Mortality and severe neurological morbidity in extremely preterm growth-restricted fetuses.

OBJECTIVE: To develop a model for the prediction of adverse perinatal outcome in growth-restricted fetuses requiring delivery before 28 weeks in order to provide individualized patient counseling. METHODS: This was a retrospective multicenter cohort study of singleton pregnancies with antenatal suspicion of fetal growth restriction requiring delivery before 28 weeks' gestation between January 2010 and January 2020 in six tertiary public hospitals in the Barcelona area, Spain. Separate predictive models for mortality only and mortality or severe neurological morbidity were created using logistic regression from variables available antenatally. For each model, predictive performance was evaluated using receiver-operating-characteristics (ROC)-curve analysis. Predictive models were validated externally in an additional cohort of growth-restricted fetuses from another public tertiary hospital with the same inclusion and exclusion criteria. RESULTS: A total of 110 cases were included. The neonatal mortality rate was 37.3% and, among the survivors, the rate of severe neurological morbidity was 21.7%. The following factors were retained in the multivariate analysis as significant predictors of mortality: magnesium sulfate neuroprotection, gestational age at birth, estimated fetal weight, male sex and Doppler stage. This model had a significantly higher area under the ROC curve (AUC) compared with a model including only gestational age at birth (0.810 (95% CI, 0.730-0.889) vs 0.695 (95% CI, 0.594-0.795); P = 0.016). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 66%, 80% and 66%, respectively. For the prediction of the composite adverse outcome (mortality or severe neurological morbidity), the model included: gestational age at birth, male sex and Doppler stage. This model had a significantly higher AUC compared with a model including only gestational age at birth (0.810 (95% CI, 0.731-0.892) vs 0.689 (95% CI, 0.588-0.799); P = 0.017). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 55%, 63% and 74%, respectively. External validation of both models yielded similar AUCs that did not differ significantly from those obtained in the original sample. CONCLUSIONS: Estimated fetal weight, fetal sex and Doppler stage can be combined with gestational age to improve the prediction of death or severe neurological sequelae in growth-restricted fetuses requiring delivery before 28 weeks. This approach may be useful for parental counseling and decision-making. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic accuracy of first-trimester combined screening for early-onset and preterm pre-eclampsia at 8-10 compared with 11-13 weeks' gestation.

OBJECTIVES: To compare the ability of first-trimester combined screening for pre-eclampsia (PE) to predict early-onset and preterm PE when pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) were assessed before vs after 11 weeks' gestation. METHODS: This was a secondary analysis of a prospective cohort study of singleton pregnancies undergoing routine first-trimester screening conducted at Vall d'Hebron University Hospital, Barcelona, Spain, between October 2015 and September 2017. Demographic characteristics, obstetric history, maternal history and biophysical markers (mean uterine artery pulsatility index and mean arterial blood pressure (MAP)) were recorded at the first-trimester scan (at 11 + 0 to 13 + 6 weeks' gestation). Maternal serum concentrations of PAPP-A and PlGF were assessed from the routine first-trimester blood test (at 8 + 0 to 13 + 6 weeks). Women were classified into two groups depending on whether serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks or at 11 + 0 to 13 + 6 weeks. Probability scores for early-onset and preterm PE were calculated by using two different algorithms: the multivariate Gaussian-distribution model and The Fetal Medicine Foundation (FMF) competing-risks model. Receiver-operating-characteristics (ROC) curves were produced and detection rates at fixed 5% and 10% false-positive rates were computed to compare the performance of these algorithms when PAPP-A and PlGF were assessed before vs after 11 weeks. RESULTS: Of the 2641 women included, serum biomarkers were assessed before 11 weeks in 1675 (63.4%) and at or after 11 weeks in 966 (36.6%). Of these, 90 (3.4%) women developed PE, including 11 (0.4%) cases of early-onset PE and 30 (1.1%) of preterm PE. Five (45.5%) cases of early-onset and 16 (53.3%) of preterm PE were identified in the group in which serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks and six (54.5%) cases of early-onset and 14 (46.7%) of preterm PE in the group in which serum biomarkers were assessed at 11 + 0 to 13 + 6 weeks. In the prediction of early-onset and preterm PE using the Gaussian algorithm, no differences were observed between the areas under the ROC curves (AUCs) when PAPP-A and PlGF were measured before or after 11 weeks. In the prediction of early-onset and preterm PE using the FMF algorithm, no differences were observed between AUCs for any of the combinations used for risk calculation when the serum biomarkers were obtained before vs after 11 weeks, except for the combination of PAPP-A and MAP, which showed a greater AUC for the prediction of early-onset PE when PAPP-A was measured at or after 11 weeks. CONCLUSIONS: The prediction of early-onset and preterm PE is similar when serum biomarkers are measured before or after 11 weeks. This allows the use of a two-step approach for PE risk assessment that permits immediate risk calculation at the time of the first-trimester scan. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Unusual aortic valve anomaly in the fetus: a case report.

Aortic valve anomalies in fetal life usually concern aortic valve stenosis, in severe forms associated to left ventricular impairment - endocardial fibroelastosis and mitral valve insufficiency. Isolated aortic regurgitation in utero is infrequent and is usually considered to be due to a rare anomaly: aorto-left ventricular tunnel. We describe an unusual case of fetal aortic valve anomaly with severe dysplasia, with a marked regurgitant flow through the aortic valve, passing in a retrograde way from the duct, associated with a marked left ventricular endocardial fibroelastosis and dysfunction, resulting in the fatal outcome of the case.

Characterization and differentiation of equine tendon-derived progenitor cells.

Mesenchymal stem cells have been recently investigated for their potential use in regenerative medicine. Population of adult stem cells were recently identified in human and lab animal tendons, but no detailed investigations have been made in the equine species. The aim of our study is to identify a progenitor cell population from tendon tissue (TSPCs) in the horse superficial digital flexor tendon that are able to be highly clonogenic, to grow fast and to differentiate in different induced cell lineages as well as bone marrow derived progenitor cells (BM-MSCs). The hypothesis that TSPCs possess a mesenchymal stem cell behavior opens a new prospective for tendon regenerative medicine approaches. TSPCs were expanded more rapidly and showed higher plating efficiency when compared with BM-MSCs. Both cell lines expressed identical stem cell markers in vitro and they were able to differentiate towards osteogenic and adipogenic lineages as demonstrated with cytochemical staining and mRNA gene expression. TSPCs showed a positive but limited chondrogenic differentiation compared with BM-MSCs as demonstrated by histological and biochemical analyses. According to our results, equine TSPCs have high clonogenic properties and proliferating potential, they express stem cell markers and have the capability to be multipotent as well as BM-MSCs. These findings suggest that TSPCs may represent a good model for stem cell biology and could be useful for future tendon regenerative medicine investigations.

Are ankle chondrocytes from damaged fragments a suitable cell source for cartilage repair?

OBJECTIVE: To characterize the post-expansion cartilage-forming capacity of chondrocytes harvested from detached fragments of osteochondral lesions (OCLs) of ankle joints (Damaged Ankle Cartilage Fragments, DACF), with normal ankle cartilage (NAC) as control. DESIGN: DACF were obtained from six patients (mean age: 35 years) with symptomatic OCLs of the talus, while NAC were from 10 autopsies (mean age: 55 years). Isolated chondrocytes were expanded for two passages and then cultured in pellets for 14 days or onto HYAFF-11 meshes (FAB, Italy) for up to 28 days. Resulting tissues were assessed histologically, biochemically [glycosaminoglycan (GAG), DNA and type II collagen (CII)] and biomechanically. RESULTS: As compared to NAC, DACF contained significantly lower amounts of DNA (3.0-fold), GAG (5.3-fold) and CII (1.5-fold) and higher amounts of type I collagen (6.2-fold). Following 14 days of culture in pellets, DACF-chondrocytes generated tissues less intensely stained for Safranin-O and CII, with significantly lower GAG contents (2.8-fold). After 28 days of culture onto HYAFF((R))-11, tissues generated by DACF-chondrocytes were less intensely stained for Safranin-O and CII, contained significantly lower amounts of GAG (1.9-fold) and CII (1.4-fold) and had lower equilibrium (1.7-fold) and dynamic pulsatile modulus (3.3-fold) than NAC-chondrocytes. CONCLUSION: We demonstrated that DACF-chondrocytes have inferior cartilage-forming capacity as compared to NAC-chondrocytes, possibly resulting from environmental changes associated with trauma/disease. The study opens some reservations on the use of DACF-derived cells for the repair of ankle cartilage defects, especially in the context of tissue engineering-based approaches.

A novel implantation technique for engineered osteo-chondral grafts.

We present a novel method to support precise insertion of engineered osteochondral grafts by pulling from the bone layer, thereby minimizing iatrogenic damage associated with direct manipulation of the cartilage layer. Grafts were generated by culturing human expanded chondrocytes on Hyaff-11 meshes, sutured to Tutobone spongiosa cylinders. Through the bone layer, shaped to imitate the surface-contours of the talar dome, two sutures were applied: the first for anterograde implantation, to pull the graft into the defect, and the second for retrograde correction, in case of a too deep insertion. All grafts could be correctly positioned into osteochondral lesions created in cadaveric ankle joints with good fit to the surrounding cartilage. Implants withstood short-term dynamic stability tests applied to the ankle joint, without delamination or macroscopic damage. The developed technique, by allowing precise and stable positioning of osteochondral grafts without iatrogenic cartilage damage, is essential for the implantation of engineered tissues, where the cartilage layer is not fully mechanically developed, and could be considered also for conventional autologous osteochondral transplantation.

Intra-individual comparison of human ankle and knee chondrocytes in vitro: relevance for talar cartilage repair.

OBJECTIVE: As compared to knee chondrocytes (KC), talar chondrocytes (TC) have superior synthetic activity and increased resistance to catabolic stimuli. We investigated whether these properties are maintained after TC are isolated and expanded in vitro. METHODS: Human TC and KC from 10 cadavers were expanded in monolayer and then cultured in pellets for 3 and 14 days or in hyaluronan meshes (Hyaff-11) for 14 and 28 days. Resulting tissues were assessed biochemically, histologically, biomechanically and by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The proteoglycan and collagen synthesis rates in the pellets were also measured following exposure to Interleukin-1 beta (IL-1 beta). RESULTS: After 14 days of pellet culture, TC and KC expressed similar levels of type I collagen (CI) and type II collagen (CII) mRNA and the resulting tissues contained comparable amounts of glycosaminoglycans (GAG) and displayed similar staining intensities for CII. Also proteoglycan and collagen synthesis were similar in TC and KC pellets, and dropped to a comparable extent in response to IL-1 beta. Following 14 days of culture in Hyaff-11, TC and KC generated tissues with similar amounts of GAG and CI and CII. After 28 days, KC deposited significantly larger fractions of GAG and CII than TC, although the trend was not reflected in the measured biomechanical properties. CONCLUSION: After isolation from their original matrices and culture expansion, TC and KC displayed similar biosynthetic activities, even in the presence of catabolic stimuli. These in vitro data suggest a possible equivalence of TC and KC as autologous cell sources for the repair of talar cartilage lesions.

Engineered cartilage generated by nasal chondrocytes is responsive to physical forces resembling joint loading.

OBJECTIVE: To determine whether engineered cartilage generated by nasal chondrocytes (ECN) is responsive to different regimens of loading associated with joint kinematics and previously shown to be stimulatory of engineered cartilage generated by articular chondrocytes (ECA). METHODS: Human nasal and articular chondrocytes, harvested from 5 individuals, were expanded and cultured for 2 weeks into porous polymeric scaffolds. The resulting ECN and ECA were then maintained under static conditions or exposed to the following loading regimens: regimen 1, single application of cyclic deformation for 30 minutes; regimen 2, intermittent application of cyclic deformation for a total of 10 days, followed by static culture for 2 weeks; regimen 3, application of surface motion for a total of 10 days. RESULTS: Prior to loading, ECN constructs contained significantly higher amounts of glycosaminoglycan (GAG) and type II collagen compared with ECA constructs. ECN responded to regimen 1 by increasing collagen and proteoglycan synthesis, to regimen 2 by increasing the accumulation of GAG and type II collagen as well as the dynamic modulus, and to regimen 3 by increasing the expression of superficial zone protein, at the messenger RNA level and the protein level, as well as the release of hyaluronan. ECA constructs were overall less responsive to all loading regimens, likely due to the lower extracellular matrix content. CONCLUSION: Human ECN is responsive to physical forces resembling joint loading and can up-regulate molecules typically involved in joint lubrication. These findings should prompt future in vivo studies exploring the possibility of using nasal chondrocytes as a cell source for articular cartilage repair.

A case of fibrous histiocytoma of the trachea in an infant treated by endobronchial ND:YAG laser.

Fibrous histiocytomas are uncommon tracheal tumors. They generally involve only the lung parenchyma; endobronchial involvement is extremely rare. At present, surgical resection is considered the therapy of choice for definitive diagnosis and cure. Endoscopical treatment is uncommon in pediatric patients because of the technical endoscopical difficulties and the high recurrence rate of treatment by endoscopy alone. We report the first case of fibrous histiocytoma in an infant successfully treated by endoscopy and yttrium alluminum garnet (YAG)-laser.

Massive haemoptysis after living donor liver transplantation.

A 27 year old man with hereditary haemorrhagic telangiectasia who developed progressive liver dysfunction underwent living related right lobe transplantation. Pulmonary arteriography did not reveal arteriovenous malformation or abnormal intrapulmonary venous channels. The postoperative course was characterised by persistent hypoxaemia and respiratory failure developed. On day 6, a massive haemoptysis developed and the patient died shortly thereafter. The native liver showed a nodular pseudocirrhotic transformation, with highly dilated and irregularly interconnected vein-like or arterial-like structures in the fibrous septa. Pathological examination of both lungs showed irregular thickening of the wall of the arteries, secondary to eccentric and/or concentric myointimal hyperplasia. This case suggests that massive haemoptysis can develop even when arteriovenous malformations are undetectable by pulmonary arteriography, and it questions the role and the appropriateness of living donor liver transplantation in high risk patients.

Kaposi's sarcoma in liver transplant recipients: morphological and clinical description.

The clinical course and outcome of 5 adult patients who underwent orthotopic liver transplantation (OLT) and developed Kaposi's sarcoma (KS) is reported. From October 1986 to July 2000, a total of 459 patients underwent 499 OLTs at our hospital. The immunosuppressive regimen consisted of cyclosporine, azathioprine, prednisone, and antithymocyte globulin. Tacrolimus was administered only in selected patients. Five patients developed KS, and the pathological diagnosis was established months 9 to 23 after OLT. Four of 5 patients died of KS, surviving 0 to 6 months after pathological diagnosis. The fifth patient, with KS confined to the skin, is disease free 6 months after diagnosis. All patients were treated with reduction of immunosuppressive therapy and/or chemotherapy. Retrospective molecular investigation by polymerase chain reaction for human herpesvirus type 8 DNA detected specific viral sequences in histological specimens of tissues involved by KS. In our experience with adult liver transplant recipients, we registered a slightly lower prevalence of KS compared with other reported data, but observed a high rate of graft involvement and mortality.

Low nitric oxide values associated with low levels of zinc and high levels of cardiac necrosis markers detected in the plasma of rabbits treated with L-NAME.

Nitric oxide plays a key role as a vasodilating agent and its deficiency is associated with ischemic heart diseases. The aim of this study was to induce biochemical alterations associated with ischemic heart lesions by blocking nitric oxide synthase. L-NAME, a nitric oxide synthase inhibitor, was administered to rabbits and its effects on blood pressure, plasma levels of nitric oxide, zinc and cardiac necrosis markers, heart histology, and electrocardiographic profile were examined. L-NAME administration reduced the nitric oxide levels and consequently increased the diastolic blood pressure. It also caused small areas of myocardial coagulative necrosis, whose dispersed nature made it undetectable by electrocardiograph, and decreased the plasma levels of zinc, which is involved in the enzymatic activities that remove the peroxides damaging the myocardium. This model is proposed for the development of drugs affecting nitric oxide levels with the aim of controlling coronary ischemia.

Adjunctive thrombus aspiration and mechanical protection from distal embolization in primary percutaneous intervention for acute myocardial infarction.

Primary percutaneous intervention for acute occlusion of a native coronary artery may be complicated by distal embolization of plaque or thrombotic debris, with infarct extension. We tested the clinical application of a new therapeutic strategy combining maximal antiplatelet therapy, with glycoprotein IIb/IIIa inhibition, and adjunctive mechanical protection from distal embolization and direct aspiration of thrombus with a new balloon and catheter system (PercuSurgetrade mark). Successful aspiration of thrombus could be obtained in 7 out of 8 attempted procedures, with inability to negotiate the angulated take-off of the circumflex coronary artery in one patient. The current mechanical characteristics of the device, primarily developed for use in larger saphenous vein grafts, and certain caveats and limitations are discussed. New dedicated systems should be available in the near future for the native coronary circulation. Excellent immediate angiographic results were obtained in all treated patients, without evidence of loss of distal branches and no intraprocedural complications.

Validation of a high performance liquid chromatographic method for alpha amanitin determination in urine.

The objective of the present study was to develop and validate a liquid chromatographic method with electrochemical detection to measure alpha amanitin concentrations in urine after sample pretreatment with double mechanism (reversed phase/cation exchange) solid-phase extraction cartridges. The urine samples (10 ml) were purified and concentrated to 1 ml with elimination of matrix contaminants. The extracts were then separated by isocratic reversed-phase chromatography using a C18 column (4.6 mm x 25 cm) with a mobile phase composed of 0.005 M phosphate buffer (pH 7.2) and acetonitrile (90:10). Coulometric detection was performed by applying an oxidation potential of +500 mV to a porous graphite electrode in a low-volume analytical cell. The limit of quantitation was 10 ng/ml with a signal-to-noise ratio = 25. The linearity studied on spiked urine was satisfactory (r = 0.9966) from 10 ng/ml to 200 ng/ml. The average extraction recovery of alpha amanitin was 78%, determined using spiked urine samples ranging from 10-300 ng/ml. The intra-assay precision was checked at 10, 50 and 100 ng/ml levels (n = 10) in spiked urine samples, with resulting coefficients of variation of 3.6%, 2% and 1.5%, respectively.

A semiquantitative approach to the evaluation of acute cardiac allograft rejection at endomyocardial biopsy.

BACKGROUND: Histopathologic criteria for grading of acute cardiac allograft rejection are focused on the most severe lesion that is recognized among the myocardial fragments provided by each endomyocardial biopsy specimen. Considering the distribution of rejection lesions among all the fragments improved the accuracy in characterizing the severity of rejection in pathologic studies. This study was undertaken to verify the usefulness of a semiquantitative evaluation of endomyocardial biopsy specimens, consisting of the calculation of the proportion of fragments showing rejection in the clinical setting. METHODS: Of the 2386 biopsy specimens obtained during the first posttransplantation year in 168 consecutive cardiac allograft recipients, 290 biopsy specimens constituted by > or = 3 adequate fragments and showing rejection not followed by treatment (n = 159) or being the first biopsy specimen prompting treatment with augmented immunosuppression for that rejection episode (n = 131) were selected. These biopsy specimens (index biopsy specimens) were grouped according to whether rejection was present in < or = 33%, > 33% to < or = 67%, and > 67% of the fragments. The rejection grade (according to the standardized grading system) and the proportion of fragments positive for rejection were correlated with the occurrence of clinical symptoms and signs of rejection at index biopsy and with the results of the next biopsy. RESULTS: Rejections graded > or = 3A were more frequently symptomatic (36% vs 9% for those graded < 3, p < 0.0001), as were those involving increasing proportions of fragments (< or = 33%: 5 of 124, 4%; > 33 to < or = 67%: 13 of 99, 13%; > 67%: 19 of 67, 28% [p < 0.0001]). Spontaneous resolution after untreated biopsies was more frequent in focal (grade 1A and 2) than in diffuse mild (1B) rejections (68% vs 38% [p < 0.04]), whereas progression to grade 3A or greater was less frequent (4% vs 27% [p < 0.01]). Increasing proportions of positive fragments were associated with lower frequencies of spontaneous resolution (p < 0.05) and higher frequencies of worsening (9%, 22%, 43% [p < 0.009]) or progression to grade 3A or greater (2%, 6%, 28% [p < 0.005]). Complete resolution after treatment was less frequent for increasing proportions of positive fragments at index biopsy (80%, 66%, 49% [p < 0.05]). CONCLUSIONS: Diffuse versus focal rejection pattern and the proportion of positive fragments seem to be clinically relevant in terms of occurrence of symptoms, spontaneous evolution, and response to treatment.

Causes of late failure after heart transplantation: a ten-year survey.

BACKGROUND: Little is known about the causes of death of heart transplant recipients who survive long-term. METHODS: The pathologic and clinical records of 97 patients who underwent heart transplantation in Italy from 1985 to 1995 and died (85 of 97) or underwent retransplantation (12 of 97) at least 2 years after transplantation were surveyed. Graft failures were classified as late (occurring between 2 and 5 years after transplantation) and belated (more than 5 years). RESULTS: Graft vasculopathy was the single most common cause of death (40.0%) and the only cause of late retransplantation. Tumors ranked second (23.5% of deaths), but the expected non-Hodgkin's lymphomas and Kaposi's sarcoma were accompanied by a high number of lung cancers (especially metastasizing adenocarcinomas). They were followed by the emergence or recurrence of pretransplantation diseases (9.4%), fatal infections (exclusively bacterial) (4.7%), the development of transmissible diseases (viral hepatitis and acquired immunodeficiency syndrome, 4.7%), and late acute rejection (2.3%). The distribution of failures differed in the late and belated periods: death and organ loss proportions for graft vasculopathy, respectively, fell and rose from the late to the belated period; some types of malignancy and fatal acute rejection were never observed in the belated period, whereas the emergence of pretransplantation diseases prevailed in the belated period. Graft vasculopathy was more frequent and tumors were less frequent among patients undergoing transplantation for ischemic heart disease. CONCLUSIONS: The reasons why heart transplant recipients die or undergo retransplantation, respectively, in the late and belated periods slightly differ from one another and are widely different than in short-term survivors.

Acute myocardial infarction in humans is associated with activation of programmed myocyte cell death in the surviving portion of the heart.

Conditions of diastolic overload associated with increases in filling pressure trigger apoptosis. Moreover, ischemia alone and ischemia followed by reperfusion induce programmed cell death in myocytes in vitro. On this basis, the possibility was raised that apoptotic myocyte cell death may occur in the surviving myocardium acutely after infarction. Myocardial samples were obtained from the region adjacent to and remote from infarction in patients who died within 10 days from the initial clinical symptoms. Apoptosis was measured quantitatively by the terminal deoxynucleotidyl transferase assay and confirmed biochemically by DNA extraction and agarose gel electrophoresis. This analysis included 20 infarcted and ten control hearts. DNA strand breaks in myocyte nuclei were observed in all 20 infarcted hearts in both the regions bordering on and distant from the necrotic myocardium. However, the number of apoptotic nuclei was greater in the peri-infarcted region than in that away from infarction. Quantitatively, 12% of myocytes in the border zone showed DNA strand breaks, whereas 1% of cells were undergoing apoptosis in the remote myocardium. Moreover DNA laddering was detected biochemically in these two regions of the heart. Thus, apoptosis appears to be a significant complicating factor of acute myocardial infarction increasing the magnitude of myocyte cell death associated with coronary artery occlusion.

Significance of pericardial effusion after heart transplantation.

The aim of this study was to evaluate the clinical significance of pericardial effusion after heart transplantation and to assess its correlation with acute rejection. One hundred fifty transplanted patients were followed up for the first year: serial echocardiographic studies were performed on the same day as were the endomyocardial biopsies; hemodynamic studies and coronary angiographies were performed 1 year after transplant. Ten days after surgery, pericardial effusion was absent in 77 patients, small in 52, moderate in 14, and large in 7, and was significantly related to severe postoperative bleeding (p < 0.001). Patients were classified according to the presence and the course of pericardial effusion in group A (absence or disappearance of previous pericardial effusion within 1 month, 107 patients) and in group B (onset, persistence, or increase in pericardial effusion, 43 patients). One hundred nineteen patients experienced > or = 1 acute rejection episode. The evolution of pericardial effusion was different (p < 0.0001) according to the number of acute rejection episodes and biopsy specimens showing acute rejection, histologic grading and time of the first episode, and histologic grading of the most severe acute rejection episode. Furthermore, there was a significant correlation with the cumulative duration of acute rejection episodes (p < 0.005) and the presence of previous cardiac surgical history (p < 0.007), but no correlation with cardiac transplant vasculopathy or with a positive weight mismatch. This study suggests that pericardial effusion in transplant recipients is associated with a higher incidence and more severe histologic grading of acute rejection episodes; its presence indicates the need for stricter monitoring of acute rejection.