Self-Assembled Fluorinated Nanoparticles as Sensitive and Biocompatible Theranostic Platforms for 19 F MRI.

Theranostics is a novel paradigm integrating therapy and diagnostics, thereby providing new prospects for overcoming the limitations of traditional treatments. In this context, perfluorocarbons (PFCs) are the most widely used tracers in preclinical fluorine-19 magnetic resonance (19 F MR), primarily for their high fluorine content. However, PFCs are extremely hydrophobic, and their solutions often display reduced biocompatibility, relative instability, and subpar 19 F MR relaxation times. This study aims to explore the potential of micellar 19 F MR imaging (MRI) tracers, synthesized by polymerization-induced self-assembly (PISA), as alternative theranostic agents for simultaneous imaging and release of the non-steroidal antileprotic drug clofazimine. In vitro, under physiological conditions, these micelles demonstrate sustained drug release. In vivo, throughout the drug release process, they provide a highly specific and sensitive 19 F MRI signal. Even after extended exposure, these fluoropolymer tracers show biocompatibility, as confirmed by the histological analysis. Moreover, the characteristics of these polymers can be broadly adjusted by design to meet the wide range of criteria for preclinical and clinical settings. Therefore, micellar 19 F MRI tracers display physicochemical properties suitable for in vivo imaging, such as relaxation times and non-toxicity, and high performance as drug carriers, highlighting their potential as both diagnostic and therapeutic tools.

Novel transcriptomic signatures associated with premature kidney allograft failure.

BACKGROUND: The power to predict kidney allograft outcomes based on non-invasive assays is limited. Assessment of operational tolerance (OT) patients allows us to identify transcriptomic signatures of true non-responders for construction of predictive models. METHODS: In this observational retrospective study, RNA sequencing of peripheral blood was used in a derivation cohort to identify a protective set of transcripts by comparing 15 OT patients (40% females), from the TOMOGRAM Study (NCT05124444), 14 chronic active antibody-mediated rejection (CABMR) and 23 stable graft function patients ≥15 years (STA). The selected differentially expressed transcripts between OT and CABMR were used in a validation cohort (n = 396) to predict 3-year kidney allograft loss at 3 time-points using RT-qPCR. FINDINGS: Archetypal analysis and classifier performance of RNA sequencing data showed that OT is clearly distinguishable from CABMR, but similar to STA. Based on significant transcripts from the validation cohort in univariable analysis, 2 multivariable Cox models were created. A 3-transcript (ADGRG3, ATG2A, and GNLY) model from POD 7 predicted graft loss with C-statistics (C) 0.727 (95% CI, 0.638-0.820). Another 3-transcript (IGHM, CD5, GNLY) model from M3 predicted graft loss with C 0.786 (95% CI, 0.785-0.865). Combining 3-transcripts models with eGFR at POD 7 and M3 improved C-statistics to 0.860 (95% CI, 0.778-0.944) and 0.868 (95% CI, 0.790-0.944), respectively. INTERPRETATION: Identification of transcripts distinguishing OT from CABMR allowed us to construct models predicting premature graft loss. Identified transcripts reflect mechanisms of injury/repair and alloimmune response when assessed at day 7 or with a loss of protective phenotype when assessed at month 3. FUNDING: Supported by the Ministry of Health of the Czech Republic under grant NV19-06-00031.

A novel prognostic nomogram predicts premature failure of kidney allografts with IgA nephropathy recurrence.

BACKGROUND: Recurrence of immunoglobulin A nephropathy (IgAN) limits graft survival in kidney transplantation. However, predictors of a worse outcome are poorly understood. METHODS: Among 442 kidney transplant recipients (KTRs) with IgAN, 83 (18.8%) KTRs exhibited biopsy-proven IgAN recurrence between 1994 and 2020 and were enrolled in the derivation cohort. A multivariable Cox model predicting allograft loss based on clinical data at the biopsy and a web-based nomogram were developed. The nomogram was externally validated using an independent cohort (n = 67). RESULTS: Patient age <43 years {hazard ratio [HR] 2.20 [95% confidence interval (CI) 1.41-3.43], P < .001}, female gender [HR 1.72 (95% CI 1.07-2.76), P = .026] and retransplantation status [HR 1.98 (95% CI 1.13-3.36), P = .016] were identified as independent risk factors for IgAN recurrence. Patient age <43 years [HR 2.77 (95% CI 1.17-6.56), P = .02], proteinuria >1 g/24 hours [HR 3.12 (95% CI 1.40-6.91), P = .005] and C4d positivity [HR 2.93 (95% CI 1.26-6.83), P = .013] were found to be associated with graft loss in patients with IgAN recurrence. A nomogram predicting graft loss was constructed based on clinical and histological variables, with a C statistic of 0.736 for the derivation cohort and 0.807 for the external validation cohort. CONCLUSIONS: The established nomogram identified patients with recurrent IgAN at risk for premature graft loss with good predictive performance.

Inflammation and fibrosis characterize different stages of myocardial remodeling in patients after stereotactic body radiotherapy of ventricular myocardium for recurrent ventricular tachycardia.

We performed a histological and immunohistochemical analysis of myocardia from 3 patients who underwent radiosurgery and died for various reasons 3 months to 9 months after radiotherapy. In Case 1 (death 3 months after radiotherapy) we observed a sharp transition between relatively intact and irradiated regions. In the myolytic foci, only scattered cardiomyocytes were left and the area was infiltrated by immune cells. Using immunohistochemistry we detected numerous inflammatory cells including CD68+/CD11c+ macrophages, CD4+ and CD8+ T-lymphocytes and some scattered CD20+ B-lymphocytes. Mast cells were diminished in contrast to viable myocardium. In Case 2 and Case 3 (death 6 and 9 months after radiotherapy, respectively) we found mostly fibrosis, infiltration by adipose tissue and foci of calcification. Inflammatory infiltrates were less pronounced. Our observations are in accordance with animal experimental studies and confirm a progress from myolysis to fibrosis. In addition, we demonstrate a role of pro-inflammatory macrophages in the earlier stages of myocardial remodeling after stereotactic radioablation for ventricular tachycardia.

Verrucous Skin Lesions on the Feet in Diabetic Neuropathy in the Context of Podiatric Practice - Our Pilot Experiences.

Skin changes in patients with diabetic foot (DF) are relatively common. The most frequent lesions feature papillae or cilia of various forms. The condition known as "verrucous skin lesions on the feet in diabetic neuropathy" (VSLDN) occurs in patients with distal diabetic sensorimotor neuropathy and is commonly located in places of high mechanical pressure. However, there is a scarcity of published data on the diagnosis and treatment of VSLDN. Our paper describes various types of VSLDN skin pathology, summarizes the diagnostic procedure options available, and documents the experience of our diabetic foot clinic in applying short-term VSLDN therapies as part of routine podiatric practice.

Vascular Remodeling of Clinically Used Patches and Decellularized Pericardial Matrices Recellularized with Autologous or Allogeneic Cells in a Porcine Carotid Artery Model.

Background: Cardiovascular surgery is confronted by a lack of suitable materials for patch repair. Acellular animal tissues serve as an abundant source of promising biomaterials. The aim of our study was to explore the bio-integration of decellularized or recellularized pericardial matrices in vivo. Methods: Porcine (allograft) and ovine (heterograft, xenograft) pericardia were decellularized using 1% sodium dodecyl sulfate ((1) Allo-decel and (2) Xeno-decel). We used two cell types for pressure-stimulated recellularization in a bioreactor: autologous adipose tissue-derived stromal cells (ASCs) isolated from subcutaneous fat of pigs ((3) Allo-ASC and (4) Xeno-ASC) and allogeneic Wharton's jelly mesenchymal stem cells (WJCs) ((5) Allo-WJC and (6) Xeno-WJC). These six experimental patches were implanted in porcine carotid arteries for one month. For comparison, we also implanted six types of control patches, namely, arterial or venous autografts, expanded polytetrafluoroethylene (ePTFE Propaten® Gore®), polyethylene terephthalate (PET Vascutek®), chemically stabilized bovine pericardium (XenoSure®), and detoxified porcine pericardium (BioIntegral® NoReact®). The grafts were evaluated through the use of flowmetry, angiography, and histological examination. Results: All grafts were well-integrated and patent with no signs of thrombosis, stenosis, or aneurysm. A histological analysis revealed that the arterial autograft resembled a native artery. All other control and experimental patches developed neo-adventitial inflammation (NAI) and neo-intimal hyperplasia (NIH), and the endothelial lining was present. NAI and NIH were most prominent on XenoSure® and Xeno-decel and least prominent on NoReact®. In xenografts, the degree of NIH developed in the following order: Xeno-decel > Xeno-ASC > Xeno-WJC. NAI and patch resorption increased in Allo-ASC and Xeno-ASC and decreased in Allo-WJC and Xeno-WJC. Conclusions: In our setting, pre-implant seeding with ASC or WJC had a modest impact on vascular patch remodeling. However, ASC increased the neo-adventitial inflammatory reaction and patch resorption, suggesting accelerated remodeling. WJC mitigated this response, as well as neo-intimal hyperplasia on xenografts, suggesting immunomodulatory properties.

Do low GDP neutral pH solutions prevent or retard peritoneal membrane alterations in long-term peritoneal dialysis?

Several studies have been published in the last decade on the effects of low glucose degradation product (GDP) neutral pH (L-GDP/N-pH) dialysis solutions on peritoneal morphology and function during the long-term PD treatment. Compared to conventional solutions, the impact of these solutions on the morphological and functional alterations of the peritoneal membrane is discussed, including those of effluent proteins that reflect the status of peritoneal tissues. Long-term PD with conventional solutions is associated with the loss of mesothelium, submesothelial and interstitial fibrosis, vasculopathy, and deposition of advanced glycosylation end products (AGEs). L-GDP/N-pH solutions mitigate these alterations, although vasculopathy and AGE deposition are still present. Increased vascular density was found in some studies. Small solute transport increases with PD duration on conventional solutions. Initially, higher values are present on L-GDP/N-pH treatment, but these may be reversible and remain stable with PD duration. Consequently, ultrafiltration (UF) is lower initially but remains stable thereafter. At 5 years, UF and small pore fluid transport are higher, while free water transport decreased only slightly during follow-up. Cancer antigen 125 was initially higher on L-GDP/N-pH solutions, suggesting better mesothelial preservation but decreased during follow-up. Therefore, L-GDP/N-pH solutions may not prevent but reduce and retard the peritoneal alterations induced by continuous exposure to glucose-based dialysis fluids.

Intimal Arteritis and Microvascular Inflammation Are Associated With Inferior Kidney Graft Outcome, Regardless of Donor-Specific Antibodies.

Background: The prognostic role of intimal arteritis of kidney allografts in donor-specific antibody negative (DSA-) antibody-mediated rejection (ABMR) remains unclear. Methods: Seventy-two out of 881 patients who had undergone kidney transplantation from 2014 to 2017 exhibited intimal arteritis in biopsies performed during the first 12 months. In 26 DSA negative cases, the intimal arteritis was accompanied by tubulointerstitial inflammation as part of T cell-mediated vascular rejection (TCMRV, N = 26); intimal arteritis along with microvascular inflammation occurred in 29 DSA negative (ABMRV/DSA-) and 19 DSA positive cases (ABMRV, DSA+, N = 17). In 60 (83%) patients with intimal arteritis, the surveillance biopsies after antirejection therapy were performed. Hundred and two patients with non-vascular ABMR with DSA (ABMR/DSA+, N = 55) and without DSA (ABMR/DSA-, N = 47) served as controls. Time to transplant glomerulopathy (TG) and graft failure were the study endpoints. Results: Transplant glomerulopathy -free survival at 36 months was 100% in TCMRV, 85% in ABMR/DSA-, 65% in ABMRV/DSA-, 54% in ABMR/DSA+ and 31% in ABMRV/DSA+ (log rank p < 0.001). Death-censored graft survival at 36 months was 98% in ABMR/DSA-, 96% in TCMRV, 86% in ABMRV/DSA-, 79% in ABMR/DSA+, and 64% in ABMRV/DSA+ group (log rank p = 0.001). In surveillance biopsies, the resolution of rejection was found in 19 (90%) TCMRV, 14 (58%) ABMRV/DSA-, and only 4 (27%) ABMRV/DSA+ patients (p = 0.006). In the multivariable model, intimal arteritis as part of ABMR represented a significant risk for TG development (HR 2.1, 95% CI 1.2-3.8; p = 0.012) regardless of DSA status but not for graft failure at 36 months. Conclusions: Intimal arteritis as part of ABMR represented a risk for early development of TG regardless of the presence or absence of DSA. Intimal arteritis in DSA positive ABMR represented the high-risk phenotype.

Radiation-Induced Changes in Ventricular Myocardium After Stereotactic Body Radiotherapy for Recurrent Ventricular Tachycardia.

Stereotactic body radiotherapy (SBRT) has been suggested as a promising therapeutic alternative in cases of failed catheter ablation for recurrent ventricular tachycardias (VTs) in patients with structural heart disease. This case series is the first postmortem immunohistochemical analysis of morphologic changes in the myocardium early and late after SBRT. The present findings are in line with experimental observations on apoptosis followed by fibrosis. This may explain why the effect of SBRT on VT is not predominantly immediate. Together with observation of early recurrences after SBRT for VT, these data suggest that this strategy may have rather delayed antiarrhythmic effects.

Chronic Active Antibody-Mediated Rejection Is Associated With the Upregulation of Interstitial But Not Glomerular Transcripts.

Molecular assessment of renal allografts has already been suggested in antibody-mediated rejection (ABMR), but little is known about the gene transcript patterns in particular renal compartments. We used laser capture microdissection coupled with quantitative RT-PCR to distinguish the transcript patterns in the glomeruli and tubulointerstitium of kidney allografts in sensitized retransplant recipients at high risk of ABMR. The expressions of 13 genes were quantified in biopsies with acute active ABMR, chronic active ABMR, acute tubular necrosis (ATN), and normal findings. The transcripts were either compartment specific (TGFB1 in the glomeruli and HAVCR1 and IGHG1 in the tubulointerstitium), ABMR specific (GNLY), or follow-up specific (CXCL10 and CX3CR1). The transcriptional profiles of early acute ABMR shared similarities with ATN. The transcripts of CXCL10 and TGFB1 increased in the glomeruli in both acute ABMR and chronic active ABMR. Chronic active ABMR was associated with the upregulation of most genes (SH2D1B, CX3CR1, IGHG1, MS4A1, C5, CD46, and TGFB1) in the tubulointerstitium. In this study, we show distinct gene expression patterns in specific renal compartments reflecting cellular infiltration observed by conventional histology. In comparison with active ABMR, chronic active ABMR is associated with increased transcripts of tubulointerstitial origin.

Three-month course of intragraft transcriptional changes in kidney allografts with early histological minimal injury - a cohort study.

The tubulitis with/without interstitial inflammation not meeting criteria for T-cell-mediated rejection (minimal allograft injury) is the most frequent histological findings in early transplant biopsies. The course of transcriptional changes in sequential kidney graft biopsies has not been studied yet. Molecular phenotypes were analyzed using the Molecular Microscope® Diagnostic System (MMDx) in 46 indication biopsies (median 13 postoperative days) diagnosed as minimal allograft injury and in corresponding follow-up biopsies at 3 months. All 46 patients with minimal injury in early biopsy received steroid pulses. MMDx interpreted indication biopsies as no-rejection in 34/46 (74%), T-cell-mediated rejection (TCMR) in 4/46 (9%), antibody-mediated rejection in 6/46 (13%), and mixed rejection in 2/46 (4%) cases. Follow-up biopsies were interpreted by MMDx in 37/46 (80%) cases as no-rejection, in 4/46 (9%) as TCMR, and in 5/46 (11%) as mixed rejection. Follow-up biopsies showed a decrease in MMDx-assessed acute kidney injury (P = 0.001) and an increase of atrophy-fibrosis (P = 0.002). The most significant predictor of MMDx rejection scores in follow-up biopsies was the tubulitis classifier score in initial biopsies (AUC = 0.84, P = 0.002), confirmed in multivariate binary regression (OR = 16, P = 0.016). Molecular tubulitis score at initial biopsy has the potential to discriminate patients at risk for molecular rejection score at follow-up biopsy.

Molecular patterns of isolated tubulitis differ from tubulitis with interstitial inflammation in early indication biopsies of kidney allografts.

The Banff 2019 kidney allograft pathology update excluded isolated tubulitis without interstitial inflammation (ISO-T) from the category of borderline (suspicious) for acute T cell-mediated rejection due to its proposed benign clinical outcome. In this study, we explored the molecular assessment of ISO-T. ISO-T or interstitial inflammation with tubulitis (I + T) was diagnosed in indication biopsies within the first 14 postoperative days. The molecular phenotype of ISO-T was compared to I + T either by using RNA sequencing (n = 16) or by Molecular Microscope Diagnostic System (MMDx, n = 51). RNA sequencing showed lower expression of genes related to interferon-y (p = 1.5 *10-16), cytokine signaling (p = 2.1 *10-20) and inflammatory response (p = 1.0*10-13) in the ISO-T group than in I + T group. Transcripts with increased expression in the I + T group overlapped significantly with previously described pathogenesis-based transcript sets associated with cytotoxic and effector T cell transcripts, and with T cell-mediated rejection (TCMR). MMDx classified 25/32 (78%) ISO-T biopsies and 12/19 (63%) I + T biopsies as no-rejection. ISO-T had significantly lower MMDx scores for interstitial inflammation (p = 0.014), tubulitis (p = 0.035) and TCMR (p = 0.016) compared to I + T. Fewer molecular signals of inflammation in isolated tubulitis suggest that this is also a benign phenotype on a molecular level.

Sirolimus vs mycophenolate mofetil (MMF) in primary combined pancreas and kidney transplantation. Results of a long-term prospective randomized study.

The study was intended to compare pancreas graft survival rates in two groups of pancreas and kidney transplant recipients prospectively randomized to treatment either with sirolimus or MMF. From 2002 to 2013, 238 type 1 diabetic recipients with end-stage kidney disease were randomized 1:1 to sirolimus or MMF treatment. Noncensored pancreas survival at 5 years was 76.4 and 71.6% for sirolimus and MMF groups, respectively (P > .05). Death-censored pancreas survival was better in the sirolimus group (P = .037). After removal of early graft losses pancreas survival did not differ between groups (MMF 83.1% vs sirolimus 91.6%, P = .11). Nonsignificantly more grafts were lost due to rejection in the MMF group (10 vs 5; P = .19). Cumulative patient 5-year survival was 96% in the MMF group and 91% in the sirolimus group (P > .05). Five-year cumulative noncensored kidney graft survival rates did not statistically differ (85.6% in the sirolimus group and 88.8% in MMF group). Recipients treated with MMF had significantly more episodes of gastrointestinal bleeding (7 vs 0, P = .007). More recipients in the sirolimus group required corrective surgery due to incisional hernias (21 vs 12, P = .019). ClinicalTrials No.: NCT03582878.

Preserved Expression of Skin Neurotrophic Factors in Advanced Diabetic Neuropathy Does Not Lead to Neural Regeneration despite Pancreas and Kidney Transplantation.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes with potential severe consequences. Its pathogenesis involves hyperglycemia-linked mechanisms, which may include changes in the expression of neurotrophic growth factors. We analyzed the expression of 29 factors potentially related to nerve degeneration and regeneration in skin biopsies from 13 type 1 diabetic pancreas and kidney recipients with severe DPN including severe depletion of intraepidermal nerve fibers (IENF) in lower limb skin biopsies (group Tx1 1st examination). The investigation was repeated after a median 28-month period of normoglycemia achieved by pancreas transplantation (group Tx1 2nd examination). The same tests were performed in 13 stable normoglycemic pancreas and kidney recipients 6-12 years posttransplantation (group Tx2), in 12 matched healthy controls (group HC), and in 12 type 1 diabetic subjects without severe DPN (group DM). Compared to DM and HC groups, we found a significantly higher (p < 0.05-0.001) expression of NGF (nerve growth factor), NGFR (NGF receptor), NTRK1 (neurotrophic receptor tyrosine kinase 1), GDNF (glial cell-derived neurotrophic factor), GFRA1 (GDNF family receptor alpha 1), and GFAP (glial fibrillary acidic protein) in both transplant groups (Tx1 and Tx2). Enhanced expression of these factors was not normalized following the median 28-month period of normoglycemia (Tx1 2nd examination) and negatively correlated with IENF density and with electrophysiological indices of DPN (vibration perception threshold, electromyography, and autonomic tests). In contrast to our expectation, the expression of most of 29 selected factors related to neural regeneration was comparable in subjects with severe peripheral nerve fiber depletion and healthy controls and the expression of six factors was significantly upregulated. These findings may be important for better understanding the pathophysiology of nerve regeneration and for the development of intervention strategies.

A Complex Heart Team's Approach to a Patient With Giant Cell Myocarditis.

Giant cell myocarditis is known as a rare and frequently fatal type of myocarditis that is usually characterized by progressive congestive heart failure and frequent ventricular arrhythmias. We report a rare case of giant cell myocarditis in a 64-year-old previously healthy woman. The case was complicated by the rapid development of progressive acute heart failure, which required the comprehensive care of our heart team. Using a broad spectrum of therapeutic approaches, the patient successfully underwent heart transplantation.

Successful Posaconazole Therapy of Disseminated Alternariosis due to Alternaria infectoria in a Heart Transplant Recipient.

We report a case of phaeohyphomycosis caused by Alternaria infectoria in a 61-year-old heart transplant recipient with multiple skin lesions and pulmonary infiltrates. The infection spread via the haematogenous route from the primary cutaneous lesions into the lungs. The diagnosis was based on the histopathological examination, direct microscopy, skin lesion cultures and detection of Alternaria DNA in the bronchoalveolar lavage fluid using molecular methods. The treatment consisted of a combination of surgical excision and systemic antifungal therapy. Voriconazole was the first agent used but had a weak effect. Posaconazole was subsequently used to achieve a successful response. The isolate was identified as A. infectoria by sequencing of the rDNA ITS region and the partial ß-tubulin gene.

Combining Donor Characteristics with Immunohistological Data Improves the Prediction of Islet Isolation Success.

Variability of pancreatic donors may significantly impact the success of islet isolation. The aim of this study was to evaluate donor factors associated with isolation failure and to investigate whether immunohistology could contribute to organ selection. Donor characteristics were evaluated for both successful (n = 61) and failed (n = 98) islet isolations. Samples of donor pancreatic tissue (n = 78) were taken for immunohistochemical examination. Islet isolations with 250000 islet equivalents were considered successful. We confirmed that BMI of less than 25 kg/m2 (P < 0.001), cold ischemia time more than 8 hours (P < 0.01), hospitalization longer than 96 hours (P < 0.05), higher catecholamine doses (P < 0.05), and edematous pancreases (P < 0.01) all unfavorably affected isolation outcome. Subsequent immunohistochemical examination of donor pancreases confirmed significant differences in insulin-positive areas (P < 0.001). ROC analyses then established that the insulin-positive area in the pancreas could be used to predict the likely success of islet isolation (P < 0.001). At the optimal cutoff point (>1.02%), sensitivity and specificity were 89% and 76%, respectively. To conclude, while the insulin-positive area, determined preislet isolation, as a single variable, is sufficient to predict isolation outcome and helps to improve the success of this procedure, its combination with the established donor scoring system might further improve organ selection.

Novel insights into pretransplant allosensitization in heart transplant recipients in the contemporary era of immunosuppression and rejection surveillance.

Solid-phase assays (SPA) have facilitated detection and definition of antibodies to human leukocyte antigens (HLA) and major histocompatibility complex class I chain-related antigen A (MICA). However, clinical consequences of pretransplant SPA results in heart transplantation have been studied insufficiently in the current era of immunosuppression and rejection surveillance. Pretransplant sera, panel-reactive antibodies (PRA), pretransplant crossmatch, and clinical data were retrospectively analyzed in 264 adult heart transplant recipients. The specificity of HLA and MICA antibodies and C1q-binding activity of donor-specific antibodies (DSA) were defined using SPA. Pretransplant HLA antibodies were detected in 57 (22%) individuals, in 28 individuals (11%); these antibodies were DSA after transplant. Preformed DSA and elevated peak PRA were independent predictors of pathologic AMR, which occurred in 19 individuals (7%). The increasing number of DSA and the cumulative mean fluorescence intensity of DSA were associated with AMR. C1q-binding assay was a suboptimal predictor of AMR in our cohort. Pretransplant allosensitization and MICA antibodies were related neither to impaired graft survival nor to other adverse clinical events during a median follow-up of 39 months. Identification of preformed DSA by SPA, in addition to PRA monitoring, may predict AMR in the contemporary era of heart transplantation.

Tricuspid valve surgery in patients with idiopathic hypereosinophilic syndrome.

A 53-year-old female with idiopathic hypereosinophilic syndrome underwent recurrent tricuspid valve replacement for Löffler's endocarditis. We review the literature on tricuspid valve surgery in patients with this uncommon disorder.