An Innovative Approach to Assessing the Psychosocial Impacts on Liver Transplant Recipients: The Prediction-by-correspondence Analysis.

Background: Innovative analytic techniques are applied to the psychological functioning of liver transplant (LT) recipients to comprehend its effect on post-transplant survival, hypothesizing that adherence will be predicted by psychosocial functioning. Methods: The psychosocial functioning of 248 LT recipients (88 females) aged 19 to 74 is assessed using the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT). In addition, the Medication Level Variability Index (MLVI) and biopsy-proven rejection are utilized to evaluate successful adherence. The Z-scores of the SIPAT scores are used to transform them into an ordinal variable with excellent, good, minimally acceptable, and poor categories. We employ a modified version of correspondence analysis to predict the binary MLVI and rejection, which signify either success or failure in adherence, using ordinal MLVI categories as predictors. Results: The excellent SIPAT category for LT beneficiaries was strongly related to adherence, whereas the minimally acceptable SIPAT was strongly related with failure in adherence. Females, ages 19-50, and ages 67-74 were associated with adherence (r = 0.49-1.00), whereas males and ages 56-60 were associated with failure in adherence (r = 0.43-0.91). Conclusion: The clinical implications and utility of the novel analytic approaches introduced in the study are discussed.

HLA Awareness in tissue decellularization: A paradigm shift for enhanced biocompatibility, studied on the model of the human fascia lata graft.

Last twenties, tissue engineering has rapidly advanced to address the shortage of organ donors. Decellularization techniques have been developed to mitigate immune rejection and alloresponse in transplantation. However, a clear definition of effective decellularization remains elusive. This study compares various decellularization protocols using the human fascia lata model. Morphological, structural and cytotoxicity/viability analyses indicated that all the five tested protocols were equivalent and met Crapo's criteria for successful decellularization. Interestingly, only the in vivo immunization test on rats revealed differences. Only one protocol exhibited Human Leucocyte Antigen (HLA) content below 1% residual threshold, the only criterion preventing rat immunization with an absence of rat anti-human IgG switch after one month (N=4 donors for each of the 7 groups, added by negative and positive controls, n=28). By respecting a refined set of criteria, i.e. lack of visible nuclear material, <50ng DNA/mg dry weight of extracellular matrix, and <1% residual HLA content, the potential for adverse host reactions can be drastically reduced. In conclusion, this study emphasizes the importance of considering not only nuclear components but also major histocompatibility complex in decellularization protocols and proposes new guidelines to promote safer clinical development and use of bioengineered scaffolds.

Outcome of Solid Organ Transplantation in Patients With Intellectual Disability: A Systematic Literature Review.

Access to solid organ transplantation in patients with intellectual disability is associated with health inequities due to concerns about treatment adherence, survival rates, and post-transplant quality of life. This systematic literature review aims to compare outcomes after organ transplantation in patients with intellectual disability compared to patients without intellectual disability. Embase, Medline Ovid, PsycINFO, Web of Science, Cochrane Central Register of Trials, and Google Scholar databases were systematically searched for studies concerning pediatric or adult solid organ transplantation in recipients with a diagnosis of intellectual disability prior to transplantation. Primary outcomes were patient and graft survival rates. Secondary outcomes were acute rejection rate, adherence rates, and quality of life. Nine studies were included, describing kidney (n = 6), heart (n = 4) and liver (n = 1) transplantation. Reported graft survival rates were non-inferior or better compared to patients without intellectual disability, while patient survival was reportedly slightly lower in two studies reporting on kidney transplantation. Although current evidence has a potential selection bias based on including patients with a sufficient support network, intellectual disability alone should not be regarded a relative or absolute contra-indication for solid organ transplantation.

Miniaturized broadband high out-of-band rejection bandpass filter based on spoof surface plasmon polaritons with defected ground structure.

In this paper, a novel compact bandpass filter (BPF) with a wide out-of-band rejection is proposed. It can achieve broadband characteristics by combining hollow bowtie-type spoof surface plasmon polaritons (SSPPs) with complementary H-type defected grounded structures (DGSs) through aperture coupling. Compared with the conventional SSPP unit cells, the hollow bowtie-type structure exhibits much better slow-wave characteristics. The introduced slant antenna type port-coupling can produce a very strong high-performance rejection outside the high frequency stopband. Simulation results show that the SSPPs-DGS-based BPF has an excellent band pass characteristics in a broadband range with - 3dB fractional bandwidth of 43.5% at center frequency f0 of 2.04 GHz. The return loss in the passband is better than - 12 dB. Furthermore, because of the multiple transmission zeros generated in upper-stop-band, the designed BPF has an extremely strong out-of-band rejection of -40dB from 1.5 f0 to 4 f0 (f0 is the center frequency). The designed SSPPs-DGS-based BPF is fabricated by conventional printed circuit board (PCB) technology with a compact size of only 0.68λg*0.34λg (λg is the wavelength at the center frequency). The measured results have a good agreement with the simulation ones, which verifies the rationality and feasibility of the design. The miniaturized wideband BPF with broad out-of-band rejection may make it has good application prospect in the new generation microwave communication field.

Langerhans Cell Histiocytosis or Acute Cellular Rejection?

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare malignant disorder of epidermal antigen presenting cells. It is characterized by infiltration of various tissues with dendritic cells (Langerhans cells, LC) that express CD1a or CD207 (langerin), often leading to organ dysfunction. A patient with LCH required liver transplantation (LT) for LCH-associated biliary-tract disease. Cholangiopathy developed after LT. The question arose: In this patient, did LC in damaged liver-allograft biliary epithelium signify acute cellular rejection (ACR) or recurrent LCH? METHODS: We evaluated immunohistochemical identification of LC (CD1a, CD207) in the proposita and in 14 ACR patient samples as distinguishing between ACR and recurrent LCH. RESULTS: Among 15 patient samples, 3 (20%) marked with neither antibody. Among the remaining 12 samples (80%), 4 (26.7%)-including that from the proposita-had cells marking for both antigens within bile-duct epithelium as well as in surrounding portal-tract connective tissue, 2 (13.3%) had cells marking for both antigens in one region or the other, but not in both, and 6 (40%) had cells marking for only one antigen in one region or the other. CONCLUSIONS: Immunostaining for CD1a and CD207/langerin in the setting of ACR without suspicion of LCH identifies LC in damaged bile ducts. This biomarker pairing proved not to be LCH-specific. Our findings indicate that the presence of these cells alone is insufficient to identify recurrent LCH in the allograft liver.

A machine learning based framework to tailor properties of nanofiltration and reverse osmosis membranes for targeted removal of organic micropollutants.

Nanofiltration (NF) and reverse osmosis (RO) membranes play an increasingly important role in the removal of organic micropollutants (OMPs), which puts higher demands on the customization of membranes suitable for OMPs removal based on the rejection mechanisms. Here, the pathways of OMPs-targeted optimization for membranes were constructed by using machine learning (ML) to capture the correlations between OMPs removal efficiency with properties of membranes and OMPs. Through expertise assistance and rigorous modeling methodology, an accurate and robust Extreme Gradient Boosting (XGBoost) model was established, which could well recognize the dominant rejection mechanisms of OMPs (i.e., the size exclusion effect and electrostatic interactions). An exemplary application to another dataset of several high-risk OMPs showed how the optimized model could be used to estimate the overall efficiency of OMPs risk control and, more importantly, to provide quantitative guidance on membrane properties for specific removal targets. The satisfying prediction results demonstrated the good generalization of the ML model and consequently its ability to sensitively define the ideal membrane properties for the targeted removal of these (and any other concerned) OMPs. This study provides a feasible and universal ML-based framework to achieve the tailored selection and design of NF/RO membranes for OMPs risk control.

Self-assembled sub-picoliter liquid periodic structures in a hollow optical fiber.

In an experimental exploration, we successfully implemented a self-assembling methodology to construct a periodic liquid-air structure inside a hollow optical fiber (HOF). This fiber comprises a central air hole, a germanosilica ring core, and a silica cladding. A periodic structure of liquid droplets and air was obtained by the application of a microscopic heat source (MHS) traversing along the axial direction of the liquid-filled HOF. In the course of this study, we discerned three distinct zones within the structure. The first zone, referred to as Zone 1, demonstrated near-constant periodicity. The second zone, Zone 2, exhibited adaptable properties with regard to its periodicity, allowing it to be flexibly controlled. In the third zone, Zone 3, we noticed a chaotic response to external parameters, including temperature and the speed at which MHS was traversed. To regulate the liquid-air periodic structures, two different types of MHSs were utilized - a micro hydro-oxygen torch and a metal ring heater, each mounted on a translation stage. The study provides a detailed account of the parameters employed in utilizing these MHSs. Additionally, the optical properties of these liquid-air periodic structures were meticulously analyzed to explore the potential for developing new optofluidic applications.

Successful use of therapeutic plasma exchange for the management of acute lung transplant rejection secondary to immune checkpoint inhibitor therapy.

The use of immune checkpoint inhibitors (ICIs) in individuals with a history of solid organ transplantation is fraught with the emergence of solid organ transplantation rejection (SOTR). The current recommendations for the management of SOTRs secondary to ICI include the use of high-dose steroids along with the escalation of immunosuppressive therapy. Therapeutic Plasma Exchange (TPE) has been described to be effective in managing various immune-related toxicities, however, the data for using TPE in the setting of acute SOTRs induced by ICIs are limited. Herein, we describe the successful use of TPE in a patient with a history of bilateral lung transplantation who developed an episode of mixed acute cellular and antibody-mediated lung transplant rejection after a single dose of PD-1 inhibitor Pembrolizumab for the treatment of underlying melanoma.

Oxymatrine Attenuates Chronic Allograft Rejection by Modulating Immune Responses and Inhibiting Fibrosis.

BACKGROUND: Chronic rejection (CR) is a significant obstacle to long-term allograft survival. Oxymatrine (OMT) is a prominent bioactive compound widely utilized in traditional Chinese medicine for the management of inflammatory disorders and it has considerable potential as a therapeutic candidate for the treatment of CR. METHODS: Well-established major histocompatibility complex (MHC) class II mismatched B6 mice. C-H-2bm12-to-C57BL/6 mouse transplantation was used as a CR model. Hematoxylin and eosin (H&E) staining, immunohistochemistry, and Masson's trichrome staining were used to assess pathological changes in the grafts, and the percentages of immune cells were determined by flow cytometry. The effects of OMT on the regulation of CD4+ T cell differentiation and cytokine secretion were verified in vitro. RESULTS: OMT effectively alleviated pathological graft damage, characterized by chronic changes in intimal lesions, vasculopathy, and fibrosis and significantly prolonged cardiac allograft survival. OMT exerted its immunomodulatory effects by inhibiting T helper 1 (Th1) and T helper 17 (Th17) cell differentiation while promoting Treg differentiation both in vivo and in vitro. Further studies revealed that OMT inhibited the phosphorylation of mammalian target of rapamycin (mTOR), which is a potential mechanism underlying its immunosuppressive effects. OMT also inhibited the activation of B cells and the production of donor-specific antibody (DSA). In addition, OMT effectively alleviated chronic changes in fibrosis in cardiac allografts, and these changes may be related to the inhibition of the transforming growth factor-ß (TGF-ß)-Smad 2/3 pathway. CONCLUSIONS: OMT attenuated CR by modulating the immune response and inhibiting graft fibrosis. Further in-depth investigations of OMT may provide valuable insights into the development of novel therapeutic strategies for CR inhibition.

Evaluation of Single Versus Two-Dose Basiliximab Induction Therapy in Live-Donor Liver Transplant.

BACKGROUND: Basiliximab is a high-cost induction agent typically given as two doses in liver transplant recipients. This study evaluated renal outcomes in live-donor liver transplant recipients (LDLTRs) with stable renal function at the time of transplant receiving one versus two doses of basiliximab. METHODS: We retrospectively identified 231 adult LDLTR with a serum creatinine (SCr) <1.5 mg/dL on post-transplant Day 5. The primary endpoint was a change in SCr from post-transplant Days 5 to 30 between the groups. Secondary endpoints included incidence of acute kidney injury (AKI), liver rejection, and culture-positive infections within 3 and 6 months of transplant. Basiliximab-related cost savings were also evaluated. RESULTS: Median change in SCr from post-transplant Days 5 to 30 was no different between the single-dose or two-dose groups (0.1 [IQR: -0.1-0.3] vs. 0.2 [IQR: -0.1-0.4], p = 0.08). Incidence of AKI was 56.9% in the two-dose group versus 39.0% in the single-dose group (p = 0.01). There was no difference in bacterial (p = 0.40), fungal (p = 0.59), or viral (p = 0.78) infections. Acute cellular rejection through 6 months post-transplant was noted in 9.7% of patients receiving two doses and 6.3% in the single-dose arm (p = 0.42). Basiliximab-related cost savings in the single-dose arm was ∼$697 863.72 over 159 transplants. CONCLUSIONS: Single-dose basiliximab appears to be safe and effective in place of two doses in LDLTR with stable renal function on post-transplant Day 5. Utilization of a single basiliximab dose significantly reduced medication-related costs.

Acute Allograft Rejection in Kidney Transplant Recipients Treated With Immune Checkpoint Inhibitors: An Educational Case Report.

Rationale: Kidney transplant (KT) recipients have an increased risk of malignancy due to chronic immunosuppression. The emerging use of immune checkpoint inhibitors (ICIs) has been a promising development for the treatment of malignancy, but their use adds to the complexity of immunosuppression management for KT recipients. This case report describes 2 cases of acute rejection in KT recipients following ICI initiation and discusses the balance of malignancy treatment with adequate immunosuppression. Presenting Concerns of Patients: The first patient is a 44-year-old male KT recipient with a diagnosis of metastatic renal cell carcinoma presenting with acute kidney injury 6 days following initiation of an ICI. The second patient is a 73-year-old male KT recipient with a diagnosis of squamous cell carcinoma presenting with acute kidney injury 2 weeks following initiation of an ICI. Diagnoses: Both patients were diagnosed with acute rejection in the setting of reduced immunosuppression and initiation of an ICI. Interventions: Both cases received an increased dose of steroid without improvement of graft function. The first patient subsequently underwent a delayed graft nephrectomy due to complications of acute rejection, whereas the second patient did not undergo nephrectomy. Outcomes: The first patient experienced complications including perioperative bleeding requiring multiple operations, but ultimately stabilized on hemodialysis and showed a durable response to ICI. The second patient remained dialysis-dependent post-ICI treatment and was readmitted with allograft complications leading to his eventual death. Teaching Points: This study underscores the complexity of managing KT recipients diagnosed with malignancy and receiving ICIs. The balance between immunosuppression reduction to treat malignancy and preventing allograft rejection presents a significant challenge. Key considerations include the risk of acute allograft rejection and patient-centered decision-making. These cases highlight the need for further research to develop evidence-based guidelines for managing this patient population. In addition, the patient perspective in this study highlights the importance of careful risk-benefit analysis and the impact of treatment decisions on patient-focused outcomes.

Contexte: Les receveurs d'une greffe rénale (RGR) présentent un risque accru de cancer en raison de l'immunosuppression chronique. L'utilisation émergente des inhibiteurs du point de contrôle immunitaire (IPCI) s'est avérée un développement prometteur pour traiter les cancers, mais elle ajoute à la complexité de la gestion de l'immunosuppression chez les RGR. Cette étude décrit deux cas de rejet aigu chez des RGR après l'initiation des IPCI et discute du difficile équilibre entre le traitement du cancer et une immunosuppression adéquate. Présentation des cas: Le premier patient est un homme de 44 ans ayant reçu un diagnostic de carcinome à cellules rénales métastatique qui a présenté une insuffisance rénale aiguë six jours après l'initiation des IPCI. Le second patient est un homme de 73 ans ayant reçu un diagnostic de carcinome épidermoïde qui a présenté une insuffisance rénale aiguë deux semaines après l'initiation des IPCI. Diagnostic: Dans les deux cas, le rejet aigu a été diagnostiqué à la suite de la réduction de l'immunosuppression et de l'initiation des IPCI. Intervention: Les deux patients ont reçu une dose plus élevée de stéroïdes sans amélioration de la fonction du greffon. Le premier patient a subi une néphrectomie retardée du greffon en raison de complications de rejet aigu, ce qui n'a pas été le second patient. Résultats: Le premier patient a subi des complications, notamment des saignements périopératoires qui ont nécessité de multiples opérations, mais s'est finalement stabilisé avec l'hémodialyse et a montré une réponse durable aux IPCI. Le second patient est demeuré sous dialyse après le traitement aux IPCI et a été réadmis avec des complications de l'allogreffe qui ont entraîné son décès. Enseignements tirés: Cette étude souligne la complexité de la prise en charge des RGR qui reçoivent un diagnostic de tumeur maligne et des traitements par IPCI. L'équilibre entre la réduction de l'immunosuppression pour traiter le cancer et la prévention du rejet de l'allogreffe constitue un important défi. Le risque de rejet aigu de l'allogreffe et la prise de décision centrée sur le patient sont des éléments clés à prendre en compte. Ces deux cas soulignent la nécessité de poursuivre les recherches afin d'élaborer des lignes directrices fondées sur des données probantes pour la gestion de cette population de patients. De plus, le point de vue du patient dans cette étude met en évidence l'importance d'analyser rigoureusement le rapport risques-bénéfices et l'impact des décisions de traitement sur les résultats axés sur le patient.

Peptide Sharing Between CMV and Mismatched HLA Class I Peptides Promotes Early T-Cell-Mediated Rejection After Kidney Transplantation.

Cytomegalovirus (CMV) infection is related to acute rejection and graft loss after kidney transplantation, though the underlying mechanism remains largely unknown. Some CMV strains produce a peptide that is identical to a peptide sequence found in the leader peptide of specific HLA-A and -C alleles. In this retrospective study of 351 kidney transplantations, we explored whether CMV-seropositive recipients without the VMAPRTLIL, VMAPRTLLL or VMAPRTLVL HLA class I leader peptide receiving a transplant from a donor with this peptide, faced an increased risk of T-cell-mediated rejection (TCMR) in the first 90 days after transplantation. An independent case-control cohort was used for validation (n = 122). The combination of recipient CMV seropositivity with the VMAPRTLIL peptide mismatch was associated with TCMR with a hazard ratio (HR) of 3.06 (p = 0.001) in a multivariable analysis. Similarly, the VMAPRTLLL peptide mismatch was associated with TCMR revealing a HR of 2.61 (p = 0.008). Transplantations featuring either a VMAPRTLIL or a VMAPRTLLL peptide mismatch had a significantly higher cumulative TCMR incidence (p < 0.0001), with the primary impact observed in the first 2 weeks post-transplantation. The findings could be validated in an independent cohort. Together, our data strongly suggest that CMV-positive recipients without an HLA peptide identical to a CMV peptide yet transplanted with a donor who does possess this peptide, have a significantly increased risk of early TCMR. Considering the prevention of such an leader peptide mismatch in these patients or adjusting immunosuppression protocols accordingly may hold promise in reducing the incidence of early TCMR.

Molecular landscape of kidney allograft tissues data integration portal (NephroDIP): a curated database to improve integration of high-throughput kidney transplant datasets.

Introduction: Kidney transplantation is the optimal treatment for end-stage kidney disease; however, premature allograft loss remains a serious issue. While many high-throughput omics studies have analyzed patient allograft biospecimens, integration of these datasets is challenging, which represents a considerable barrier to advancing our understanding of the mechanisms of allograft loss. Methods: To facilitate integration, we have created a curated database containing all open-access high-throughput datasets from human kidney transplant studies, termed NephroDIP (Nephrology Data Integration Portal). PubMed was searched for high-throughput transcriptomic, proteomic, single nucleotide variant, metabolomic, and epigenomic studies in kidney transplantation, which yielded 9,964 studies. Results: From these, 134 studies with available data detailing 260 comparisons and 83,262 molecules were included in NephroDIP v1.0. To illustrate the capabilities of NephroDIP, we have used the database to identify common gene, protein, and microRNA networks that are disrupted in patients with chronic antibody-mediated rejection, the most important cause of late allograft loss. We have also explored the role of an immunomodulatory protein galectin-1 (LGALS1), along with its interactors and transcriptional regulators, in kidney allograft injury. We highlight the pathways enriched among LGALS1 interactors and transcriptional regulators in kidney fibrosis and during immunosuppression. Discussion: NephroDIP is an open access data portal that facilitates data visualization and will help provide new insights into existing kidney transplant data through integration of distinct studies and modules (https://ophid.utoronto.ca/NephroDIP).

Biomarkers of Rejection in Kidney Transplantation.

Alloimmune injury is a major cause of long-term kidney allograft failure whether due to functionally stable (subclinical) or overt clinical rejection. These episodes may be mediated by immune cells (cellular rejection) or alloantibody (antibody-mediated rejection). Early recognition of immune injury is needed for timely appropriate intervention to maintain graft functional viability. However, the conventional measure of kidney function (i.e., serum creatinine) is insufficient for immune monitoring due to limited sensitivity and specificity for rejection. As a result, there is need for biomarkers that more sensitively detect the immune response to the kidney allograft. Recently, several biomarkers have been clinically implemented into the care of kidney transplant recipients. These biomarkers attempt to achieve multiple goals including (1) more sensitive detection of clinical and subclinical rejection, (2) predicting impending rejection, (3) monitoring for the adequacy of treatment response, and (4) facilitating personalized immunosuppression. In this review, we summarize the findings to date in commercially available biomarkers, along with biomarkers approaching clinical implementation. While we discuss the analytical and clinical validity of these biomarkers, we identify the challenges and limitations to widespread biomarker use, including the need for biomarker-guided prospective studies to establish evidence of clinical utility of these new assays.

Preparation and evaluation of novel oral tacrolimus nanocochleates for organ transplantation to reduce individual differences and improve drug safety.

After organ transplantation, patients require treatment with immunosuppressive drugs to prevent immune rejection and transplantation failure. Tacrolimus (FK506) is a widely used immunosuppressant known for its potent immunosuppressive effect and narrow therapeutic range. Monitoring of FK506 blood concentrations is essential to avoid nephrotoxicity. In this study, a novel FK506 nanomedicine (FK506 cochleates) was developed using a microfluidic method to reduce variability among individuals and improve drug safety. The particle size of FK506 cochleates was (183.3 ± 1.4) nm, the zeta potential was -(39.28 ± 2.12) mV, and the encapsulation efficiency was more than 85 %. Particle size of FK506 cochleates could be maintained for up to 12 weeks in freeze-dried powder form. Small-angle X-ray scattering (SAXS) experiment confirmed the formation of cochleates by adding calcium solution. In vitro release studies demonstrated a sustained-release profile of FK506 from the cochleates carrier. Furthermore, the cochleates carrier could protect FK506 from the influence of stomach acid and slowly release the drug in the intestine. After oral administration, FK506 cochleates exhibited sustained-release properties in rats, accumulating in the spleen and lymph nodes - key anatomical sites for FK506's pharmacological action. Importantly, FK506 cochleates significantly prolonged the survival time in the rabbit heart transplantation model while maintaining good safety profiles. In conclusion, the FK506 cochleates showed promising potential for enhancing drug safety in therapeutic organ transplantation.

Burn injury and fear of rejection: A qualitative study.

INTRODUCTION: One of the most important duties of the members of the treatment team is to pay attention to the mental, psychological, and social aspects of burn patients. One of the concerns of these patients during their stay in the hospital is the fear of rejection. The objective of this research is to examine the concept of 'fear of rejection' among patients hospitalized with burn injuries. METHOD: This study was conducted between January 2023 and March 2024 in Hamadan, Iran, employing a qualitative content-analysis approach. The study enrolled sixteen patients, and data were collected through deep and semi-structured interviews. The data were then analyzed using the conventional content-analysis approach developed by Graneheim and Lundman. RESULTS: A group of 16 patients, comprising an equal number of men and women, were interviewed for this study. Based on the data obtained from these interviews, negative brainstorming, frustration, fear of permanent physical disabilities, occupational and financial challenges were identified as categories; visualization of a foggy future and inability in performance of roles emerged as the two themes. CONCLUSION: Based on the results of this study, it can be said that the fear of social rejection, characterized by an inability to perform roles and the visualization of a foggy future, significantly affects the psychological and physical health of burn patients, potentially delaying their recovery. Assisting these patients in reaching their fullest potential to contribute to society post-discharge, and fostering optimism for a promising future, constitute a paramount aspect of daily care and ongoing support.

Ultra-Wideband Common-Mode Rejection Structure with Autonomous Phase Balancing for Ultra-High-Speed Digital Transmission.

For ultra-high-speed digital transmission, required by 5G/6G communications, ultra-wideband common-mode rejection (CMR) structures with autonomous phase-balancing capability are proposed. Common-mode noise, caused by phase and amplitude unbalances, is one of the most undesired disturbances affecting modern digital circuits. According to the circuit design guides with a typically used differential line (DL) for high-speed digital transmission, common-mode rejection is achieved using CMR filters, and the unbalanced phase, caused by a length difference between the two signal lines of a DL, is compensated by inserting an additional delay line. However, due to nonlinear phase interactions between the two DLs and unbalanced electromagnetic (EM) interferences, the conventional compensation method is frequency-limited at around 10 GHz. To significantly enhance the common-mode rejection level and extend the phase recovery bandwidth, the proposed CMR structure utilizes a planar balanced line (BL), such as a coplanar stripline (CPS) or a parallel stripline (PSL), along with additional conductor strips arranged laterally near the BL. To demonstrate the performance of the proposed BL-based CMR structures, various types of CMR structures are fabricated, and the measurement results are compared with the 3D EM simulation results. As a result, it is proven that the proposed BL-based CMR structures have the capability to reject the common-mode noise with suppression levels of more than 10 dB and to simultaneously recover the phase balance from near DC to over 40 GHz.

Early CYP3A5 Genotype-Based Adjustment of Tacrolimus Dosage Reduces Risk of De Novo Donor-Specific HLA Antibodies and Rejection among CYP3A5-Expressing Renal Transplant Patients.

BACKGROUND/OBJECTIVES: Our previous retrospective single-center cohort study found, at 3-year follow-up, a trend toward low tacrolimus trough levels and an increased risk of de novo donor-specific anti-HLA antibodies (DSAs) and of antibody-mediated rejection (ABMR) in CYP3A5-expressing patients. Determining CYP3A5-expression status immediately after renal transplant would allow early genotype-based dosage adjustment of tacrolimus and might prevent the occurrence of de novo DSAs and ABMR, improving transplant outcome. METHODS: 160 renal allograft recipients who underwent renal transplant at the University Hospital Essen between May 2019 and May 2022 were genotyped for the CYP3A5 rs776746 polymorphism within the first two weeks after transplant, and genotype-based dose adjustment of tacrolimus was performed for the follow-up of 2 years. RESULTS: CYP3A5 expression was detected in 33 (21%) of the 160 patients. Tacrolimus trough levels were similar in CYP3A5 expressers and nonexpressers over the entire 2-year follow-up period. However, we observed a trend toward slightly higher tacrolimus trough levels in CYP3A5 expressers, who, as expected, required tacrolimus dosages twice as high as did nonexpressers during follow-up. Calcineurin inhibitor (CNI) nephrotoxicity-free survival rates were comparable between CYP3A5 expressers and nonexpressers (p = 0.49). Rejection-free survival rates (p = 0.89), de novo anti-HLA antibody-free survival rates (p = 0.57) and de novo DSA-free survival rates (p = 0.61) did not differ between the two groups. CONCLUSIONS: Early detection of CYP3A5-expression status and resultant genotype-based adjustment of tacrolimus dosage after renal transplant protected patients from transplant rejection and de novo DSA formation and was not associated with increased incidence of CNI toxicity among CYP3A5 expressers.