Stable Graft Research Articles

Covalent Conjugation of Small Molecule Inhibitors and Growth Factors to a Silk Fibroin-Derived Bioink to Develop Phenotypically Stable 3D Bioprinted Cartilage.

Implantation of a phenotypically stable cartilage graft could represent a viable approach for repairing osteoarthritic (OA) cartilage lesions. In the present study, we investigated the effects of modulating the bone morphogenetic protein (BMP), transforming growth factor beta (TGFβ), and interleukin-1 (IL-1) signaling cascades in human bone marrow stromal cell (hBMSC)-encapsulated silk fibroin gelatin (SF-G) bioink. The selected small molecules LDN193189, TGFβ3, and IL1 receptor antagonist (IL1Ra) are covalently conjugated to SF-G biomaterial to ensure sustained release, increased bioavailability, and printability, confirmed by ATR-FTIR, release kinetics, and rheological analyses. The 3D bioprinted constructs with chondrogenically differentiated hBMSCs were incubated in an OA-inducing medium for 14 days and assessed through a detailed qPCR, immunofluorescence, and biochemical analyses. Despite substantial heterogeneity in the observations among the donors, the IL1Ra molecule illustrated the maximum efficiency in enhancing the expression of articular cartilage components, reducing the expression of hypertrophic markers (re-validated by the GeneMANIA tool), as well as reducing the production of inflammatory molecules by the hBMSCs. Therefore, this study demonstrated a novel strategy to develop a chemically decorated, printable and biomimetic SF-G bioink to produce hyaline cartilage grafts resistant to acquiring OA traits that can be used for the treatment of degenerated cartilage lesions.

Number of intra-operative cyclic knee motion required to achieve stable graft tension in anterior cruciate ligament reconstruction; a prospective clinical study.

Applying pretension by cyclic knee motion immediately before graft fixation in anterior cruciate ligament (ACL) reconstruction surgery decreases graft elongation during the postoperative course. However, the expected change in graft tension caused by cyclic knee motion remains unclear. We measured graft tension changes caused by cyclic knee motion during double-bundle ACL reconstruction. We included 39 patients undergoing primary anatomical double-bundle ACL reconstruction with autologous hamstrings as graft sources, at multiple centers between February 2021 and August 2022. After securing the anteromedial (AM) and posterolateral (PL) bundle grafts to the femoral cortex, they were initially tensioned to 40 N per bundle. After 10 cycles of knee extension and flexion motion, ranging from 0 to 90-110°, tension was re-measured and re-tensioned to 40 N if the graft tension had decreased. This was repeated thrice for 10 cycles on each graft. Every 10 cycles, we recorded graft tension changes (ΔGT) and compared the mean ΔGT in the AM and PL bundles. Furthermore, we assessed relationships between total ΔGT in each bundle, age, sex, and graft diameter. Twenty-five women and 14 men with a mean age of 27.4 ± 12.4 years were included. The mean ΔGT in AM and PL bundles after every 10 cycles were 6.6 ± 3.7 N, 3.0 ± 2.3 N, 1.4 ± 1.5 N, and 9.9 ± 3.8 N, 4.9 ± 2.6 N, and 2.5 ± 1.9 N, respectively. There were significant differences in ΔGT in both bundles after every 10 cycles (p < 0.01). ΔGT in the AM bundle was significantly lower than in the PM bundle at the same number of cycles (p < 0.01). No correlation was observed between ΔGT in either bundle and age, sex, or graft diameter. The initially applied graft tension decreased by intra-operative cyclic knee movement, and the changes in graft tension decreased after retention and repeated cycles. Three sets of 10 cycles knee motion may avoid initial tension loss of the hamstring autograft in the early phase after double-bundle ACL reconstruction.

Sequence of Surgical Approach in a Patient with Autosomal Dominant Polycystic Kidney Disease Treated with Renal Transplantation

Introduction: Describe the surgical sequence in a 55-year-old woman with an Autosomal Dominant Polycystic Kidney (ADPKD) Case Presentation: We performed three surgical procedures in a woman with Chronic Kidney Disease (CKD) secondary to ADPKD of 13 years of evolution from June to November 2023 which are as follows: Resection of 2 liver cysts and Laparoscopic cholecystectomy, Related living donor renal transplant, and Bilateral open nephrectomy, all of them with the use of innovative technology. Result: The first procedure was performed for risk reduction and two cysts of 3.5 cm x 1.6 cm x 1.5 cm and 3.3 cm x 2.0 cm x 1.4 cm and chronic cholecystitis were reported. The second one was performed one month later; the patient had previous creatinine values of 4.73. The graft was positioned in the right iliac fossa where end-to-side anastomosis of renal vessels was performed with external iliac vessels and uretero-vesical anastomosis was executed with the Lich-Gregoir technique; the total ischemia time was 109 minutes and the kidney presented immediate function. At 48 hours, a Doppler ultrasound was performed, which reported a renal artery resistance index of 0.5, with homogeneous cortical perfusion, without collections, vessels, and ureter without stenosis or thrombosis; therefore, the patient was discharged 5 days after the transplant with optimal graft function and creatinine levels of 1.75. In the last procedure, two kidneys of 1.6 kg each were obtained and pathology reported adult polycystic disease with interstitial fibrosis, chronic inflammation, dystrophic calcification, tubular and glomerular atrophy. At the moment she has stable graft function and went from having creatinine levels of 4.73 to 1.2 and her glomerular filtration rate went from 9.68 to 50.84.

Cell cycle arrest biomarkers for the early detection of acute allograft dysfunction and acute rejection in living donor kidney transplantation: a cross-sectional study from Egypt.

Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are G1 cell arrest biomarkers that have demonstrated accuracy and validity in predicting and diagnosing acute kidney injury (AKI). This study aimed to evaluate the validity of [TIMP-2]×[IGFBP7] in diagnosing acute allograft dysfunction and its utility in distinguishing acute rejection (AR) from nonrejection causes in kidney transplantation. This study included 48 adult living donor kidney transplant recipients (KTRs; 18 with AR, 15 with nonrejection causes of AKI, and 15 with stable grafts). Urinary TIMP-2 and IGFBP7 were measured, and [TIMP-2]×[IGFBP7] was calculated in all subjects. IGFBP7, TIMP-2, and [TIMP-2]×[IGFBP7] were statistically significantly higher in KTRs with acute allograft dysfunction than in those with stable grafts. [TIMP-2]×[IGFBP7] was statistically significantly higher in KTRs with AR than in those with nonrejection AKI. [TIMP-2]×[IGFBP7] at a cutoff level of 0.278 (ng/mL)2/1,000 had an area under the curve (AUC) of 0.99 with a sensitivity of 100% and a specificity of 93.3% in diagnosing acute allograft dysfunction, while at a cutoff level of 0.803 (ng/mL)2/1,000 had an AUC of 0.939 with a sensitivity of 94.4% and a specificity of 83.3% in diagnosing AR. Besides its role in the early detection of acute allograft dysfunction, [TIMP-2]×[IGFBP7] may help to differentiate between AR and nonrejection causes in KTRs. However, whether and how urinary [TIMP-2]×[IGFBP7] can be used in clinical diagnosis still requires further research.

Changes in Cardiac Structure and Function Following Fistula Ligation in Kidney Transplant Recipients (Cohort Study)

Purpose: International guidelines recommend that haemodialysis access is provided by an arteriovenous fistula (AVF), which enables frequent, reliable access to the circulation, but there are no guidelines to suggest whether these AVFs need to be ligated after kidney transplantation. Cardiovascular morbidity and mortality remain high in recipients of a kidney transplant, the persistence of a patent arteriovenous fistula (AVF) after transplantation may contribute to ongoing maladaptive cardiovascular remodelling. The ability to reverse this maladaptive remodelling by ligation of this AVF is unknown. We conducted this trial to evaluate the effect of AVF ligation on cardiac structure and function in stable kidney transplant recipients. Also we studied the ability of preoperative echocardiographic and non-invasive hemodynamic measurements, including the effects of acute temporary occlusion of the fistula, to predict postoperative left ventricular diameter and mass reduction, by the closure of the fistula.&#x0D; Materials and Methods: Nonrandomized controlled trial. kidney transplant recipients (&gt;12 months after transplantation with stable graft function) were divided into 2 groups. The first referred for surgical arteriovenous fistula closure. The second group didn’t receive Fistula closure (control). Standard echocardiographic parameters, heart rate, and blood pressure were assessed preoperatively (fistula closure) at baseline. These measurements were repeated 6 months after surgical closure.&#x0D; Findings: Seventeen kidney transplant patients were prospectively studied with 11 case and 6 controls with no fistula closure. Surgical fistula closure decreased left ventricular end-diastolic diameter and mass indexes (29.9_2.4to 27.4_2.1 mm/m2, P&lt;0.001, and 141_37 to 132_39 g/m2, P&lt;0.05, respectively), whereas no changes were seen in controls after a similar delay. Postoperative left ventricular end-diastolic diameter and mass reductions correlated best with the increases in total peripheral resistance (r_0.85, P&lt;0.0001) and mean arterial blood pressure (r_0.64, P_0.006), respectively.&#x0D; Conclusions. Surgical closure of arteriovenous fistula reduces left ventricular diameter and mass in kidney transplant recipients. The best predictors of those morphological changes are the rise in blood pressure and total peripheral resistance induced by temporary occlusion of the fistula.&#x0D; Implications to Theory, Practice and Policy: Surgical closure of persistent AV fistula after renal transplantation to correct LV geometry and improve symptoms in terms of exertional dyspnea and palpitations.

Arteriolar hyalinization at 0-hour biopsy predicts long-term graft function in deceased kidney transplantation.

Regarding the relationship between donor kidney quality and renal graft function after deceased kidney transplantation (KTx) following donation after cardiac death (DCD), the evaluation timing varies depending on the study. Evaluation of histology and changes in long-term renal graft function is limited. A retrospective single-center study included 71 recipients who underwent 0-hour biopsy for KTx from DCD. The recipients were divided into two groups to evaluate factors related to renal graft function (study1). The two groups were categorized as stable graft function and poor graft function with the change of estimated glomerular filtration rate (eGFR) after KTx. The recipients were then divided into four groups to assess whether the factors identified in study1 were related to the change in long-term renal graft function (study2). They were categorized as follows: Improved, Stable, Deteriorated, and Primary non-function with the change of eGFR after KTx. In study1, donor age ≥ 50 years (29.5% vs. 65.2%; p = 0.09), banff arteriolar hyalinosis (ah) score (0.66 ± 0.78 vs. 1.2 ± 1.0; p = 0.018), and presence of glomerulosclerosis (43.2% vs. 76.2%; p = 0.017) were significant risk factors for poor long-term graft function. When the recipients were divided into four groups, the severity of ah correlated well with changes in long-term renal function. We can predict the shift in long-term renal graft function after KTx from DCD according to the severity of ah by 0-hour biopsy.

Simultaneous Tunnel Grafting and Anterior Cruciate Ligament Reconstructions Revision Using Double Suspensory Fixation: A Single-Stage Solution

The anterior cruciate ligament (ACL) is often vulnerable to sports-related injuries, leading to numerous ACL reconstructions (ACLRs) annually in the United States. Although largely successful, these procedures face the risk of recurrent instability due to graft failure. ACLR failures are typically attributed to technical errors and patient-related factors, with improper positioning of the tibial and femoral tunnels as the most common technical mistake. Current 2-stage revision techniques involve primary bone grafting followed by secondary tendon graft placement, resulting in increased costs and extended rehabilitation times. This article proposes a single-stage revision strategy involving simultaneous tunnel grafting and ACLR revision. The method employs double suspensory fixation by adjustable loop buttons, thereby eliminating the dependence on metaphyseal bone stock for stable graft fixation. This new procedure may offer a more efficient and cost-effective approach, reducing the need for a second surgery and potentially allowing patients to return to normal activities more quickly.

The Importance of 1-Year Protocol Biopsy in the Long-Term Prognosis of Kidney Transplants—5-Years Follow-Up

Protocol biopsies are performed to detect subclinical pathologies that may lead to future graft dysfunction. However, they are not routinely performed interventions in every transplant center. There is no established regimen for performing them. The study aimed to evaluate if protocol biopsies can improve long-term patient outcomes after detecting early disorders and modifying treatment. Our observational study included 61 patients who underwent protocol biopsy 12 months after the transplantation. Based on the biopsy results, patients with abnormal histologic material (n=37) were divided into 3 study groups as follows: patients with mild inflammatory lesions (n=21), patients with interstitial fibrosis and tubular atrophy (IFTA) grade II to III (n=12), and patients with BK virus nephropathy (n=4). The control group (n=24) included kidney recipients with IFTA 0 to I grade. Outcomes after 5-year follow-up were evaluated. Five years after the biopsy, patients in the control group had stable graft function (5-year change in serum creatinine was -0.09 mg/dL). An increase in serum creatinine levels was observed in patients with IFTA II to III compared with the control group (0.14 mg/dL, P=.04). Immunosuppressive treatment was modified in the group with mild inflammatory changes and in the BKV group after the biopsy result. In the group with mild inflammatory lesions, renal function was stable (change of serum creatinine was -0.01 mg/dL, P=.51). In the BKV nephropathy group, there was a significant reduction in serum creatine levels (-0.48 mg/dL, P=.016). The analysis showed no diagnostic value for serum creatinine concentration (95% CI 0.49-0.78, P=.08). Protocol biopsies are useful for detecting early pathologies and preventing allograft failure. They greatly benefit patients with detectable pathology that can be treated or in whom therapy modification is possible.

Novel transcriptomic signatures associated with premature kidney allograft failure

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. 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. 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. 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 month3. Supported by the Ministry of Health of the Czech Republic under grant NV19-06-00031.

Clinical, radiographic, and histological/histomorphometric analysis of maxillary sinus grafting with deproteinized porcine or bovine bone mineral: A randomized clinical trial.

The present study aimed to compare histomorphometrically evaluated new bone formation, radiographically measured graft stability, and clinical implant outcome between maxillary sinus grafting with either deproteinized porcine bone mineral (DPBM) or deproteinized bovine bone mineral (DBBM). Thirty maxillary sinuses were initially included and randomly assigned to the test group (TG; DPBM, n = 15) or control group (CG; DBBM, n = 15). After a healing period (6 months), axially retrieved bone biopsies of the molar region were used for histological/histomorphometric analysis of new bone formations. Additionally, radiographically measured graft stability and clinical implant outcome were assessed. Twenty-three sinus sites with 10 sinuses of the TG and 13 of the CG were ultimately available for data and statistical analysis. In the TG, a slightly, but yet significantly (p = .040) higher proportion of new bone formation (TG: 27.7 ± 5.6% vs. CG: 22.9 ± 5.1%) and a lesser (p = .019) amount of connective (non-mineralized) tissue (TG: 47.5 ± 9.5% vs. CG: 56.1 ± 9.5%) was found than in the CG. However, both xenografts showed comparable (n.s.) residual bone graft (TG: 23.7 ± 7.2% vs. CG: 21.1 ± 9.85.6%), bone-to-graft contacts (TG: 26.2 ± 9.8% vs. CG: 30.8 ± 13.8%), similar graft height reduction over time (TG: 12.9 ± 6.7% CG: 12.4 ± 5.8%) and implant survival/success rate (100%). At the 3-year post-loading evaluation, the peri-implant marginal bone loss (TG: 0.52 ± 0.19 mm; CG: 0.48 ± 0.15 mm) and the peri-implant health conditions (TG: 87.5%/CG: 81.2%) did not differ between implants inserted in both xenografts used. The use of DPBM or DBBM for maxillary sinus augmentation is associated with comparable bone formation providing stable graft dimension combined with healthy peri-implant conditions.

Clinical Outcomes of Descemet Membrane Endothelial Keratoplasty Using a Preloaded Imported Graft.

Although the popularity of Descemet membrane endothelial keratoplasty (DMEK) is increased, there is still few clinical studies in Korea. In this study, we aimed to report the initial clinical outcomes of DMEK in patients followed up for more than 6 months. A total of 96 eyes that underwent DMEK by a single surgeon for Fuchs endothelial corneal dystrophy, pseudophakic bullous keratopathy, or other indications were evaluated for best-corrected visual acuity (BCVA), endothelial cell density (ECD), central corneal thickness (CCT), postoperative complications, and graft survival. The postoperative BCVA significantly increased compared to the preoperative BCVA by 59.4% (1.00 ± 0.77 logarithm of the minimum angle of resolution vs. 0.67 ± 0.76 logarithm of the minimum angle of resolution, p &lt; 0.001). The average preoperative ECD was 754 ± 382 cells/mm2, increasing to 1,333 ± 562 cells/mm2 at 3 months (76.8%, p &lt; 0.001), 1,334 ± 632 cells/mm2 at 6 months (76.9%, p &lt; 0.001), 1,121 ± 474 cells/mm2 at 12 months (48.7%, p = 0.024), and 972 ± 458 cells/mm2 at 24 months postoperatively (28.9%, p = 0.445). Compared to 3 months, the ECD declined by 15.9% at 12 months (p = 0.009) and 27.1% at 24 months postoperatively (p = 0.158). The average CCT was 675 ± 113 μm preoperatively, decreasing to 581 ± 102, 574 ± 101, and 594 ± 94 μm at 6, 12, and 24 months after DMEK, respectively (p &lt; 0.001 between all follow-up time points). Allograft rejection was detected in three (3.1%) and 14 eyes (14.6%) underwent retransplantation at an average of 10.1 ± 8.4 months after DMEK. DMEK is promising for maintaining corneal clarity, low postoperative complication rates, and stable graft longevity.

Hybrid Regenerative Therapy for Successful Reconstruction of an Infected Traumatized Diabetic Foot Wound.

Diabetic foot ulcers are a significant complication of diabetes, affecting millions globally, and require appropriate antibiotics, surgical debridement, wound care, and metabolic optimization for management. This article presents an innovative hybrid regenerative therapy for reconstructing an infected, traumatized foot wound of a 62-year-old man with diabetes mellitus who presented with a week-old injury after a car accident. At presentation, he had a 14 × 10 cm dorsal foot wound with skin necrosis, pus discharge, and bony instability owing to partial fractures and joint dislocations. Antibiotics were administered to treat multidrug-resistant bacteria and followed by surgical debridement and the application of a portable Velnext negative pressure wound therapy device. Once the wound condition stabilized, hybrid regenerative therapy was performed weekly. Six milliliters platelet-rich plasma and 6 mL platelet-poor plasma were prepared from 27 mL of venous blood mixed with 3 mL sodium citrate and injected into the tendons, soft-tissues, and muscles. Next, the exposed bones and tendons were covered with platelet-rich fibrin and semi-occlusive membranes, and a Velnext negative pressure wound therapy device was applied over them. The wound improved progressively during the subsequent 6 weeks and was finally covered with a split-skin graft. The patient had a successful 18-month postoperative period until now with stable grafts, anatomical restoration, and excellent foot functionality. Thus, hybrid regenerative therapy, encompassing several prevalent methods for healing wounds, has excellent benefits for treating complex diabetic foot ulcers.

The Clinical Utility of Post-Transplant Monitoring of Donor-Specific Antibodies in Stable Renal Transplant Recipients: A Consensus Report With Guideline Statements for Clinical Practice.

Solid phase immunoassays improved the detection and determination of the antigen-specificity of donor-specific antibodies (DSA) to human leukocyte antigens (HLA). The widespread use of SPI in kidney transplantation also introduced new clinical dilemmas, such as whether patients should be monitored for DSA pre- or post-transplantation. Pretransplant screening through SPI has become standard practice and DSA are readily determined in case of suspected rejection. However, DSA monitoring in recipients with stable graft function has not been universally established as standard of care. This may be related to uncertainty regarding the clinical utility of DSA monitoring as a screening tool. This consensus report aims to appraise the clinical utility of DSA monitoring in recipients without overt signs of graft dysfunction, using the Wilson & Junger criteria for assessing the validity of a screening practice. To assess the evidence on DSA monitoring, the European Society for Organ Transplantation (ESOT) convened a dedicated workgroup, comprised of experts in transplantation nephrology and immunology, to review relevant literature. Guidelines and statements were developed during a consensus conference by Delphi methodology that took place in person in November 2022 in Prague. The findings and recommendations of the workgroup on subclinical DSA monitoring are presented in this article.

Local laboratory-run donor-derived cell-free DNA assay for rejection surveillance in heart transplantation-first six months of clinical experience.

Donor-derived cell-free DNA (dd-cfDNA) is a blood biomarker detecting graft injury with high negative predictive value. While non-invasive strategies for heart transplant (HTx) rejection surveillance are widely adopted in the United States with centralized testing, data on the feasibility of dd-cfDNA assay at the local level are lacking. Here, we report the first 6 months of experience with a local laboratory-run dd-cfDNA assay in the routine clinical surveillance setting. Twenty-six HTx patients with stable graft function were transitioned from endomyocardial biopsy-based (EMB) to dd-cfDNA-led rejection surveillance using a commercially available next-generation sequencing-based assay. In the 90 samples analyzed, dd-cfDNA fraction remained continuously low in most patients, thus 88% of surveillance EMBs could be safely avoided. In the case of ≥.25% dd-cfDNA, EMB was performed. There was no missed rejection. Our data show the feasibility to analyze dd-cfDNA at the local level and successful implementation of this non-invasive surveillance method into clinical practice, thus considerably reducing the frequency of invasive surveillance EMBs.

Surgical technique for explantation of a functioning cardiopulmonary complex in an experiment

Objective: to develop and approve the surgical technique for explantation of a functioning cardiopulmonary complex under normothermic autoperfusion.Materials and methods. Landrace pigs were used as the experimental model for a series of acute experiments (n = 10). During the experiment, invasive pressure in the cavities of the heart and main arteries, blood gas composition, and myocardial contractility were monitored. The functioning cardiopulmonary complex was explanted through a median sternotomy. The explanted complex was conditioned at 37–38 °C for 6 hours.Results. In the course of a series of experiments, it was shown that stable operation of the isolated heart-lung complex ex vivo for 6 hours was fundamentally possible provided that the parameters of the basic homeostasis constants are maintained. The technological solutions used made it possible to ensure safe hemodynamic and anatomical isolation of the working cardiopulmonary complex.Conclusion. The developed protocol for isolating a functioning cardiopulmonary complex allows to provide stable graft function for 6 hours under normothermic autoperfusion. Implementation of this concept in the development of transport systems would significantly facilitate their design and eliminate the use of expensive components. This would contribute to widespread introduction into clinical practice.

One donor cornea for three corneal transplants, including a novel surgical technique of combined tight suturing to reduce and crescentic lamellar grafting to strengthen Terrien’s marginal degeneration

We successfully utilized one donor cornea for three patients: firstly, a crescentic lamellar keratoplasty for Terrien’s marginal degeneration; secondly, Descemet’s membrane endothelial keratoplasty for Fuchs endothelial dystrophy; and finally, deep anterior lamellar keratoplasty for an advanced keratoconus patient. All three grafts were prepared during the first surgery, and the other two grafts were preserved and used on another day. Patients were followed up for 1 year, and all have good visual outcomes with stable grafts. Our first patient underwent a novel combined surgery of tight sutures for ectasia reduction that is usually performed at an earlier stage, with tissue augmentation using a lamellar graft meant for the later stage of the disease. With a successful outcome of up to 1-year follow-up, this technique can be considered in other suitable peripheral ectasias in the future. By sharing our experience, we hope that corneal surgeons and their patients at large will benefit.

Lower Circulating Cytotoxic T-Cell Frequency and Higher Intragraft Granzyme-B Expression Are Associated with Inflammatory Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Recipients.

Background and Objectives: Inflammatory interstitial fibrosis and tubular atrophy (i-IFTA) is an inflammation in the area of tubular atrophy and fibrosis. i-IFTA is poorly associated with graft outcome and associated with infiltration of inflammatory mononuclear cells. A cytotoxic T cell is a granzyme B+CD8+CD3+ T cell, mainly secret granzyme B. Granzyme B is a serine protease that may mediate allograft injury and inflammatory interstitial fibrosis and tubular atrophy (i-IFTA). However, there is no report identifying the association of granzyme B with i-IFTA after a long post-transplant interval. Material and Methods: In this study, we have measured the cytotoxic T-cell frequency with flow cytometry, serum and PBMCs culture supernatants granzyme-B levels with ELISA and intragraft granzyme-B mRNA transcript expression with the RT-PCR in RTRs in 30 patients with biopsy-proven i-IFTA and 10 patients with stable graft function. Result: The frequency of cytotoxic T cells (CD3+CD8+ granzyme B+) in SGF vs. i-IFTA was (27.96 ± 4.86 vs. 23.19 ± 3.85%, p = 0.011), the serum granzyme-B level was (100.82 ± 22.41 vs. 130.32 ± 46.60, p = 0.038 pg/mL) and the intragraft granzyme-B mRNA transcript expression was (1.01 ± 0.048 vs. 2.10 ± 1.02, p < 0.001 fold). The frequency of CD3+ T cells in SGF vs. i-IFTA was (66.08 ± 6.8 vs. 65.18 ± 9.35%; p = 0.68) and that of CD3+CD8+ T cells was (37.29 ± 4.11 vs. 34.68 ± 5.43%; p = 0.28), which were similar between the 2 groups. CTLc frequency was negatively correlated with urine proteinuria (r = -0.51, p < 0.001), serum creatinine (r = -0.28, p = 0.007) and eGFR (r = -0.28, p = 0.037). Similarly, the PBMC culture supernatants granzyme-B level was negatively correlated with urine proteinuria (r = -0.37, p < 0.001) and serum creatinine (r = -0.31, p = 0.002), while the serum granzyme-B level (r = 0.343, p = 0.001) and intragraft granzyme-B mRNA transcript expression (r = 0.38, p < 0.001) were positively correlated with proteinuria. Conclusions: A decrease in the CTLc frequency in circulation and an increased serum granzyme-B level and intragraft granzyme-B mRNA expression shows that cytotoxic T cells may mediate the allograft injury in RTRs with i-IFTA by releasing granzyme B in serum and intragraft tissue.

#3003 IMPACT OF FULL CORRECTION OF HEMOGLOBIN AMONG POST-TRANSPLANT ANEMIC KIDNEY TRANSPLANT RECIPIENTS: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL

Abstract Background and Aims Several studies have shown that post-transplant anemia (PTA) might be associated with increased mortality and decreased graft survival and de-novo congestive heart failure. So we aimed from this prospective randomized controlled study to assess the impact of full correction of PTA on the cardiovascular system of renal transplant recipients receiving erythropoietin stimulating agents (ESA). Method We recruited 247 kidney recipients with stable graft function in this RCT with 2 groups according to their target hemoglobin (11-12 g/dl, group 1, n=183) and (13:15 g/dl, group 2, n=64). After correction of deficiencies, the target hemoglobin was achieved using ESA. All patients were followed up clinically and Laboratory and radiologically for 12 months. Results Diabetic nephropathy was the main cause of ESKD in group 1. The studied groups were comparable regarding pre-transplant co-morbidities. Most patients received thymoglobulin as induction then cyclosporine based maintenance immunosuppression. We did not find any significant difference between the two groups concerning post-transplant diabetes, BK viremia or malignancies and even cardiovascular events (TIA, stroke, ACS), (p&amp;gt;0.05). Group 1 showed higher mean blood pressure (P = .003), lower LV internal dimensions, higher LVH, LV mass, IVSD and LV mass index after one year of the study (p&amp;lt; 0.05). MIVSD, mean ejection fraction and FS were comparable in both groups (p&amp;gt;0.05). Graft outcome was comparable between both groups (P = .125), meanwhile mortality cases were significantly higher among group 1 (16 cases, 8.7%) (P = .005). Conclusion Full correction of PTA is associated with stabilized cardiac dimensions indices without any significant cardiovascular comorbidities.

#4699 QUALITY OF LIFE AS REPRESENTED BY PHYSICAL ACTIVITY WAS IMPROVING AFTER FULL CORRECTION OF POST-TRANSPLANT ANEMIA

Abstract Background and Aims Recent studies showed positive impact of correction of post-transplant anemia (PTA) on general health, exercise capacity, and physical scores. So we conducted this prospective randomized controlled trial (RCT) to assess quality of life after full correction of post-transplant anemia in renal recipients receiving erythropoietin stimulating agents. Method We recruited 247 kidney transplant recipients with stable graft function in this RCT with 2 groups according to their target hemoglobin (11-12 g/dl, group 1, n = 183) and (13:15 g/dl (group 2, n = 64) which was achieved using erythropoietin stimulating agents (ESA). Monthly clinical and laboratory evaluation of kidney graft function was carried out. Quality of life (QOL) was assessed –using 25 and 36 questionnaires-at the start and 12 months. Results We observed more females in group 1 and the original kidney disease was chronic glomerulonephritis was significantly higher in group 2 (37.5%) followed by diabetic nephropathy (15.7%) while in group 1 it came as 25.7% and 22.4% respectively (p&amp;lt;0.05).The studied groups were comparable regarding pre-transplant co-morbidities. Most patients received thymoglobulin as induction and most of them were maintained on cyclosporine. We did not find any significant difference between the two groups concerning post-transplant co-morbidities (p &amp;gt;0.05), however better graft function was observed in group 2 at 6 months (p&amp;lt; 0.05). At 12 months, the assessment of QoL using the Medical Outcomes Study 36-Item Short-Form Health Survey, group 1 showed better post-transplant physical features and higher emotional factors related inactivity at 12 month (p&amp;lt;0.05), while group 2 showed significantly higher basal and 12 months activity state (p = 0.05). Basal inactivity was comparable in group 2 with that at 12 months (p&amp;gt;0.05), emotional factors related inactivity was significantly higher at 12 months in group 1. Graft outcome was comparable between both groups (p = 0.125), (p = 0.005). Conclusion Quality of life as represented by physical activity was improving by full correction of PTA in renal transplant recipients receiving ESA.

Introducing Saddle-Shaped Radix Graft, with a Second Look into the Classic.

An enduringly stable tip graft is the key to achieve successful rhinoplasty cases. However, the intrinsic nature of rib graft warping renders major unpredictability for the long-term outcome. The objective of this study was to detail and validate the use of a radix graft design that is characterized by the dual curved surfaces and beveled margin, which consequently renders a shape similar to a saddle. Twenty-three female patients, ranging in age from 22 to 31 years, completed the study. In all cases, the saddle-shaped radix graft was applied as the essential element for enhancing radix region profile. The complications that arose were collected retrospectively. Three-dimensional stereophotogrammetric evaluations of patients were performed. Anthropometric points were analyzed in a blinded fashion. Outcome variables were tip projection, nasal length, radix height, and the radius of curvature. Postoperative analysis suggested significant improvement on the aesthetics of the radix region over time, evidenced by the significant increase of radix height (4.33 ± 1.21 mm versus 7.08 ± 1.00 mm), and the reduction of radius of curvature at nasofrontal break over the long term (22.63 ± 2.24 mm versus 13.94 ± 0.98 mm). Other postoperative evaluations, including radix height, tip projection, and nasal length, had significant improvement. The saddle-shaped radix graft effectively augments the radix area and creates an aesthetically pleasant nasofrontal break without causing the elevated radix deformity. It has the merits of anatomical compliance and flexibility when it comes to concomitantly improving the glabella-radix profile for those East Asians with extremely low radix.