Anti-HLA serologic response to CD38-targeting desensitization therapy is challenged by peripheral memory B cells in highly sensitized kidney transplant candidates.

High human leukocyte antigen (HLA) sensitization limits access to compatible transplantation. New CD38-targeting agents have been shown to reduce anti-HLA antibodies, although with important interpatient variability. Thus, pretreatment identification of responder and nonresponder (NR) patients is needed for treatment decision-making. We analyzed 26 highly sensitized (HS) patients from 2 desensitization trials using anti-CD38 monoclonal antibodies. Hierarchical clustering identified 3 serologic responder groups: high responders, low responders, and NR. Spectral flow cytometry and functional HLA-specific memory B cell (mBC) assessment were first conducted on peripheral blood mononuclear cells and bone marrow samples from 16 patients treated with isatuximab (NCT04294459). Isatuximab effectively depleted bone marrow plasma cells, peripheral CD38-expressing plasmablasts, plasma cells, transitional B cells, and class-switch mBCs, ultimately reducing frequencies of HLA-specific immunoglobulin G (IgG)-producing mBCs. Multidimensional spectral flow cytometry with partial least squares discriminant analysis revealed that pretreatment abundance of specific circulating mBC phenotypes, especially CD38neg class-switch mBCs, accurately distinguished between high serologic responders and low responders or NR (AUC 0.958, 0.860-1.000, P = .009), who also displayed significantly lower frequencies of HLA-specific IgG-producing mBCs (P < .0001). This phenotypical mBC signature predicting response to therapy was validated in an external HS patient cohort (n = 10) receiving daratumumab (NCT04204980). This study identifies critical circulating mBC subset phenotypes that distinguish HS patients with successful serologic responses to CD38-targeting desensitization therapies, potentially guiding treatment decision-making.

A nursing perspective on inpatient sleep and circadian disruptions for pediatric stem cell transplant patients.

BACKGROUND: Children treated with stem cell transplant (SCT) are routinely hospitalized for long periods where they are exposed to significant sleep and circadian disruptions. As nurses play a primary role in symptom management during SCT, we sought to understand their perspective on patient sleep and circadian disruptions, perceived barriers to a good sleep and circadian environment, and suggestions for improvement. PROCEDURE: Four focus groups were conducted with pediatric SCT nurses (N = 25 participants). A semistructured focus group guide was administered, with the discussions recorded and transcribed. A multistage thematic analysis combining prefigured and emergent dimensions was conducted. Our analysis focused on drawing comparisons within and across focus groups to understand the unique work experiences that participants had related to the patient's sleep and circadian environment. RESULTS: Three key themes emerged. First, nurses expressed a high awareness of how disruptive the hospital environment is for patients. Second, nurses described their extensive efforts to try to minimize the impact of these disruptions. Finally, they provided clear recommendations for how to improve upon these concerns, along with barriers that they perceive could impede implementation. CONCLUSIONS: Front-line caregivers on a pediatric SCT unit describe key contributors to sleep/circadian disturbances for patients. Within the constraints of the considerable medical needs of this patient population and the physical room/hospital environment, nurses strive to minimize these disruptions to the best of their ability. It is crucial that hospitals assess and remediate these disturbances for these children that have important implications for overall health.

Glucocorticoids as a risk factor for infection and adverse outcomes in non-HIV and non-transplant patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM), an opportunistic fungal infection affecting immunocompromised hosts, leads to high mortality. The role of previous exposure to glucocorticoids as a risk factor and as an outcome modulator has been observed, but systematic studies are lacking. OBJECTIVE: The primary aim of this study is to evaluate the impact of glucocorticoid use on the clinical outcomes, specifically mortality, of non-HIV and non-transplant (NHNT) patients diagnosed with CM. METHODS: We queried a global research network to identify adult NHNT patients with CM based on ICD codes or recorded specific Cryptococcus CSF lab results with or without glucocorticoid exposure the year before diagnosis. We performed a propensity score-matched analysis to reduce the risk of confounding and analysed outcomes by glucocorticoid exposure. We used a Cox proportional hazards model for survival analysis. RESULTS: We identified 764 patients with a history of glucocorticoid exposure and 1267 patients without who developed CM within 1 year. After propensity score matching of covariates, we obtained 627 patients in each cohort. The mortality risk in 1 year was greater in patients exposed to prior glucocorticoids (OR: 1.3, CI: 1.2-2.0, p = 0.002). We found an excess of 45 deaths among CM patients with previous glucocorticoid use (7.4% increased absolute risk of dying within 1 year of diagnosis) compared to CM controls without glucocorticoid exposure. Hospitalisation, intensive care unit admission, emergency department visits, stroke and cognitive dysfunction also showed significant, unfavourable outcomes in patients with glucocorticoid-exposed CM compared to glucocorticoid-unexposed CM patients. CONCLUSIONS: Previous glucocorticoid administration in NHNT patients seems to associate with 1-year mortality after CM adjusted for possible confounders related to demographics, comorbidities and additional immunosuppressive medications. Serial CrAg screening might be appropriate for higher-risk patients on glucocorticoids after further cost-benefit analyses.

Mediating role of inner strength in the relationship between medication literacy and medication adherence among kidney transplant patients. / å† åœ¨åŠ›é‡åœ¨è‚¾ç§»æ¤æ‚£è€ è¯ç‰©ç´ å »ä¸Žæœè¯ä¾ä»Žæ€§å ³ç³»ä¸­çš„ä¸­ä»‹ä½œç”¨ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Compared with long-term renal replacement therapy, kidney transplantation is the ideal treatment for end-stage renal disease (ESRD), significantly extending patient life and improving quality of life. Kidney transplant patients need to adhere to lifelong immunosuppressive medication regimens, but their medication adherence is generally poor compared with other organ transplant recipients. Medication adherence is closely related to medication literacy and psychological status, yet related studies are limited. This study aims to investigate the current status of medication adherence, inner strength, and medication literacy in kidney transplant patients, analyze the relationships among these 3 factors, and explore the mediating role of inner strength in the relationship between medication literacy and medication adherence. METHODS: A cross-sectional survey was conducted from March to October 2023 involving 421 patients aged≥18 years who visited kidney transplantation outpatient clinics at 4 tertiary hospitals in Hunan Province. The inner strength, medication literacy, and medication adherence of kidney transplant patients were investigated using the Inner Strength Scale (ISS), the Chinese version of the Medication Literacy Assessment in Spanish and English (MedLitRxSE), and the Chinese version of the Morisky Medication Adherence Scale-8 (C-MMAS-8), respectively. Univariate analysis was performed to examine the effects of demographic and clinical data on medication adherence. Correlation analysis was conducted to explore the relationships among medication literacy, medication adherence, and inner strength. Significant variables from univariate and correlation analyses were further analyzed using multiple linear regression, and the mediating effect of inner strength was explored. RESULTS: Among the 421 questionnaires collected, 408 were valid, with an effective rate of 96.91%. The scores of C-MMAS-8, MedLitRxSE, and ISS were 6.64±1.16, 100.63±14.67, and 8.47±4.03, respectively. Among the 408 patients, only 86 (21.08%) patients had a high level of medication adherence, whereas 230 (56.37%) patients had a medium level of medication adherence, and 92 (22.55%) patients had poor medication adherence. Univariate analysis indicated that the kidney transplant patients' age, marital status, education levels, years since their kidney transplant operation, number of hospitalizations after the kidney transplant, and adverse drug reactions showed significant differences in medication adherence (all P<0.05). Correlation analysis showed that inner strength positively correlated with both medication literacy (r=0.183, P<0.001) and medication adherence (r=0.201, P<0.001). Additionally, there was a positive correlation between medication adherence and medication literacy (r=0.236, P<0.001). Inner strength accounted for 13.22% of the total effect in the mediating role between medication literacy and medication adherence. CONCLUSIONS: The level of medication adherence among kidney transplant patients needs improvement, and targeted intervention measures are essential. Inner strength mediates the relationship between medication literacy and medication adherence in these patients. Healthcare professionals should focus on enhancing medication literacy and supporting patients' inner strength to improve medication adherence.

Cytomegalovirus drug resistance mutations in transplant recipients with suspected resistance.

Resistant CMV infections are challenging complications after SOT and HSCT. Prompt recognition of ARMs is imperative for appropriate therapy. 108 plasma samples from 96 CMV + transplant recipients with suspected resistance were analysed in CNM in a retrospective nationwide study from January 2018 to July 2022 for resistance genotyping. ARMs in UL97 and UL54 were found in 26.87% (18/67) and 10.60% (7/66) of patients, respectively. Patients' ARM distribution in UL97 was as follows: L595S n = 3; L595S/M460I n = 1; L595S/N510S n = 1; L595W n = 1; C603W n = 4; A594V n = 3; A594E n = 1; C607Y n = 1; L397R/T409M/H411L/M460I n = 1; L397I n = 1; H520Q n = 1; four patients showed ARMs in UL54 as well (F412C n = 1; T503I n = 2; P522S n = 1), whereas three patients exhibited ARMs in UL54 only (L501I/T503I/L516R/A834P n = 1; A987G n = 2). L516R in UL54 and L397R/I and H411L in UL97 have been found for the first time in a clinical sample. L595S/W was the most prevalent ARM found to lend resistance to GCV. In UL54 all ARMs lent resistance to GCV and CDV. In addition, A834P, found in one patient, also lent resistance to FOS. CMV load did not differ significantly in patients with or without ARMs, and no differences were found either between patients with ARMs in UL97 or in UL97 and UL54. Despite extensive use of classical antivirals for the treatment of CMV infection after HSCT and SOT, ARMs occurred mainly in viral UL97 kinase, which suggests that CDV and mostly FOS continue to be useful alternatives to nucleoside analogues after genotypic detection of ARMs.

Extra-urogenital infection by Mycoplasma hominis in transplant patients: two case reports and literature review.

BACKGROUND: Mycoplasma hominis is a facultative anaerobic bacterium commonly present in the urogenital tract. In recent years, M. hominis has increasingly been associated with extra-urogenital tract infections, particularly in immunosuppressed patients. Detecting M. hominis in a diagnostic laboratory can be challenging due to its slow growth rate, absence of a cell wall, and the requirements of specialized media and conditions for optimal growth. Consequently, it is necessary to establish guidelines for the detection of this microorganism and to request the appropriate microbiological work-up of immunosuppressed patients. CASE PRESENTATION: We hereby present two cases of solid organ transplant patients who developed M. hominis infection. Microscopic examination of the bronchial lavage and pleural fluid showed no microorganisms. However, upon inoculating the specimens onto routine microbiology media, the organism was successfully identified and confirmation was performed using 16S rDNA sequencing. Both patients received appropriate treatment resulting in the resolution of M. hominis infection. CONCLUSIONS: The prompt detection of M. hominis in a clinical specimen can have a significant impact on patient care by allowing for early intervention and ultimately resulting in more favorable clinical outcomes, especially in transplant patients.

Population pharmacokinetic analyses of tacrolimus in non-transplant patients: a systematic review.

BACKGROUND AND OBJECTIVES: Tacrolimus (TAC) has been increasingly used in patients with non-transplant settings. Because of its large between-subject variability, several population pharmacokinetic (PPK) studies have been performed to facilitate individualized therapy. This review summarized published PPK models of TAC in non-transplant patients, aiming to clarify factors affecting PKs of TAC and identify the knowledge gap that may require further research. METHODS: The PubMed, Embase databases, and Cochrane Library, as well as related references, were searched from the time of inception of the databases to February 2023, to identify TAC population pharmacokinetic studies modeled in non-transplant patients using a non-linear mixed-effects modeling approach. RESULTS: Sixteen studies, all from Asian countries (China and Korea), were included in this study. Of these studies, eleven and four were carried out in pediatric and adult patients, respectively. One-compartment models were the commonly used structural models for TAC. The apparent clearance (CL/F) of TAC ranged from 2.05 to 30.9 L·h-1 (median of 14.9 L·h-1). Coadministered medication, genetic factors, and weight were the most common covariates affecting TAC-CL/F, and variability in the apparent volume of distribution (V/F) was largely explained by weight. Coadministration with Wuzhi capsules reduced CL/F by about 19 to 43%. For patients with CYP3A5*1*1 and *1*3 genotypes, the CL/F was 39-149% higher CL/F than patients with CYP3A5*1*1. CONCLUSION: The optimal TAC dosage should be adjusted based on the patient's co-administration, body weight, and genetic information (especially CYP3A5 genotype). Further studies are needed to assess the generalizability of the published models to other ethnic groups. Moreover, external validation should be frequently performed to improve the clinical practicality of the models.

Effects of empowerment education on the self-management and self-efficacy of liver transplant patients: a randomized controlled trial.

BACKGROUND: Despite the increasing survival rates, liver transplant patients experience numerous postoperative complications and encounter significant challenges in long-term self-management. This study aims to examine the effectiveness of empowerment education in enhancing self-management skills and self-efficacy among liver transplant recipients. METHODS: A randomized, single-blind, single-center trial was conducted in China between August 2019 and September 2020, involving liver transplant recipients. The intervention group received 12 weeks of empowerment education, while the control group received 12 weeks of routine education. .The study assessed the patients' self-management and self-efficacy using the Liver Transplant Recipient Self-Management Questionnaire and the Self-efficacy for Managing Chronic Disease 6-Item Scale. Follow-up assessments were conducted at 1, 3, and 6 months after the intervention. RESULTS: Eighty-four patients were initially randomized to either the intervention group (n1 = 42) or the routine education group (n2 = 42). Twelve patients were excluded from the analysis due to loss of follow-up or discontinuation of the intervention, leaving 72 patients (n1 = 35, n2 = 37) for the final analysis. The scores for exercise and lifestyle management were significantly higher in the intervention group than in the control group at 1, 3, and 6 months after the intervention (t = 3.047, 5.875, 8.356, and t = 5.759, 4.681, 11.759, respectively; P < 0.05). At 3 and 6 months after the intervention, the scores for cognitive symptom management, communication with physicians, and self-efficacy were significantly higher in the intervention group than in the control group (t = 5.609, 6.416, and t = 5.576, 11.601, and t = 6.867, 15.071, respectively; P < 0.001). Within the intervention group, self-management scores increased significantly over time, while within the control group, the scores for communication with physicians, lifestyle, and self-efficacy showed a significant decline from 3 to 6 months after routine health education. CONCLUSIONS: The results of this study suggest that empowerment education is an effective means of improving the self-management and self-efficacy of liver transplant patients, with better outcomes compared to routine health education. These findings have important implications for nursing practice and provide valuable guidance for clinical education of liver transplant patients. TRIAL REGISTRATION: ChiCTR2200061561.

Higher incidence of neurotoxicity and skin hyperpigmentation in renal transplant patients treated with polymyxin B.

BACKGROUND: Toxicity is a major concern related to the clinical use of polymyxin B, and available safety data for renal transplant patients are limited. AIMS: We investigated the safety of polymyxin B and toxicity risk factors in renal transplant patients. METHODS: A prospective study was performed on a group of renal transplant patients who received intravenous polymyxin B between January 2018 and August 2021. Polymyxin B treatment was monitored to evaluate toxicity and risk factors. RESULTS: A total of 235 courses of polymyxin B were administered to 213 patients. Of these, 121 (51.5%) developed skin hyperpigmentation (SH), 149 (63.4%) developed neurotoxicity and 10 (5.5%) developed acute kidney injury of which 80% was reversible. Risk factors for developing SH included a high total dose by weight (odds ration [OR] 1.31, 95% confidence interval [CI] 1.08-1.60, P = .008) and the presence of neurotoxicity (OR 2.86, 95% CI 1.56-5.26, P = .001). Neurotoxicity manifested during the first 2 days of treatment. Neurotoxicity occurred most commonly in women (OR 3.84, 95% CI 1.82-8.10, P < .0001), and the presence of SH (OR 1.98, 95% CI 1.13-3.46, P = .016) was also an independent risk factor. CONCLUSIONS: Neurotoxicity and SH are the two major adverse effects of polymyxin B in renal transplant patients, which may limit its clinical use.

Outcomes after lung resection in renal transplant patients with pulmonary mucormycosis.

BACKGROUND: Pulmonary mucormycosis has been associated with high mortality (reported up to 100%) in renal transplant recipients. METHODS: This was a retrospective analysis of renal transplant patients with pulmonary mucormycosis between April 2014 and March 2020, who underwent surgical resection of the affected lung along with liposomal amphotericin therapy. Patients with lower respiratory illness features underwent chest X-ray, high-resolution computed tomography of the chest, and those with suspicious findings underwent analysis of bronchioloalveolar fluid and transbronchial lung biopsy. Patients with histological or microbiological evidence of mucormycosis were started on liposomal Amphotericin B. Tacrolimus and mycophenolate mofetil were stopped at the time of diagnosis. RESULT: Ten patients underwent combined management, while five patients were managed medically. At last follow up, seven out of ten patients (70%) who underwent combined management and two of the five patients (40%) who were managed medically, had a mean survival of 28.86 months (sd = 15.71, median = 25) and 14.17 months (sd = 12.21, median = 18), respectively, post-diagnosis of pulmonary mucormycosis. CONCLUSION: Surgical resection combined with antifungals in the perioperative period and decreased immunosuppression may improve the outcomes in renal transplant patients with pulmonary mucormycosis.

Factors associated with telemedicine utilization among post-transplant patients at a university kidney and pancreas transplant center.

INTRODUCTION: Telemedicine has become prevalent during the novel-coronavirus disease-2019 (COVID-19) pandemic. The study explored patient factors associated with telemedicine utilization among post-kidney and pancreas transplant patients at a university center. METHODS AND RESULTS: After analyzing 2801 patients and their visits using chi-square test and logistic regression, we found that government-insured (P < .0001) post-kidney and pancreas transplant patients were less likely to use telemedicine. Sex (P = .748), patient race (P = .920), age groups (P = .812), and traveling distance (P = .837) were not associated with telemedicine use. CONCLUSION: Centers should consider focusing on the subgroup of government-insured patients to improve telemedicine use and future studies should consider exploring barriers for underutilization of telemedicine in this population.

SARS-COV-2 vaccination with BNT162B2 in renal transplant patients: Risk factors for impaired response and immunological implications.

Solid organ transplant patients are at a higher risk for poor CoronaVirus Disease-2019 (COVID-19)-related outcomes and have been included as a priority group in the vaccination strategy worldwide. We assessed the safety and efficacy of a two-dose vaccination cycle with mRNA-based COVID-19 vaccine (BNT162b2) among 82 kidney transplant outpatients followed in our center in Rome, Italy. After a median of 43 post-vaccine days, a SARS-CoV-2 anti-Spike seroprevalence of 52.4% (n = 43/82) was observed. No impact of the vaccination on antibody-mediated rejection or graft function was observed, and no significant safety concerns were reported. Moreover, no de novo HLA-donor-specific antibodies (DSA) were detected during the follow-up period. Only one patient with pre-vaccination HLA-DSA did not experience an increased intensity of the existing HLA-DSA. During the follow-up, only one infection (mild COVID-19) was observed in a patient after receiving the first vaccine dose. According to the multivariable logistic regression analysis, lack of seroconversion after two-dose vaccination independently associated with patient age ≥60 years (OR = 4.50; P = .02) and use of anti-metabolite as an immunosuppressant drug (OR = 5.26; P = .004). Among younger patients not taking anti-metabolites, the seroconversion rate was high (92.9%). Further larger studies are needed to assess the best COVID-19 vaccination strategy in transplanted patients.

Impact of FilmArray™ Respiratory Panel testing on the clinical management of pediatric bone marrow transplant patients.

Viral respiratory tract infections cause significant morbidity in bone marrow transplant (BMT) patients. Speed and sensitivity of the FilmArray™ Respiratory Panel (FA-RP) can improve care but may prompt inappropriate testing. Studies describing FA-RP use in pediatric BMT patients are limited; we investigated FA-RP use, results, and clinical management to evaluate clinical significance of testing in pediatric BMT patients. Retrospective analysis of 671 respiratory specimens from 204 unique BMT patients between 01/01/2016 and 01/01/2019 was performed. Age, underlying diagnoses, FA-RP result, reason for FA-RP, and symptoms were abstracted. FA-RP impact on antimicrobial management, scheduled procedures, infection control measures, and hospital admission/discharge were investigated. Impacts of repeat testing were evaluated. Two hundred sixty-nine out of 671 specimens (40%) tested positive; human rhinovirus/enterovirus (hRV/hEV) was the most common (161/269, 60%). The primary reason for FA-RP was URI symptoms (402/671, 60%) with 54% testing positive. One hundred twenty-two out of 671 (18.2%) specimens were from asymptomatic patients; 14 (11.4%) tested positive. FA-RP informed antiviral initiation in 7/19 (36.8%), 7/8 (87.5%), and 5/30 (16.7%) of RSV, influenza, and human parainfluenza cases, respectively. In 11 cases, FA-RP informed azithromycin and ceftriaxone initiation, continuation, or discontinuation. BMT was delayed for three positives (two RSV, one hRV/hEV). In 22 instances, negative FA-RP cleared patients for BMT. In 70% of cases, repeats offered no new clinical information; all negative-to-positive cases had new or worsening respiratory symptoms. FA-RP was ordered on symptomatic and asymptomatic patients, provided rapid diagnosis in > 50% of symptomatic patients, and informed infection control measures for all inpatients and antiviral initiation in > 80% of influenza cases.

Developing and testing a Corona VaccinE tRiAL pLatform (COVERALL) to study Covid-19 vaccine response in immunocompromised patients.

BACKGROUND: The rapid course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic calls for fast implementation of clinical trials to assess the effects of new treatment and prophylactic interventions. Building trial platforms embedded in existing data infrastructures is an ideal way to address such questions within well-defined subpopulations. METHODS: We developed a trial platform building on the infrastructure of two established national cohort studies: the Swiss human immunodeficiency virus (HIV) Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS). In a pilot trial, termed Corona VaccinE tRiAL pLatform (COVERALL), we assessed the vaccine efficacy of the first two licensed SARS-CoV-2 vaccines in Switzerland and the functionality of the trial platform. RESULTS: Using Research Electronic Data Capture (REDCap), we developed a trial platform integrating the infrastructure of the SHCS and STCS. An algorithm identifying eligible patients, as well as baseline data transfer ensured a fast inclusion procedure for eligible patients. We implemented convenient re-directions between the different data entry systems to ensure intuitive data entry for the participating study personnel. The trial platform, including a randomization algorithm ensuring balance among different subgroups, was continuously adapted to changing guidelines concerning vaccination policies. We were able to randomize and vaccinate the first trial participant the same day we received ethics approval. Time to enroll and randomize our target sample size of 380 patients was 22 days. CONCLUSION: Taking the best of each system, we were able to flag eligible patients, transfer patient information automatically, randomize and enroll the patients in an easy workflow, decreasing the administrative burden usually associated with a trial of this size.

Molecular characterization of BK virus detected in renal transplant patients in Sri Lanka: a preliminary study.

Background & objectives: BK virus (BKV) is a polyomavirus and cause of a common infection after renal transplantation which could be preceded to BKV-associated nephropathy. It has four main subtypes (I-IV). BKV subtypes II and III are rare, whereas subtype I shows a ubiquitous distribution. The objective of the present study was to investigate the prevailing BKV subtypes and subgroups in renal transplant patients in Sri Lanka. Methods: The presence of BKV in urine was tested through virus load quantification by real-time PCR from 227 renal transplant patients who were suspected to have BKV infection. Of these patients only 41 were found to be BKV infected (>103 copies/ml) and those were subjected to conventional PCR amplification of VP1 gene followed by BKV genotyping via phylogenetic analysis based on DNA sequencing data. Results: Persistent BK viral loads varied from 1×103 to 3×108 copies/ml. Of the 41 patient samples, 25 gave positive results for PCR amplification of subtyping region of VP1 gene of BKV. BKV genotyping resulted in detecting subtype I in 18 (72%) and subtype II in seven (28%) patients. BKV subgroups of Ia, Ib-1 and Ib-11, and Ic were identified with frequencies of 6/18 (33.3%), 6/18 (33.3%), 5/18 (27.8%), and 1/18 (5.6%), respectively. Interpretation & conclusions: Findings from this preliminary study showed a high occurrence of subtype I, while the presence of subtype II, which is rare and less prevalent, was a novel finding for this Asian region. This emphasizes the need for further molecular and serological studies to determine the prevalence of different BKV subtypes in Sri Lanka.

Emergomyces orientalis Emergomycosis Diagnosed by Metagenomic Next-Generation Sequencing.

Emergomyces is a newly described dimorphic fungus genus; it may cause fatal infections in immunocompromised patients, but diagnosis is often delayed. We report a case of disseminated emergomycosis caused by the novel species Emergomyces orientalis in a kidney transplant recipient from Tibet. Infection was diagnosed early by metagenomic next-generation sequencing.

Molecular identification of Acanthamoeba genotypes isolated from oral cavity of heart transplant patients in Iran.

OBJECTIVE: Heart transplant is one of the accepted treatments for some patients with advanced heart failure. Of note, transplant surgeries may cause different infections and complications for patients during the post-transplant period. A wide variety of opportunistic organisms caused these infections including bacteria, fungi, viruses, and protozoa particularly Free-living amoebae (FLA). This study aims to study the presence of pathogenic FLA from the oral cavity of post-heart transplant recipients. METHODS: Throat swabs were collected from 80 patients who underwent post-heart transplant surgery. All swabs were immediately cultured in non-nutrient agar (2%). PCR and sequencing of 18S rRNA gene (DF3 region) of Acanthamoeba isolates were performed using genus-specific primers. Genetic associations among sequenced genotypes inferred by the 18S rRNA gene obtained by MEGA X and a phylogenetic tree were constructed using the maximum likelihood algorithm and Kimura 2-parameter model. RESULTS: Out of 80 samples collected from post-heart transplant patients, six (7.5%) samples showed positive outgrowth of Acanthamoeba based on the page key and sequencing of the DF3 region. Sequence similarity of ASA1 by basic local alignment search tool(n) showed that five isolates (ANHT1, ANHT2, ANHT3, ANHT4, and ANHT5) belonged to Acanthamoeba T5 genotype corresponding to A. lenticulata and one strain (ANHT6) belonged to the T4 genotype. CONCLUSION: To the best of our knowledge for the first time, a comprehensive study of Acanthamoeba genotypes isolated from throat samples of heart transplant recipients is described. Heart transplantation patients can be colonized by FLA and are therefore at risk of developing an invasive infection. Physicians' awareness of central nervous system infections related to FLAs and preventive and control measures of patients with compromised immune status due to heart transplant surgery are of utmost importance.

Preoperative autologous blood donation for kidney transplant and end-stage renal disease patients: A single-center study.

Although preoperative autologous blood donation (PABD) has many advantages, there has been a decrease in the performance due to a decrease in the residual risk of allogeneic blood transfusion. In allogeneic blood transfusion, anti HLA antibodies and donor-specific antibodies mediate antibody-mediated rejection, which results in graft failure. PABD for anemic patients such as those with end-stage renal disease (ESRD) and a kidney transplant is relatively contraindicated. In this study, we aimed to investigate the characteristics of patients who underwent PABD and elucidate the safety and feasibility of PABD. We performed PABD safely in ten ESRD patients and nine kidney transplant patients and retrospectively analyzed medical records of the hospital. All kidney transplant patients avoided allogeneic blood transfusion, but 4 out of 10 ESRD patients had allogeneic blood transfusion, even if their blood donation volume was larger than those of the kidney transplant patients. It depends on the type of operation; cardiovascular surgery was more common in ESRD patients, and orthopedic surgery was more common in kidney transplant patients. There was profuse bleeding in cardiovascular surgery compared to orthopedic surgery because of longer operation time of the former. Completely avoiding allogeneic blood transfusion in major surgery was rather difficult even if PABD was performed. To prevent the formation of anti- HLA antibodies, PABD would be considered for ESRD patients undergoing kidney transplantation and kidney transplant patients that are potential candidates for secondary kidney transplantation.

Safety and effectiveness of everolimus in maintenance kidney transplant patients in the real-world setting: results from a 2-year post-marketing surveillance study in Japan.

BACKGROUND: Data on real-world use of everolimus (EVR) in Japanese maintenance kidney transplant (KTx) patients are limited. This post-marketing surveillance study was conducted to assess the safety and effectiveness of EVR, and identify factors affecting renal impairment. METHODS: Adult maintenance KTx patients were enrolled within 14 days of initiating EVR. Patient medical data were collected using electronic data capture case report forms at 6 months, 1, and 2 years after initiating EVR, or at discontinuation. RESULTS: All patients receiving EVR in Japan during the surveillance period were enrolled (N = 263). Mean time from transplantation to EVR initiation was 75.7 months. Decreased renal function (31.56%) was the primary reason for initiating EVR. In combination with EVR, the mean daily dose of tacrolimus and cyclosporine could be reduced to ~ 79 and ~ 64%, by 2 years, respectively. Incidences of serious adverse events and adverse drug reactions were 15.97 and 49.43%, respectively. Two-year graft survival rate was 95.82% and low in patients with baseline estimated glomerular filtration rate (eGFR; modification of diet in renal disease) < 30 mL/min/1.73 m2 (69.57%; P < 0.0001) and urinary protein/creatinine ratio (UPCR) ≥ 0.55 g/gCr (84.21%; P = 0.0206). Throughout the survey, mean eGFR values were stable (> 55 mL/min/1.73 m2). Renal impairment was influenced by patient and donor age, eGFR, and UPCR at baseline. CONCLUSIONS: No new safety concerns for the use of EVR in adult maintenance KTx patients were identified. Early EVR initiation may be considered in these patients before renal function deterioration occurs.

Assessment of pharmacokinetic mycophenolic acid clearance models using Monte Carlo numerical analysis.

Previously, we performed population pharmacokinetic analysis and indicated age, mycophenolate mofetil (MMF)/mycophenolic acid (MPA) daily dose, and presence of nifedipine in patient therapy as significant predictors of MPA apparent clearance (CL/F) variability. This study aimed to determine the reliability of previously published population pharmacokinetic models derived from similar studies. Furthermore, this study investigated correspondence between chosen population models from the literature.By means of the Monte Carlo simulation method, pharmacokinetic models from different studies are simulated and analysed in the range of standard deviations of measured system parameters as well as the range of observed model parameters taken from the comparison studies.The 1000 numerical simulations were performed for every analysed model in order to calculate the most possible MPA CL/F values according to the expected values from the performed experiment. Fitting our results with other models showed how the presence of nifedipine makes difference in MPA CL/F values.By testing the data from selected studies into our model, a similar range of expected CL/F values was obtained, which may confirm the validity of our model. The results of our population pharmacokinetic study are partially applicable in models by other researchers.