transplantation, as well as an acceptable safety profile. Further studies are required to confirm these safety and feasibility findings and to assess efficacy in reducing rates of biliary complications and the need for endoscopic intervention in the early post-transplant period.

Epidemiology and Outcomes of Recurrent C Difficile Infection Among Hematopoietic Cell Transplant Recipients: A Single-center, Retrospective 10-year Study.

There are limited data on the contemporary epidemiology of recurrent Clostridioides difficile infection (CDI) among hematopoietic cell transplant (HCT) recipients. We aimed to determine the incidence, risk factors, and outcomes for recurrent CDI among HCT recipients. We conducted a retrospective study of adult HCT recipients between 2012 and 2021 diagnosed with index CDI between HCT day -7 and +100. Recurrent CDI was defined as new symptoms and a positive test within 12 weeks after treatment for index CDI. Cox proportional hazards models were used to investigate associations between prespecified variables (age, neutropenia, exposure to antibiotics with antianaerobic coverage, cytomegalovirus viremia/disease, and metronidazole monotherapy) and recurrent infection, presented as hazard ratios with 95% confidence intervals (CI). Of 3479 HCT recipients, 416 (12%) had index CDI and were treated with oral vancomycin (31%), metronidazole (41%), oral vancomycin and metronidazole (29%). Of 381 patients eligible for recurrent CDI analysis, 35 had recurrent infection; cumulative incidence was 10% (95% CI, 7-13) at 12 weeks. In the 14 days after recurrence, 2/25 (8%) patients required hospital admission; none died within 30 days. Metronidazole monotherapy for treatment of index CDI was associated with an increased rate of recurrence (adjusted hazard ratio, 2.0; 95% CI, 1.0-4.0; P = .048). Recurrent CDI occurred in 10% of HCT recipients in the early posttransplant period and was associated with use of metronidazole. Further study is needed to characterize risk factors for recurrent CDI among HCT recipients to guide use of agents aimed at preventing recurrence.

Management of Early Post-Transplant Hyperglycemia by Dedicated Endocrine Care Improves Glycemic Outcomes.

Early post-transplant hyperglycemia (EPTH) is an independent risk factor for hospital readmissions, acute rejection, infections and developing post-transplant diabetes mellitus (PTDM). Close glycemic control is prudent in the early post-transplant period. The management of EPTH was evaluated among a cohort of kidney transplant recipients, who either received routine care (RC) or dedicated endocrine care (DEC). A retrospective analysis was conducted on kidney transplant recipients from 2019 to 2023. The impact of DEC on post-transplant glycemic control was investigated. Hospitalized patients receiving post-transplant insulin therapy were included. DEC involved at least twice-daily blood glucose (BG) assessment by an endocrinologist, while the RC received usual care. A mixed-model analysis was employed to assess differences in BG trajectories between DEC and RC over an eight-day period. Additionally, various glycemic control metrics were compared, including glucose variability, time-in-range for target BG, rates of hypoglycemia and response to hyperglycemia. The cohort comprised 113 patients. In the DEC group, 91% had pre-transplant DM compared to 15% in the RC group (p < 0.001). Patients under DEC had higher baseline BG and glycated hemoglobin compared to those under RC (p < 0.001, for both). The DEC group displayed a lower trajectory of BG over time compared to the RC group (p = 0.002). Patients under DEC were more likely to receive insulin if BG measured above 200 mg/dL (66% vs. 46%) and displayed less below-range BG (<110 mg/dL) compared to those under RC (12.9% vs. 23.6%, p < 0.001). Management of EPTH by DEC improves glycemic outcomes in renal transplant recipients.

Guiding the starting dose of the once-daily formulation of tacrolimus in "de novo" adult renal transplant patients: a population approach.

The once-daily extended-release tacrolimus formulation (ER-Tac) has demonstrated similar efficacy and safety to the twice-daily immediate-release formulation (IR-Tac), but few population-based pharmacokinetic models have been developed in de novo kidney transplant patients to optimize doses. Therefore, this study aimed i) at developing a population pharmacokinetic model for ER-Tac in de novo adult kidney transplant patients ii) and identifying genetic factors and time-varying covariates predictive of pharmacokinetic variability to guide tacrolimus dosage during the early post-transplant period. A total of 1,067 blood tacrolimus concentrations from 138 kidney transplant patients were analyzed. A total of 29 out of 138 patients were intensively sampled for 24h on the day 5 post-transplantation; meanwhile, for the remaining patients, concentrations were collected on days 5, 10, and 15 after transplantation. Tacrolimus daily doses and genetic and demographic characteristics were retrieved from the medical files. Biochemistry time-varying covariates were obtained on different days over the pharmacokinetic (PK) study. A simultaneous PK analysis of all concentrations was carried out using the non-linear mixed-effects approach with NONMEM 7.5. A two-compartment model with linear elimination and delayed absorption best described the tacrolimus pharmacokinetics. Between-patient variability was associated with oral blood clearance (CL/F) and the central compartment distribution volume (Vc/F). Tacrolimus concentrations standardized to a hematocrit value of 45% significantly improved the model (p < 0.001). This method outperformed the standard covariate modeling of the hematocrit-blood clearance relationship. The effect of the CYP3A5 genotype was statistically (p < 0.001) and clinically significant on CL/F. The CL/F of patients who were CYP3A5*1 carriers was 51% higher than that of CYP3A5*1 non-carriers. Age also influenced CL/F variability (p < 0.001). Specifically, CL/F declined by 0.0562 units per each increased year from the value estimated in patients who were 60years and younger. The 36% between-patient variability in CL/F was explained by CYP3A5 genotype, age, and hematocrit. Hematocrit standardization to 45% explained the variability of tacrolimus whole-blood concentrations, and this was of utmost importance in order to better interpret whole-blood tacrolimus concentrations during therapeutic drug monitoring. The dose requirements of CYP3A5*/1 carriers in patients aged 60years or younger would be highest, while CYP3A5*/1 non-carriers older than 60years would require the lowest doses.

Evaluation of Virtual Care in Kidney Transplant Recipients in the Early Posttransplant Period.

Though virtual care was widely adopted during the COVID-19 pandemic, evidence to support its use in kidney transplant recipients early after transplantation is limited. We conducted a retrospective cohort study comparing post kidney transplant outcomes in patients who received in-person transplant care before the COVID-19 pandemic with those who received mainly virtual transplant care during the COVID-19 pandemic. The usual-care group included 69 patients who received a kidney transplant from March 1, 2019 to September 1, 2019, and the virtual-care group included 64 patients who received a kidney transplant from September 1, 2020 to March 1, 2021. At 6 months, five patients in the usual-care group and three patients in the virtual-care group died. There was one graft loss and one episode of acute rejection in the usual-care group, and two episodes of acute rejection in the virtual-care group (p = 0.60). Estimated glomerular filtration rate was higher for patients in the virtual-care group (59mL/min/1.73m2 vs. 52mL/min/1.73m2, p = 0.046) and serum creatinine was not different (138 µmol/L vs. 127µmol/L, p = 0.27). There was no difference in mean blood pressure or hospitalizations. Outcomes were similar among recipients of a kidney transplant prior to the COVID-19 pandemic when care was mainly in person and during the pandemic when care was mainly virtual, without a signal of harm. Patient and donor selection may have led to unmeasured differences between groups.

Machine-learning model to predict the tacrolimus concentration and suggest optimal dose in liver transplantation recipients: a multicenter retrospective cohort study

Titrating tacrolimus concentration in liver transplantation recipients remains a challenge in the early post-transplant period. This multicenter retrospective cohort study aimed to develop and validate a machine-learning algorithm to predict tacrolimus concentration. Data from 443 patients undergoing liver transplantation between 2017 and 2020 at an academic hospital in South Korea were collected to train machine-learning models. Long short-term memory (LSTM) and gradient-boosted regression tree (GBRT) models were developed using time-series doses and concentrations of tacrolimus with covariates of age, sex, weight, height, liver enzymes, total bilirubin, international normalized ratio, albumin, serum creatinine, and hematocrit. We conducted performance comparisons with linear regression and populational pharmacokinetic models, followed by external validation using the eICU Collaborative Research Database collected in the United States between 2014 and 2015. In the external validation, the LSTM outperformed the GBRT, linear regression, and populational pharmacokinetic models with median performance error (8.8%, 25.3%, 13.9%, and − 11.4%, respectively; P < 0.001) and median absolute performance error (22.3%, 33.1%, 26.8%, and 23.4%, respectively; P < 0.001). Dosing based on the LSTM model’s suggestions achieved therapeutic concentrations more frequently on the chi-square test (P < 0.001). Patients who received doses outside the suggested range were associated with longer ICU stays by an average of 2.5 days (P = 0.042). In conclusion, machine learning models showed excellent performance in predicting tacrolimus concentration in liver transplantation recipients and can be useful for concentration titration in these patients.

Novel Potassium Binders for Early Postoperative Hyperkalemia in Kidney Transplant Recipients: A Single-Center Experience

PurposeEvaluate the safety/efficacy of novel potassium binders (patiromer, sodium zirconium cyclosilicate [SZ-9]) for early postoperative hyperkalemia following kidney transplantation. MethodsRetrospective, single-center, cohort study of deceased-donor kidney recipients transplanted between 1/2018 and 12/2020. Potassium-binder use was evaluated from immediately posttransplant until discharge. Potassium binders were administered ≥2 hours before/after medications. ResultsA total of 179 patients were included, 24 (13%) of whom received potassium binders (16 [67%] patiromer, 7 [29%] SZ-9, 1 [4%] both) for a mean of 2.5 (±3.18) doses. Peak potassium levels were higher in the potassium-binder group (6.05 vs 5.35 mEq/L; P < .001). More patients on potassium binders transitioned to atovaquone than those on no binders (n = 21 [100%] vs n = 112 [75%], respectively; P = .005). Delayed graft function (DGF) was observed in 100 (56%) patients, with a higher proportion receiving potassium binders (18 [75%] vs 82 [53%], respectively; P = .042). There was no difference between groups in number of posttransplant dialysis sessions required in the general study population (P = .2), nor in the DGF group (P = .12). No difference was noted in the incidence of ileus (P = .2), or gastrointestinal symptoms (diarrhea, nausea, vomiting; P = .6). Of the 24 patients who received inpatient binders, 9 (37.5%) were discharged and remained on them for a mean of 46 (±49) days. ConclusionPatiromer and SZ-9 appear safe in the early posttransplant period, but larger prospective trials are needed. Potassium-binder use does not appear to be associated with fewer dialysis sessions in DGF patients, however, they may be used as additional tools for lowering potassium in these patients.

Perioperative Use of IgM-Enriched Immunoglobulins in Liver Transplantation Recipients at High Risk for Infections: A Preliminary Study.

Background: Infections frequently occur after orthotopic liver transplantation (OLT) and are associated with increased mortality. In 2018, we introduced perioperative administration of intravenous immunoglobulin enriched in IgM as an optional therapy in recipients at a high risk of infection. This preliminary study evaluated whether this preparation reduced infections in the early post-transplantation period. Methods: Adult patients with a high risk of postoperative infections who underwent OLT between January 2014 and December 2021 in our center were included in the study. The primary outcome was the occurrence of new postoperative bacterial and fungal infections within the first 30 days after OLT. Results: Ninety recipients at a high risk of postoperative infections who underwent OLT were included, of whom 51 (57%) received IgM preparation. Patients treated and not treated with IgM were similar in terms of demographics, model of end-stage liver disease score, and risk factors for postoperative infections. The occurrence of new infections was lower (absolute risk reduction (ARR) 21.2%; p = 0.038) in patients who received IgM than in those who did not. Multivariate analysis adjusted for confounders (OR 0.348; p = 0.033) and propensity score-based matching analysis (ARR 21.2%, p = 0.067) confirmed an association between IgM preparation and lower occurrence of postoperative infections. The 90-day mortality rate was lower (ARR 13.4%, p = 0.018) in patients who received IgM preparation. Conclusions: In OLT recipients at high risk for infections, perioperative administration of an IgM-enriched preparation seems to reduce the development of new infections within the first 30 days after OLT.

Time-dependent analysis of erectile dysfunction in kidney transplant recipients: insights from four distinct time periods

Background and intentionErectile dysfunction (ED) is an underappreciated clinical condition in men. This study aims to compare the dynamic changes in the distribution of ED among male kidney transplant recipients (mKTRs) in four epochs: end-stage renal disease period (ESRDp), early post-transplant period (EPTP), pre-COVID-19, and post-COVID-19.MethodsGeneral information was gathered through interviews, follow-ups, and medical records. The International Index of Erectile Function Questionnaire-5 was used to assess erectile function. The Mann–Whitney U test and chi-square test were used to analyze differences in ED strength. Univariate and logistic regression analyses were conducted to identify risk factors for ED.ResultsThe database contains 230 mKTRs. In the ESRDp, 17.0% had normal erectile function, 53.5% had mild ED, 18.3% had moderate ED, and 11.3% had severe ED. In the EPTP, the distribution was 38.2% normal, 42.6% mild, 10.8% moderate, and 8.2% severe. In the pre-COVID-19 period, it was 34.3%, 47.3%, 10.4%, and 7.8%, and in the post-COVID-19 period, it was 23.0%, 45.6%, 21.3%, and 10.0%. Overall, erectile function improved after kidney transplant (KT). However, post-COVID-19, the proportion of erectile function significantly decreased compared to EPTP and pre-COVID-19 periods. Risk factors for post-pandemic ED included degree, Generalized Anxiexy Disorder-7, kidney donor type, postoperative time, hypertension and hemoglobin concentration.ConclusionKT improves erectile function in mKTRs within 5 years, but post-SARS-CoV-2 viral infection, ED worsens due to altered risk factors. These findings inform future research for comprehensive ED prevention and management strategies in this population.

CD70 identifies alloreactive T cells and represents a potential target for prevention and treatment of acute GVHD

AbstractGraft-versus-host disease (GVHD) remains a major challenge after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and further understanding of its immunopathology is crucial for developing new treatments. CD70 interacts with CD27 and is upregulated transiently on T cells after recent T-cell receptor (TCR) engagement. Here, we investigated the functional and clinical significance of CD70 expression on T cells during the early posttransplantation period. CD70 was expressed on a subset of highly activated memory T cells within the first 2 weeks after transplant, which then gradually declined in most patients. CD70+ T cells exhibited an open chromatin landscape and a transcriptional profile indicative of intense Myelocytomatosis oncogene (MYC)-driven glycolysis and proliferation. CD4+ and CD8+CD70+ T-cell numbers increased by ninefold and fourfold, respectively, during acute GVHD (aGVHD) and displayed an oligoclonal TCR repertoire. These cells expressed CCR4 and CCR6 chemokine receptors and were markedly increased in aGVHD tissue samples. Furthermore, CD70+ T cells demonstrated alloreactive specificity in vitro, and proliferative and inflammatory cytokine responses were markedly attenuated by CD70 blockade. These findings identify CD70 as a marker of highly activated alloreactive T cells and reveal the potential therapeutic importance of inhibiting CD27-CD70 costimulation in both the prophylaxis and treatment of aGVHD.

Clinical approach to donor-derived infection in solid organ transplant recipients.

Donor-derived infection is an uncommon but potentially devastating complication of solid organ transplantation (SOT). Accurate and timely identification of unexpected infectious disease transmission events has implications not only for the recipient(s) experiencing infection, but also other recipients of organs or tissues from the same donor who may require additional testing or risk mitigation, as well as the broader organ transplant regulatory framework. This narrative review synthesizes data from published reports of symptomatic unexpected donor-derived infections in SOT recipients to provide clinicians with a systematic approach to the evaluation of undifferentiated illnesses that may be of donor origin. Key reasons to consider donor-derived infection include certain microbiologically proven infections in the recipient, especially early after transplant, characteristics of the donor or their management that suggest potential exposure to or infection with specific pathogens prior to organ procurement, and select clinical syndromes that occur in the post-transplant period. Syndromes for which expedited consideration and evaluation of donor-derived infection may be warranted include central nervous system infection, graft or perigraft complications developing in the absence of typical risk factors, and unexplained critical illness/sepsis syndrome in the early post-transplant period. When embarking on an investigation of a suspected donor-derived infection, clinicians should apply knowledge of the entire continuum of the organ procurement and transplant process to ensure unbiased and comprehensive data collection that will facilitate appropriate adjudication of these uncommon but high-consequence events.

Immature platelet fraction levels predict the development of prolonged thrombocytopenia after haematopoietic stem cell transplantation

Prolonged thrombocytopenia (PT) is a serious complication after haematopoietic stem cell transplantation (HSCT). PT has been suggested to be associated with an increased platelet transfusion requirement and poor outcomes after transplantation. Due to the complex mechanism of PT development, it is difficult to diagnose in the early post-transplant period. Our study aimed to identify an early predictive marker for PT after HSCT. Previous studies showed that the clinical utility of immature platelet fraction (IPF) predicts platelet recovery after chemotherapy and successful engraftment. However, the relationship between IPF and PT after HSCT remains unclear. Fifty-two patients with malignant haematological diseases who underwent HSCT were included in the study. We observed the kinetics of recovery of haematological parameters after transplantation and performed receiver operating characteristics (ROC) curve analysis using data from the 52 HSCT patients. The days to rise and peak of IPF, absolute IPF count (A-IPF) and highly fluorescent IPF (H-IPF) were almost synchronised in all patients, at day 10 and day 15, respectively. The begin to rise levels of IPF, H-IPF and A-IPF were all significantly lower in the PT group than in the good engraftment (GE) group (p=0.0016, p=0.0094, p=0.0086, respectively). The peak levels of IPF were significantly lower in the PT group than the GE group (p=0.0036). However, the peaks of H-IPF and A-IPF were not statistically significant between the two groups (p=0.3383, p=0.0887, respectively). The area under the ROC curve (AUC) of IPF rise was 0.739 (95% CI 0.583-0.896; p<0.05) and the cut-off value was 3.5%, while the AUC of IPF peak was 0.800 (95% CI 0.637-0.962; p<0.01) and the cut-off value was 8.0%. In conclusion, early low levels of IPF predict the development of PT after HSCT. These findings may help improve the management and treatment strategies for PT after HSCT.