Intestinal ultrasound may be a useful tool in monitoring acute rejection following intestinal transplantation.

BACKGROUND: Acute rejection is the leading cause of mortality and morbidity for children following intestinal transplantation. Rapid detection and prompt treatment are critical; however, the only reliable method of diagnosis and monitoring is endoscopic graft biopsies. The required regular anesthetics are particularly problematic in children, and non-invasive strategies are needed. METHODS: We describe the intestinal ultrasound findings of three children before and after treatment for rejection. Ultrasounds were performed within 24 h of endoscopically obtained biopsies which were used to establish a diagnosis of rejection and to define severity. A single sonographer performed the ultrasounds and was blinded to biopsy results at the time of the scanning. These findings are provided in the context of the ultrasound appearance of seven children who had no features of rejection on surveillance biopsies. RESULTS: Intestinal ultrasound demonstrated increased bowel wall thickness, vascularity, and mesenteric inflammation during moderate to severe rejection episodes. The submucosal layer was particularly thickened, which may represent a finding more specific for rejection. All patients demonstrated improvement in all quantitative ultrasound features correlating with the resolution of acute cellular rejection on histology. Patients with no evidence of rejection on biopsy had a bowel wall thickness range of 0.9-2.8 mm, suggesting a normal upper limit of 3 mm. CONCLUSION: Moderate and severe acute rejection may be detected and response to treatment can be monitored by intestinal ultrasound and, correlating with clinical improvement, can aid in follow-up.

A Novel Three-Dimensional Approach Towards Evaluating Endomyocardial Biopsies for Follow-Up After Heart Transplantation: X-Ray Phase Contrast Imaging and Its Agreement With Classical Histopathology.

Endomyocardial biopsies are the gold standard for surveillance of graft rejection following heart transplantation, and are assessed by classical histopathology using a limited number of previously stained slices from several biopsies. Synchrotron propagation-based X-ray phase contrast imaging is a non-destructive method to image biological samples without tissue preparation, enabling virtual 2D and 3D histopathology. We aimed to show the feasibility of this method to assess acute cellular rejection and its agreement to classical histopathology. Right ventricular biopsies were sampled from 23 heart transplantation recipients (20 males, mean age 54±14 years) as part of standard follow-up. The clinical diagnosis of potential rejection was made using classical histopathology. One additional study sample was harvested and imaged by X-ray phase contrast imaging, producing 3D datasets with 0.65 µm pixel size, and up to 4,320 images per sample. An experienced pathologist graded both histopathological and X-ray phase contrast images in a blinded fashion. The agreement between methods was assessed by weighted kappa, showing substantial agreement (kappa up to 0.80, p < 0.01) between X-ray phase contrast imaging and classical histopathology. X-ray phase contrast imaging does not require tissue processing, allows thorough analysis of a full myocardial sample and allows identification of acute cellular rejection.

Quantitative ultrasound for non-invasive evaluation of subclinical rejection in renal transplantation.

OBJECTIVES: This study aimed to investigate the predictive efficacy of shear-wave elastography, superb microvascular imaging (SMI), and CEUS for allograft rejection in kidney transplants without graft dysfunction. METHODS: From January 2021 to November 2021, 72 consecutive patients who underwent both allograft biopsy and ultrasound were evaluated. Blood test results were obtained within a week of the ultrasound examinations, which were performed before the protocol biopsy. Resistive index (RI), tissue viscoelasticity, vascular index, and quantitative CEUS parameters were measured. Patients were divided based on biopsy results into the rejection and non-rejection groups. RESULTS: Among the 72 patients, 21 patients had pathological characteristics of acute rejection. RI of allograft was significantly higher in the rejection group (p = 0.007), compared to the non-rejection group. There were no significant between-group differences in vascular indices of SMI, mean elasticity, and mean viscosity. Meanwhile, among the parameters obtained by the time-intensity curve on CEUS, the cortical and medullary ratios of average contrast signal intensity, peak enhancement, wash-in area AUC, wash-in perfusion index, wash-out AUC, and wash-in and wash-out AUC were significantly different between the two groups (p < 0.05). In the receiver operating characteristic curve analysis for predicting allograft rejection, the AUC was 0.853 for the combination of six CEUS parameters, RI, and blood urea nitrogen. CONCLUSIONS: Among non-invasive quantitative ultrasound measurements, CEUS parameters are the most useful for diagnosing subclinical allograft rejection. Furthermore, the combination of CEUS parameters, RI, and blood urea nitrogen may be helpful for the early detection of renal allograft rejection. KEY POINTS: • Among non-invasive quantitative ultrasound measurements, CEUS parameters are the most useful for the diagnosis of subclinical allograft rejection. • On CEUS, the C/M ratios of MeanLin, PE, WiAUC, WiPI, WoAUC, and WiWoAUC are significantly lower in the rejection group; the combination of these showed reliable predictive performance for rejection. • The combination of CEUS parameters, RI, and BUN has a high predictive capability for subclinical allograft rejection.

Native T1 mapping detects both acute clinical rejection and graft dysfunction in pediatric heart transplant patients.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is emerging as an important tool for cardiac allograft assessment. Native T1 mapping may add value in identifying rejection and in assessing graft dysfunction and myocardial fibrosis burden. We hypothesized that CMR native T1 values and features of textural analysis of T1 maps would identify acute rejection, and in a secondary analysis, correlate with markers of graft dysfunction, and with fibrosis percentage from endomyocardial biopsy (EMB). METHODS: Fifty cases with simultaneous EMB, right heart catheterization, and 1.5 T CMR with breath-held T1 mapping via modified Look-Locker inversion recovery (MOLLI) in 8 short-axis slices and subsequent quantification of mean and peak native T1 values, were performed on 24 pediatric subjects. A single mid-ventricular slice was used for image texture analysis using nine gray-level co-occurrence matrix features. Digital quantification of Masson trichrome stained EMB samples established degree of fibrosis. Markers of graft dysfunction, including serum brain natriuretic peptide levels and hemodynamic measurements from echocardiography, catheterization, and CMR were collated. Subjects were divided into three groups based on degree of rejection: acute rejection requiring new therapy, mild rejection requiring increased ongoing therapy, and no rejection with no change in treatment. Statistical analysis included student's t-test and linear regression. RESULTS: Peak and mean T1 values were significantly associated with acute rejection, with a monotonic trend observed with increased grade of rejection. Texture analysis demonstrated greater spatial heterogeneity in T1 values, as demonstrated by energy, entropy, and variance, in cases requiring treatment. Interestingly, 2 subjects who required increased therapy despite low grade EMB results had abnormal peak T1 values. Peak T1 values also correlated with increased BNP, right-sided filling pressures, and capillary wedge pressures. There was no difference in histopathological fibrosis percentage among the 3 groups; histopathological fibrosis did not correlate with T1 values or markers of graft dysfunction. CONCLUSION: In pediatric heart transplant patients, native T1 values identify acute rejection requiring treatment and may identify graft dysfunction. CMR shows promise as an important tool for evaluation of cardiac grafts in children, with T1 imaging outperforming biopsy findings in the assessment of rejection.

Progression of Portal Hypertension in Acute Cellular Rejection After Liver Transplantation.

OBJECTIVES: This study was designed to investigate the frequency of computed tomography features indicating progression of portal hypertension and their clinical relevance in patients who experienced acute cellular rejection after liver transplantation. MATERIALS AND METHODS: This retrospective study included 141 patients with pathologically diagnosed acute cellular rejection following liver transplant. Patients were divided into early and late rejection groups according to the time of diagnosis. Two radiologists analyzed the interval changes in spleen size and variceal engorgement on computed tomography images obtained at the times of surgery and biopsy. Aggravation of splenomegaly and variceal engorgement were considered computed tomography features associated with the progression of portal hypertension. Clinical outcomes, including responses to treatment and graft survival, were compared between patients with and without these features. RESULTS: The frequency of progression of portal hypertension was 31.9% and did not differ significantly in patients who experienced early (30.8% [28/91]) and late (34.0% [17/50]) rejection (P = .694). In the late rejection group, computed tomography features indicating progression of portal hypertension were significantly associated with poor response to treatment (P = .033). Graft survival in both the early and late rejection groups did not differ significantly in patients with and without progression of portal hypertension. CONCLUSIONS: Computed tomography features suggesting the progression of portal hypertension were encountered in about one-third of patients who experienced acute cellular rejection after liver transplant. Progression of portal hypertension was significantly related to poor response to treatment in the late rejection group.

Hematological and biochemical characteristics and diagnostic imaging results in acute T cell-mediated rejection after pediatric liver transplantation.

BACKGROUND: Liver biopsy is the gold standard for diagnosing TCMR after LT. However, complications caused by liver biopsy may occur especially during the immediate post-transplantation period and other effective methods for predicting TCMR have not been established. Thus, we investigated whether hematological and biochemical characteristics and Doppler ultrasonography findings are associated with acute TCMR. METHODS: A multiple logistic regression analysis was performed to identify the prognostic factors of acute TCMR, defined as a RAI ≥4. Then, a ROC curve analysis was conducted to evaluate for diagnostic performance. The relationship between prognostic factors and each histological category of RAI was investigated. RESULTS: Eighty-nine liver biopsies were performed on 85 patients between January 2012 and December 2019. The RAI of 62 (69.7%) liver biopsies was ≥4. AEC (×104 /µl), direct bilirubin level (mg/dl), and MHVV (cm/s) were found to be associated with acute TCMR (OR: 4.96, 95% CI: 1.44-17.0, p = .011; OR: 1.41, 95% CI: 1.04-1.91, p = .025; OR: 1.05, 95% CI: 1.02-1.08, p < .001, respectively). The area under the ROC curves for predicting acute TCMR was 0.86 (95% CI: 0.78-0.94). There was a correlation between AEC, direct bilirubin level, and MHVV as well as the severity of RAI. CONCLUSIONS: AEC, direct bilirubin level, and MHVV were the independent risk factors for acute TCMR. This study could provide information regarding the identification of patients requiring liver biopsy.

Changes in circumferential strain can differentiate pediatric heart transplant recipients with and without graft rejection.

BACKGROUND: Routine surveillance protocols rely heavily on endomyocardial biopsy (EMB) for detection of rejection in pediatric heart transplant recipients. More sensitive echocardiographic tools to assess rejection may help limit the number of EMBs. This study compared changes in left ventricular (LV) strain in patients who had rejection versus those who did not. METHODS: A single center retrospective review was conducted between 2013 and 2020. Patients were categorized based on rejection history. Echocardiograms were evaluated at the time of 2 consecutive EMBs; in the rejection group, the second echocardiogram was collected at the time of a rejection episode. Conventional measures of LV function and speckle-tracking echocardiography-derived longitudinal (LS) and circumferential strain (CS) were measured. RESULTS: 17 patients were in the non-rejection group and 17 were in the rejection group (30 total rejection episodes). The rejection group was older at the time of transplant (12.5 vs. 1.3 years, p = .01). A decline in CS was seen in the rejection group at the second echocardiogram [-18.5 (IQR -21.5, -14.6) to -15.7 (IQR -19.8, -13.2)] while CS improved in the non-rejection group [-20.8 (IQR -23.9, -17.8) to -23.9 (IQR -24.9, -20.1)]. This difference in change reached significance (p = .02). A similar pattern was seen in LS that neared significance (p = .06). There was no significant difference in ejection fraction change (p = .24). CONCLUSIONS: Patients in the non-rejection group displayed improvement in CS between echocardiograms while patients in the rejection group showed subsequent decline. Worsening of LV CS may help identify acute rejection in the early post-transplant period.

Long-term experience using CNI-free immunosuppression in selected paediatric heart transplant recipients.

BACKGROUND: CNI-free immunosuppression with conversion to mTORi-based immunosuppression has been demonstrated to reduce CNI-toxicity and to exhibit anti-proliferative properties. However, the experience of CNI-free immunosuppression in paediatric heart transplantation is limited. METHODS: A retrospective analysis was conducted of 129 paediatric heart transplants performed between 1997 and 2015. Fifteen patients with clinically indicated conversion from CNI-based to CNI-free immunosuppression were identified. Survival data, rejection episodes, renal function, post-transplantation lymphoproliferative disorder and CAV, including examination with OCT were analysed. RESULTS: Immunosuppression conversion was successful in all patients. Fourteen of 15 patients (93%) are currently living with good graft function. Median post-transplant survival was 15 years (range, 5-23 years), and median follow-up since conversion was 6 years (range, 1-11 years). Mild (grade 1R) ACR was present in three patients after discontinuation of CNIs. The recovery of renal function with a significant increase in eGFR was observed at 1 and 3 years after conversion. No patient had angiographic signs of macroscopic CAV according to the current ISHLT classification; however, OCT showed the signs of angiographically silent CAV in all patients. CAV did not progress in any patient, implying CAV was stabilised by mTORi-based CNI-free immunosuppression. CONCLUSIONS: CNI-free immunosuppression based on mTORis is a safe and appropriate strategy for maintenance therapy in selected paediatric patients, significantly improves renal function and stabilises CAV. OCT revealed early development of angiographically silent CAV.

[18F]FDG PET/CT imaging disproves renal allograft acute rejection in kidney transplant recipients with acute kidney dysfunction: a validation cohort.

PURPOSE: [18F]FDG PET/CT may predict the absence of acute allograft rejection (AR) in kidney transplant recipients (KTRs) with acute kidney injury (AKI). Still, the proposed threshold of 1.6 of the mean of mean standardized uptake values (mSUVmean) in the renal parenchyma needs validation. METHODS: We prospectively performed 86 [18F]FDG PET/CT in 79 adult KTRs who underwent per-cause transplant biopsy for suspected AR. Biopsy-proven polyoma BK nephropathies (n = 7) were excluded. PET/CT was performed 192 ± 18 min after administration of 254.4 ± 30.4 MBq of [18F]FDG. The SUVmean was measured in both upper and lower poles of the renal allograft. One-way analysis of variance (ANOVA) and Tukey's studentized range test were sequentially performed. The receiver operating characteristic (ROC) curve was drawn to discriminate "AR" from non-pathological ("normal" + "borderline") conditions. RESULTS: The median age of the cohort was 55 [43; 63] years, with M/F gender ratio of 47/39. The mean eGFR was 31.9 ± 14.6 ml/min/1.73m2. Biopsies were categorized in 4 groups: "normal" (n = 54), "borderline" (n = 9), "AR" (n = 14), or "others" (n = 2). The median [min; max] mSUVmean reached 1.72 [1.02; 2.07], 1.97 [1.55; 2.11], 2.13 [1.65, 3.12], and 1.84 [1.57; 2.12] in "normal," "borderline," "AR," and "others" groups, respectively. ANOVA demonstrated a significant difference of mSUVmean among groups (F = 13.25, p < 0.0001). The ROC area under the curve was 0.86. Test sensitivity and specificity corresponding to the threshold value of 1.6 were 100% and 30%, respectively. CONCLUSION: [18F]FDG PET/CT may help noninvasively prevent inessential transplant biopsies in KTR with AKI.

Noninvasive Radionuclide Molecular Imaging of the CD4-Positive T Lymphocytes in Acute Cardiac Rejection.

Heart transplantation (HT) is an effective treatment for end-stage heart disease. However, acute rejection (AR) is still the main cause of death within one year after HT. AR is an acute immune response mediated by T lymphocytes, mainly CD4+ T lymphocytes. This study innovatively develops a radiolabeled probe 99mTc-HYNIC-mAbCD4 for noninvasive visualization of CD4+ T lymphocyte infiltration and detection of AR. The 99mTc-HYNIC-mAbCD4 and its isotype control 99mTc-HYNIC-IgG were successfully prepared and characterized. The specificity and affinity of the probe in vitro were assessed by cell-binding experiments. Binding of 99mTc-HYNIC-mAbCD4 to CD4+ T lymphocytes was higher than that of the macrophages and IgG probe groups, and mAbCD4 was effective in the blockade of the binding reaction. The biodistribution data confirmed the SPECT/CT images, with significantly higher levels of 99mTc-HYNIC-mAbCD4 observed in allografts compared to allograft treatment (10 mg/kg/d Cyclosporin A subcutaneously for 5 consecutive days after surgery), isografts, or in rats which received allografts injected with 99mTc-HYNIC-IgG. Histological examination confirmed more CD4+ T lymphocyte infiltration in the allograft hearts than other groups. In summary, 99mTc-HYNIC-mAbCD4 achieved high affinity and specificity of binding to CD4+ T lymphocytes and accumulation in the transplanted heart. Radionuclide molecular imaging with 99mTc-HYNIC-mAbCD4 may be a potential diagnostic method for acute cardiac rejection.

Protocol liver biopsies in stable long-term pediatric liver transplant recipients: risk or benefit?

BACKGROUND: Follow-up after pediatric liver transplantation (LTX) is challenging and needs to be refined to extend graft survival as well as general functional health and patients´ quality of life. Strategies towards individual immunosuppressive therapy seem to play a key role. Our aim was to evaluate protocol liver biopsies (PLB) as a tool in personalized follow up after pediatric LTX. PATIENTS AND METHODS: Our retrospective analysis evaluates 92 PLB in clinically asymptomatic pediatric patients after LTX between 2009 and 2019. Histological findings were characterized using the Desmet scoring system. In addition to PLB, other follow-up tools like laboratory parameters, ultrasound imaging and transient elastography were evaluated. Risk factors for development of fibrosis or inflammation were analyzed. RESULTS: PLB revealed a high prevalence of graft fibrosis (67.4%) and graft inflammation (47.8%). Graft inflammation was significantly (P = 0.0353*) more frequent within the first 5 years after transplantation compared to later time points. Besides conventional ultrasound, the measurement of liver stiffness using transient elastography correlate with stage of fibrosis (r = 0.567, P = <0.0001***). Presence of donor-specific anti-human leukocyte antigen antibodies in blood correlates with grade of inflammation in PLB (r = 0.6040, P = 0.0018 **). None of the patients who underwent PLB suffered from intervention-related complications. Histopathological results had an impact on clinical decision making in one-third of all patients after PLB. CONCLUSION: PLB are a safe and useful tool to detect silent immune-mediated allograft injuries in the context of normal liver parameters.

The Cologne rebubbling study: a reappraisal of 624 rebubblings after Descemet membrane endothelial keratoplasty.

BACKGROUND/AIMS: To analyse graft detachments prior to rebubbling, the influence of rebubbling on the postoperative outcome after Descemet membrane endothelial keratoplasty (DMEK) and the need for rebubbling on the contralateral eye. METHODS: In this retrospective cohort study, out of 1541 DMEKs, optical coherence tomography scans and clinical records of 499 eyes undergoing rebubbling after DMEK at the University Hospital of Cologne, Cologne, Germany, were examined. Main Outcome measures were (a) number, localisation and size of graft detachments; (b) influence of rebubbling/s on postoperative outcome after 12 months; and (c) rebubbling risk of the contralateral eye after DMEK. RESULTS: Mean number of detachment areas was 2.02±0.9. Mean lateral diameter of all detachments was 4534.76±1920.83 µm. Mean axial diameter was 382.53±282.02 µm. Detachments were equally distributed over all regions of the cornea. Best spectacle corrected visual acuity ( BSCVA) after 12 months was 0.197±0.23 logarithm of the minimum angle of resolution, endothelial cell density (ECD) was 1575.21±397.71 cells/mm2 and mean central corneal thickness (CCT) was 566.37±68.11 µm. BSCVA, CCT, ECD or endothelial cell loss of all rebubbled patients were not influenced by the number of rebubblings or the time between DMEK and rebubbling. Of the rebubbled patients, which received a DMEK subsequently on the other eye, 193 (58.8%) also received a rebubbling, which was significantly higher, when compared to the overall rebubbling rate of 32.3% (p=0.000). CONCLUSIONS: The overall number of rebubblings has no influence on the postoperative outcome after DMEK, if a rebubbling becomes necessary. Patients who received a rebubbling on one eye have an elevated risk for a rebubbling on the fellow eye.

Clinical Significance of Renal Allograft Urothelial Thickening Identified by Ultrasound.

OBJECTIVES: To assess the etiology and clinical implications of ultrasound (US)-diagnosed urothelial thickening (UT) in renal transplants. METHODS: Patients with renal transplants who had UT diagnosed by US from January 2000 to December 2018 were retrospectively identified and compared to patients with transplants without UT scanned during the study period. Medical records were reviewed for demographics, US findings, pathologic results, laboratory values, and clinical outcomes and compared between groups by Fisher exact and t tests. RESULTS: A total of 143 patients with UT and 128 controls comprised our cohorts. The patient age in the UT group versus controls (mean ± SD, 50.2 ± 16.5 versus 51.2 ± 15.3 years) and the time since transplant (2.9 ± 4.2 versus 2.4 ± 5.8 years) were similar. Patients with UT were more likely to be female than controls (76 of 143 [53.1%] versus 53 of 128 [41.4%]; P = .07), but the difference was not statistically significant, and patients with UT were more likely to have indwelling stents (31 of 143 [21.7%] versus 9 of 128 [7.0%]; P = .001) and hydronephrosis (25 of 143 [17.4%] versus 11 of 128 [8.6%]; P = .03). At biopsy, rejection and vascular sclerosis were more likely in patients with UT compared to controls (24 of 25 [49.0%] versus 11 of 43 [25.6%]; P = .031; 42 of 49 [85.7%] versus 22 of 43 [51.2%]; P = .0005, respectively), whereas acute tubular necrosis was similar. The sensitivity (50.0%) and specificity (74.4%) of UT for rejection were low. CONCLUSIONS: Urothelial thickening correlates with US findings of urinary obstruction and indwelling stents, suggesting a possible mechanical component to UT's etiology. Although transplant rejection and vascular sclerosis were more frequent at biopsy in the UT group than controls, UT had low sensitivity and specificity for rejection.

Impact of Re-bubbling after Descemet Membrane Endothelial Keratoplasty on Long-term Results.

Purpose/Aim of the study: Graft detachment after DMEK can be treated easily with an additional air injection - re-bubbling. The aim of our study was to investigate the effect of a re-bubbling on the postoperative outcome.Materials and Methods: In this retrospective, comparative, cohort study we included eyes from patients that underwent DMEK surgery. A graft detachment was diagnosed by slit-lamp examination and OCT scan. All eyes were divided into three groups: no re-bubbling, one re-bubbling, more than one re-bubbling. We analyzed the visual acuity, endothelial cell density and rate of graft failure.Results: In 163 of 463 eyes (35.2%) a re-bubbling was performed (119 eyes 1 re-bubbling, 44 eyes more than one re-bubbling). Visual acuity improved significantly in all groups. After controlling for donor age, reason for surgery, time of cultivation of the graft and preoperative visual acuity, no difference in the visual acuity was seen at any point of follow-up. All patients showed a significant reduction in endothelial cell density 1 month after DMEK. Controlling for donor age, reason for surgery, type of surgery (DMEK-only or DMEK combined with cataract surgery) and the time of cultivation of the graft, the difference in endothelial cell density at 1 month post-surgery between no re-bubbling and one re-bubbling was 157 cells/mm2 (95% CI 2-310, p = .047) and between no re-bubbling and more than one re-bubbling 504 cells/mm2 (95% CI 267 - 741, p < .001). The difference in endothelial cell density remained over the course of follow-up. Twenty patients (4.3%) developed a graft failure during postoperative follow-up. Controlling for donor age, reason for surgery and the time of cultivation of the graft, we did not find any difference in the risk of graft failure between re-bubbling categories.Conclusions: Re-bubbling increased the risk for an endothelial cell loss, but did not influence the postoperative visual acuity and the rate of graft failure.

Diagnosis of Acute Rejection of Liver Grafts in Young Children Using Acoustic Radiation Force Impulse Imaging.

OBJECTIVE. Frequency of acute rejection (AR) after pediatric liver transplant remains high despite progress in immunosuppression. Liver biopsy (LB) is the reference standard for the diagnosis of AR despite its potential for morbidity. The purpose of our study was to evaluate the ability of acoustic radiation force impulse (ARFI) imaging to distinguish AR from other causes of short- and medium-term liver dysfunction and to identify liver transplant cases with normal liver function. MATERIALS AND METHODS. ARFI imaging was used to evaluate shear wave velocity (SWV) after liver transplant in young children. All pediatric liver grafts that had LB and ARFI examination between January 2014 and December 2017 were included in this retrospective study. Results of LB were compared with those of SWV. Collected data included age at biopsy and transplant, sex, weight, height, body mass index, interval between liver transplant and shear wave elastography and LB, kind of graft, type of donor, and diagnosis at transplant. ROC curve analysis was performed to assess the diagnostic performance of SWV. Optimal cutoff of SWV using ARFI imaging in predicting AR was identified using the Youden index. RESULTS. Statistical analysis was performed on 54 children; six of the original 60 were excluded because of confounding alterations or changes in outcome. Median SWV was higher in patients with AR (2.03 m/s; interquartile range [IQR], 1.80-2.45 m/s) compared with those with idiopathic hepatitis (1.33 m/s; IQR, 1.12-1.53 m/s), portal hypertension (1.42 m/s; IQR, 1.32-1.72 m/s), cholangitis (1.56 m/s; IQR, 1.07-1.62 m/s) or normal liver function (1.23 m/s; IQR 1.12-1.29 m/s) at protocol biopsies (all comparisons, p < 0.01). SWV higher than 1.73 m/s was predictive for AR (AUC, 0.966). SWV also showed good diagnostic accuracy in normal liver function (AUC, 0.791). ARFI imaging was not predictive for hepatitis (AUC, 0.402), portal hypertension (AUC, 0.556), or cholangitis (AUC, 0.420). CONCLUSION. ARFI imaging could be routinely used in place of LB in pediatric patients with liver dysfunction after liver transplant, restricting indication and risks of biopsy to selected cases.

Acoustic Radiation Force Impulse Elastography May Predict Acute Rejection in Kidney Transplantation.

BACKGROUND: Allograft biopsy that is done as indicated by clinical and laboratory clues about graft rejection provides a definitive diagnosis. Noninvasive methods that may be useful for predicting or diagnosing rejection are important for early diagnosis of possible rejection. PURPOSE: The aim of this study is to investigate the relationship between changes in shear wave velocity (SWV) values and renal allograft kidney biopsy findings. MATERIAL AND METHODS: Thirty-four end-stage renal failure patients who underwent living donor renal transplantation between January 2015 and July 2015 were enrolled in this prospective cohort study. Implantation, sixth-month protocol, and biopsies that were performed with suspicion of acute rejection were evaluated with renal Doppler ultrasound and elastography findings of recipients' preimplantation donor ultrasonography findings. RESULTS: Comparison of renal ultrasound and elastography findings of 2 groups revealed a significant elevation in the resistive index (0.81 vs 0.63, P = .005) and pulsatility index (2.08 vs 1.20, P = .008) values in the rejection group, and no significant difference in the SWV values between the 2 groups. Delta (Δ)-SWV was calculated using the difference between acute rejection values and preimplantation, implantation, and sixth-month values showed a positive correlation between acute rejection (Δ-sixth month, r = 0.498, P = .030), tubulitis (Δ-pretransplant, r = 0.509, P = .037), and inflammation (Δ-pretransplant, r = 0.657, P = .004) scores. However, there were no correlations between Δ-SWV values and glomerulitis and peritubular capillaritis score. CONCLUSION: Changes in SWV may predict acute rejection in kidney transplantation patients if the reference measurements were done at a more stable time after the transplantation.

Comparison of tissue Doppler imaging and conventional echocardiography to discriminate rejection from non-rejection after pediatric heart transplantation.

TDI is considered superior to conventional echocardiography for detecting changes in graft function during rejection in adults but has not demonstrated after pediatric OHT. We retrospectively analyzed echocardiograms performed within 24 hours of biopsy in 122 recipients with median age of 8.7 years. Using biopsy findings as the gold standard, we compared paired rejection and non-rejection echocardiograms using each patient as their own control. We included pairs of LV dimensions, FS, volumes, mass, mass/volume, sphericity, wall stress, SSI, SVI, and TDI velocities in this comparison. C-statistic was used to assess discrimination for individual echo variables and combinations of variables. Overall, 647 non-rejection and 24 rejection biopsy-echo pairs were identified. There was a significant decline in TDI velocities and their Z-scores during rejection but not in conventional variables (P ≤ .005). The variable that best discriminated rejection from non-rejection was LV S', with C-statistic = 0.93. Conventional echo variables performed less well with C-statistic range 0.65-0.67 for LV EF, shortening fraction, and mass. TDI is superior to conventional echocardiography measures for discriminating rejection from non-rejection. The use of newer non-invasive parameters to detect myocardial dysfunction and shifting the paradigm of rejection surveillance to detection of non-rejection together provide a promising approach to reducing the need for biopsy in pediatric heart recipients.