Common Cause Of Graft Failure Research Articles

Novel factors potentially initiating acute antibody-mediated rejection in pig kidney xenografts despite an efficient immunosuppressive regimen.

Antibody-mediated rejection (AMR) is a common cause of graft failure after pig-to-nonhuman primate organ transplantation, even when the graft is from a pig with multiple genetic modifications. The specific factors that initiate AMR are often uncertain. We report two cases of pig kidney transplantation into immunosuppressed baboons in which we identify novel factors associated with the initiation of AMR. In the first, membranous nephropathy was the initiating factor that was then associated with the apparent loss of the therapeutic anti-CD154 monoclonal antibody in the urine when severe proteinuria was present. This observation suggests that proteinuria may be associated with the loss of any therapeutic monoclonal antibody, for example, anti-CD154 or eculizumab, in the urine, resulting in xenograft rejection. In the second case, the sequence of events and histopathology tentatively suggested that pyelonephritis may have initiated acute-onset AMR. The association of a urinary infection with graft rejection has been well-documented in ABO-incompatible kidney allotransplantation based on the expression of an antigen on the invading microorganism shared with the kidney graft, generating an immune response to the graft. To our knowledge, these potential initiating factors of AMR in pig xenografts have not been highlighted previously.

Indications and Outcomes of Repeat Keratoplasty for Graft Failure at a Tertiary Eye Care Center in Nepal.

Graft failure is a common complication following keratoplasty requiring repeat keratoplasty (re-KP). To determine the indications and outcome of repeat keratoplasty at a tertiary eye care centre in Nepal. This was a retrospective study of 78 patients who underwent re-KP for graft failure in Tilganga Institute of Ophthalmology from Jan 2015 to Dec 2020. Indications for the primary keratoplasty, causes of graft failure and outcomes of re-KP in terms of vision acuity, graft clarity and secondary glaucoma were evaluated. Cases of regraft with less than one-year follow-up period were excluded. A total of 78 re-KPs had been performed in 78 patients during the study period. Seventy eyes had undergone single corneal regraft and 8 eyes had undergone multiple (second or third) regraft surgery. Most common indication of primary keratoplasty was infectious keratitis (n=36; 46.2%). On follow up, 36 eyes (46.2%) were clear at the last visit, of which 31 eyes were single regraft cases and 5 were of multiple regraft cases. Most common cause of graft failure was graft infection (n=34; 43.6%) followed by corneal scarring (n=12; 15.4%). Of 42 eyes with failed regrafts, recurrence of the preoperative infection was commonest cause (n=15, 35.7%) followed by secondary glaucoma (n=11; 26.2%). Of 36 eyes with clear regraft, only 4 eyes (11.11%) achieved best corrected vision of ≥6/18 and remaining 32 eyes had BCVA <6/18 due to associated cataract, secondary glaucoma and high astigmatism. The most common cause for re-KP includes graft infection followed by secondary glaucoma. Outcomes of corneal regrafts in the form of graft clarity and visual acuity are suboptimal.

Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small-diameter vascular grafts by modulating the local inflammatory response.

Small-diameter vascular grafts (diameter <6mm) are in high demand in clinical practice. Neointimal hyperplasia, a common complication after implantation of small-diameter vascular grafts, is one of the common causes of graft failure. Modulation of local inflammatory responses is a promising strategy to attenuates neointimal hyperplasia. Vascular endothelial growth factor (VEGF) is an angiogenesis stimulator that also induces macrophage polarization and modulates inflammatory responses. In the present study, we evaluated the effect of VEGF on the neointima hyperplasia and local inflammatory responses of decellularized vascular grafts. In the presence of rhVEGF-165 in RAW264.6 macrophage culture, rhVEGF-165 induces RAW264.6 macrophage polarization to M2 phenotype. Decellularized bovine internal mammary arteries were implanted into the subcutaneous and infrarenal abdominal aorta of New Zealand rabbits, with rhVEGF-165 applied locally to the adventitial of the grafts. The vascular grafts were removed en-bloc and submitted to histological and immunofluorescence analyses on days 7 and 28 following implantation. The thickness of the fibrous capsule and neointima was thinner in the VEGF group than that in the control group. In the immunofluorescence analysis, the number of M2 macrophages and the ratio of M2/M1 macrophages in vascular grafts in the VEGF group were higher than those in the control group, and the proinflammatory factor IL-1 was expressed less than in the control group, but the anti-inflammatory factor IL-10 was expressed more. In conclusion, local VEGF administration attenuates neointimal hyperplasia in decellularized small-diameter vascular grafts by inducing macrophage M2 polarization and modulating the inflammatory response.

Surgical outcomes of concomitantly performed penetrating keratoplasty with intrascleral haptic fixation.

Purpose:To describe the surgical results of concomitantly performed optical penetrating keratoplasty (PKP) with glued intrascleral haptic fixation (ISHF).Methods:Retrospective review of 18 patients (15–72 years) with best-corrected visual acuity (BCVA) of ≤1/60 subjected to unilateral concomitant optical PKP with ISHF and followed up for 13.11 ± 5.83 months (6–26 months) was undertaken.Results:The most common diagnoses were failed PKP (9/18, 50%) followed by aphakic bullous keratopathy (5/18, 27%). Preoperative glaucoma, peripheral anterior synechiae (PAS), and deep vascularization were present in 7/18 (38.88%), 12/18 (61.11%), and 5/18 (27.77%) patients, respectively. Intraoperatively, concomitant procedures such as pupilloplasty and intraocular lens explant were undertaken in 5/18 (27.277%) patients and 1/18 patients (5.55%) experienced suprachoroidal hemorrhage. At final follow-up, BCVA was ≥6/60 in 50% patients (mean astigmatism: 4.79 ± 1.68D), and 55.55% cases experienced graft failure (90% failed within one year of surgery). The most common causes of graft failure were glaucoma (50%), glaucoma with rejection (20%), rejection (10%), retinal detachment (10%), and suprachoroidal hemorrhage (10%). The ODDS ratio (OR) of having graft failure with the following factors was postoperative secondary interventions (OR: 6), postoperative complications (OR: 2.25), prior failed graft (OR: 1.8), preoperative PAS (OR: 1.75), intraoperative concomitant procedures (OR: 1.5), preoperative glaucoma (OR: 1.33), previous surgeries (OR: 1.24), and deep corneal vessels (OR: 0.66).Conclusion:All patients underlying PKP combined with glued ISHF must be counseled about suboptimal surgical outcomes. Emphasis is laid on appropriate case selection and stringent follow-up during the first year after surgery. Secondary interventions should be undertaken cautiously and judiciously in these patients.

Predictors of Graft Outcome in Renal Transplant Recipients with Antibody-Mediated Rejection

Active and chronic antibody-mediated rejection (AMR) is a common cause of graft failure. Prognostic markers of this complication are not well defined. We aimed to find out the demographic, histopathological and clinical characteristics of transplant recipients who developed AMR and to evaluate the impact of these features as well as antirejection treatment modalities on graft survival.

Shear wave elastography in transplant kidney and its correlation with renal doppler parameters and eGFR

Chronic allograft nephropathy is the most common cause of graft failure and is characterized by interstitial fibrosis and tubular atrophy, this study evaluated the role of shear-wave sonoelastography in the differentiation of stable renal allograft from allograft dysfunction & establish the correlation of parenchymal stiffness values with resistive index (RI), serum creatinine level, estimated glomerular filtration rate (eGFR). A prospective study of 40 patients who had undergone renal transplantation was conducted between October 2018 and July 2020. Patients were classified as having stable allograft and allograft dysfunction on the basis of clinical parameters practised in our institution. Receiver operating characteristic curve were drawn to obtain a cut off value with maximum sensitivity and specificity. Pearson’s correlation was used to evaluate different renal parameters and their correlation with the shear wave elastography (SWE) value. In this study 27 patients had graft dysfunction and 13 had stable graft. Use of the threshold value of 8.23kPa for SWE resulted in a sensitivity of 70% and specificity of 100% for the differentiation of stable allograft from allograft dysfunction. Parenchymal stiffness showed inverse correlation with eGFR (r = -.756, P

Predictors of graft outcome in renal transplant recipients with antibody-mediated rejection

Abstract. Active and chronic antibody-mediated rejection (ABMR) is a common cause of graft failure. Prognostic markers of this complication are not well defined. We aimed to find out the demographic, histopathological and clinical characteristics of transplant recipients who developed ABMR and evaluate the impact of these features, and anti-rejection treatment modalities on graft survival. &#x0D; Methods. Thirty-two patients who developed ABMR (22 male; mean age 40.59±12.52 years) were included in this study. Data were evaluated retrospectively and graft survival was analyzed. All transplant biopsies were evaluated according to Banff's 2013 classification.&#x0D; Results. Among the 32 cases, 26 were transplanted from living donors. Mean serum creatinine at the time of biopsy was 1.99 ±0.09 mg/dL. Proteinuria was 1566.06±353.92 mg/day at the time of biopsy. The need for hemodialysis was significantly related with initial creatinine (p = 0.003); creatinine after three months (p &lt; 0.001) and final creatinine (p &lt; 0.001) as well as initial proteinuria (p = 0.005); proteinuria after three months (p &lt; 0.001) and final proteinuria (p &lt; 0.001). 6 cases showed diffuse C4d positivity, 26 cases showed focal c4d positivity. Five of 6 patients with diffuse C4d staining in renal biopsy were hemodialyzed at first and third months despite anti-rejection therapy (p=0.029 and 0.041, respectively).&#x0D; Mean survival time was 1654.67±220.40 (95% CI 1222.68-2086.66) days for focal staining C4d cases and 366.16±36.44 (95% CI 294.73-437.60) days for diffuse staining C4d cases. The difference was statistically significant (p=0.012). Two of the patients died, 15 experienced graft loss and 17 survived with functioning grafts. Mean survival time between anti-rejection treatment modalities showed no statistical significance (p=0.15)&#x0D; Conclusions. Serum creatinine, proteinuria at the time of biopsy, diffuse peritubular C4d staining were significantly associated with graft survival. Early diagnosis is important to improve success in the treatment of ABMR and graft survival

Dropless penetrating keratoplasty: immunosuppression by a subconjunctival dexamethasone implant, pilot tolerance and safety study

AbstractPurposePenetrating keratoplasty (PK) remains the first technic of corneal transplantation worldwide and rejection a common cause of graft failure. Its prevention has been based for decades on repeated instillation of steroid eye drops (dexamethasone, prednisolone, rimexolone). Nevertheless, the overall survival of corneal transplants, all indications combined, is lower than that of some organ transplants. Both compliance and the discontinuous nature of the eye drops may be involved. The improvement of immunosuppression could avoid numerous graft failures. In a rabbit model of PK, we previously demonstrated that a subconjunctival dexamethasone implant (Ozurdex) was well tolerated and prevented rejection as efficiently as steroid eye drops trice daily during the first 5‐6 weeks. We then designed a clinical trial to first investigate the tolerance and safety of subconjunctival Ozurdex after PK.MethodsSingle centre, phase II non‐randomized tolerance and safety pilot study on 14 patients (NCT02834260). Designed to analyze the risk of increased intraocular pressure (IOP, primary endpoint at month 1), possible discomfort, resorption time, and collect initial efficacy data. The implant was injected at the 12 o'clock position, 5 mm from the limbus, at the end of PK, in order to deliver dexamethasone immediately. A steroid eye drop relay was planned at the time of complete resorption of the implant. Patients were monitored at regular intervals during 12 months: IOP, discomfort and redness scores, implant status, rejection episode, endothelial cell density, and central corneal thickness by OCT. An independent adverse event committee gave its opinion after the first patient, then at regular intervals.ResultsNo increase in IOP, no adverse event related to the implant was observed. The average duration of resorption was 6 weeks. The therapeutic relay with dexamethasone eye drops was uneventful.ConclusionsHis is the first proof of concept that dropless immunosuppression is possible after penetrating keratoplasty. Ozurdex, chosen here because it was the only ophthalmological steroid implant marketed in France, obviously resorbs too quickly, but this work paves the way for the use of other implants that release a steroid or another immunosuppressive agent in the very long term.

Recurrent Glomerulonephritis after Renal Transplantation: The Clinical Problem.

Glomerulonephritis (GN) continues to be one of the main causes of end-stage kidney disease (ESKD) with an incidence rating from 10.5% to 38.2%. Therefore, recurrent GN, previously considered to be a minor contributor to graft loss, is the third most common cause of graft failure 10 years after renal transplantation. However, the incidence, pathogenesis, and natural course of recurrences are still not completely understood. This review focuses on the most frequent diseases that recur after renal transplantation, analyzing rate of recurrence, epidemiology and risk factors, pathogenesis and bimolecular mechanisms, clinical presentation, diagnosis, and therapy, taking into consideration the limited data available in the literature. First of all, the risk for recurrence depends on the type of glomerulonephritis. For example, recipient patients with anti-glomerular basement membrane (GBM) disease present recurrence rarely, but often exhibit rapid graft loss. On the other hand, recipient patients with C3 glomerulonephritis present recurrence in more than 50% of cases, although the disease is generally slowly progressive. It should not be forgotten that every condition that can lead to chronic graft dysfunction should be considered in the differential diagnosis of recurrence. Therefore, a complete workup of renal biopsy, including light, immunofluorescence and electron microscopy study, is essential to provide the diagnosis, excluding alternative diagnosis that may require different treatment. We will examine in detail the biomolecular mechanisms of both native and transplanted kidney diseases, monitoring the risk of recurrence and optimizing the available treatment options.

Therapeutic Apheresis in Glomerular Diseases after Kidney Transplantation

Therapeutic apheresis is an extracorporeal treatment that selectively separates abnormal cells or substances from the blood that are linked with or cause certain disease states. It is widely used in transplantation medicine as an adjunctive therapeutic option.In kidney transplantation (KT), recurrent and de novo glomerular diseases represent the third most common cause of graft failure beyond the first year after transplantation, as current therapeutic options are limited. Evidence to support the use of therapeutic apheresis in these conditions is scarce, as it is only supported by observational studies. The purpose of this review was to examine and clarify the potential role of therapeutic apheresis and describe current evidence in the treatment of recurrent and de novo glomerular diseases after KT.

Analysis of Graft Failure After Primary Penetrating Keratoplasty in Children With Peters Anomaly.

To investigate the causes of graft failure and risk factors associated with total graft opacity after primary penetrating keratoplasty (PK) in children with Peters anomaly (PA). In this retrospective study, patients with PA (younger than 5 years) who received primary PK in Beijing Tongren Hospital were reviewed. The follow-up period was a minimum of 6 months. A modified PA classification system was used, and all failed grafts were categorized into partial and total opacity groups. Patient demographics, PA classification, operation details, degree of graft opacity, and causes of graft failure were recorded. Of the 165 eyes, 54 eyes (32.7%) demonstrated graft failure along with various degrees of graft opacity. Approximately half of the grafts applied failed within 6 months postoperatively. The partial and total opacity groups did not demonstrate any significant differences regarding diagnosis distribution. Irreversible immune rejection accounted for 61.1% of all graft failures; furthermore, it had a significantly higher proportion in the partial opacity group than in the total opacity group (71.0% and 47.8%, respectively; P = 0.058). The degree of graft opacity was significantly associated with patient age at surgery (P = 0.002), preoperative corneal vascularization (P = 0.009), and iris defects (P = 0.001). However, administration of intensive topical corticosteroids could reduce the risk of total opacity in the rejected grafts. Irreversible immune rejection is the most common cause of graft failure after primary PK in pediatric patients with PA. The degree of graft opacity is closely related to patient age at surgery, preoperative corneal vascularization, and iris defects.

Histopathological characteristics and causes of kidney graft failure in the current era of immunosuppression.

BACKGROUNDThe histopathological findings on the failing kidney allograft in the modern era is not well studied. In this study, we present our experience working with kidney transplant recipients with graft failure within one year of the biopsy.AIMTo report the histopathological characteristics of failed kidney allografts in the current era of immunosuppression based on the time after transplant, cause of the end-stage renal disease and induction immunosuppressive medications.METHODSIn a single-center observational study, we characterized the histopathological findings of allograft biopsies in kidney transplant recipients with graft failure within one year after the biopsy.RESULTSWe identified 329 patients with graft failure that met the selection criteria between January 1, 2006 and December 31, 2016. The three most common biopsy findings were interstitial fibrosis and tubular atrophy (IFTA, 53%), acute rejection (AR, 43%) and transplant glomerulopathy (TG, 33%). Similarly, the three most common causes of graft failure based on the primary diagnosis were AR (40%), TG (17%), and IFTA (13%). Most grafts failed within two years of post-transplant (36%). Subsequently, approximately 10%-15% of grafts failed every two years: > 2-4 years (16%), > 4-6 years (13%), > 6-8 years (11%), > 8-10 years (9%) and > 10 years (16%). AR was the most common cause of graft failure in the first six years (48%), whereas TG was the most prevalent cause of graft failure after 6 years (32%) of transplant.CONCLUSIONIn the current era of immunosuppression, AR is still the most common cause of early graft failure, while TG is the most prevalent cause of late graft failure.

What are the Histopathologic Findings in Pulmonary Allografts with Graft Failure?

Purpose The goal of this study was to investigate the pathology of graft failure in a series of explants and autopsies with special emphasis on chronic lung allograft dysfunction (CLAD). Methods Histopathologic evaluation was performed on a series of pulmonary allografts, received either at the time of re-transplantation or at autopsy, from patients with primary lung allograft failure, over a 13-year period. The findings were categorized as acute and organizing alveolar injury, obliterative bronchiolitis (OB), restrictive CLAD (including acute fibrinoid organizing pneumonia [AFOP]/interstitial-pleuroparenchymal fibrosis), mixed obliterative and restrictive, and other. Results Twenty-two lungs were examined retrospectively. Of these, 19 (86%) were explants and 3 (14%) were from autopsies. Fourteen patients were male (64%) and 8 were female (36%). For men, the average age was 58 ± 4 years at transplant, while the average age for females was 48 ± 5 at transplant. The median duration of transplant was 468 days. Eight cases showed acute and organizing alveolar injury (36%, mean 300 days post-transplant), 4 showed pure OB (18%, mean 1400 days post-transplant), zero showed pure restrictive CLAD, 6 showed mixed obliterative and restrictive disease (27%, mean 1076 days post-transplant), and 4 were categorized as other (18%, mean 375 days post-transplant). The latter 4 allografts showed aspiration, HPE, bronchiectasis, and acute cellular rejection. Of the restrictive CLAD allografts, 5 showed AFOP with interstitial fibrosis, while 1 was primarily pleuroparenchymal fibroelastosis. One of 4 allografts with OB and 4 of 6 allografts with mixed CLAD + OB had focal acute and organizing alveolar injury. Vasculitis was present in 3 of 6 allografts with mixed CLAD + OB and 1 of 4 allografts with pure OB. Irregular scars with plasma cell infiltrates seen in 2 of 6 allografts with mixed CLAD + OB and in 1 of 4 allografts with pure OB. Conclusion CLAD and acute alveolar injury are the most common causes of graft failure. Alveolar injury is usually soon after transplant but may also occur late. Restrictive CLAD was not seen in the absence of OB in this study. The median graft survival was similar in the pure OB and mixed CLAD groups.

Retransplantation after Living Donor Liver Transplantation

Introduction Living donor liver transplant (LDLT) is associated with a higher incidence of post-transplant vascular and biliary complications, however it is also known that graft and patient survival after LDLT is similar to graft and patient survival following deceased donor liver transplantation (DDLT). Outcomes for retransplantation (reLT) after LDLT are not well understood; this study aimed to review the need for reLT following LDLT using data from the Adult to Adult Living Donor Liver Transplantation Study (A2ALL). Materials and Methods Demographics and outcomes of donors and recipients in the A2ALL cohort who underwent LDLT between April 1998 and January 2014 were reviewed. We compared recipients who underwent LDLT followed by reLT to recipients that underwent LDLT alone. Descriptive analysis was performed using Wilcoxon rank sum and chi-squared tests; patient survival was estimated using Kaplan-Meier methods and compared by the log-rank test. Results 1065 donor/recipient pairs were included in the analysis. 110 recipients (10.3%) required reLT following initial LDLT. reLT patients were predominantly male (65.5%) and Caucasian (94.5%), with a median (IQR) age of 49.2 years (40.9-57.3), median BMI of 25 (23-28), and median MELD of 16 (12-20). The majority were right lobe recipients (93.6%) and related to their donor (59.1%). Compared with patients who underwent LDLT alone, reLT patients were slightly younger (49.2 vs. 52.8 years, p=0.001) and had a higher total bilirubin at the time of LDLT (3.1 vs. 2.6, p=0.02). The most common cause of graft failure was vascular thrombosis (47.8%) followed by primary graft failure (19.4%), other (13.4%), and recurrent hepatitis (10.4%). ReLT patients had a longer length of stay in the hospital (18 vs. 10, p<0.001) and ICU (3 vs. 1 days, p<0.001) after initial LDLT, and a greater number of complications (5 vs. 3, p<0.001). Patient survival after initial LDLT was significantly lower for reLT versus LDLT alone (p<0.001). Survival (95% CI) for reLT and LDLT patients, respectively, was 86.2% (78-92) vs. 91.6% (90-93) at 1-year, 63.5% (53-73) vs. 81.9% (79-85) at 5-years, and 44.1% (31-56) vs. 67.9% (64-72) at 10-years (Figure 1). Discussion In this cohort, vascular thrombosis and primary graft failure accounted for more than two thirds of all reLT after LDLT. In the United States, patients with these diagnoses may be listed as Status 1 and move to the top of the waitlist for deceased donor organs. However, reLT is associated with significant mortality and patients who require reLT following LDLT have significantly worse long-term survival post-transplant. ReLT poses a complex ethical and emotional dilemma for the transplant team, particularly in the case of reLT following LDLT. Conclusion Vascular thrombosis and primary graft failure are the most common indications for reLT following LDLT. ReLT after LDLT is associated with significantly worse patient survival at 5 and 10 years post-transplant.

CD9+ Regulatory B Lymphocytes Control Chronic Lung Inflammation by Inducing Effector T Cell Apoptosis

The occurrence of chronic lung allograft dysfunction (CLAD) is the main complication after lung transplantation (LT) and remains the most common cause of graft failure and death. Currently, the available immunosuppressive therapies cannot prevent its occurrence in 50% of patients at 5 years. Conversely, some LT recipients, remain free of CLAD for a long time, and are considered as stable (STA). Whereas in kidney transplantation, predictive B-cell signature of long term or poor graft outcome have been identified by us and others, nothing has been done yet in lung transplantation. We aim to identify and validate predictive B lymphocyte signatures in order to identify and lighten the risk of CLAD and allow for early intervention before irreversible damages. PBMCs from the Lung Transplanted patients (COLT) COhort were immunophenotyped before LT, and at regular time points after LT. PBMCs from 21 patients with bronchiolitis obliterans syndrome and 21 patients with long-term functional stability (STA) were analyzed. 20 healthy volunteers (HV) were analyzed as controls. Cells were stained for the B-cell markers CD19, CD27, CD38, CD138, CD22, CD24, IgD, IgM, CD5 and CD9 to determine the percentage of transitional, naive, plasmablast, memory and regulatory B-cells. No differences were observed between the groups for CD19+ B cells, naive, memory and plasma B cells. However, both the level of CD38hiCD24hi transitional and CD9+ B cells secreting IL-10 were highly associated with bronchiolitis obliterans syndrome–free survival at 24 months after lung transplantation before the appearance of symptoms. Patients with CD9+ or transitional B cell frequency below 5.4% and 2.24%, respectively (sensitivity = 100%), displayed significantly higher incidence of bronchiolitis obliterans syndrome. In summary, these data associate IL-10-secreting CD24hiCD38hi transitional and CD9+ B cells with better allograft outcome in LT patients. B cell subsets and possibly their production of IL-10 may contribute to create a favorable environment that might be essential for the maintenance of long-term stable graft function. The identification of CD9-expressing B cells as a new predictive biomarker of bronchiolitis obliterans syndrome–free survival provide new strategies for prediction and treatment of the pathology.

Lateral Intercondylar Ridge: Is it a reliable landmark for femoral ACL insertion?: An anatomical study

BackgroundIncorrect femoral tunnel placement is the most common cause of graft failure during Anterior Cruciate Ligament (ACL) Reconstruction. A reliable landmark can minimize errors. AimTo identify whether the Lateral Intercondylar Ridge (LIR) is a consistent anatomical structure and define its relationship with the femoral ACL insertion. Materials and methodsPhase 1: we studied 23 femoral dry bone specimens macroscopically. Using a digital microscribe, the medial surface of the lateral femoral condyle was reconstructed (3D) to evaluate whether there was an identifiable bony ridge.Phase 2: 7 cadaveric specimens with intact soft tissues were dissected to identify the femoral ACL insertion. A 3D reconstruction of the femoral ACL insertion and the surface allowed us to define the relationship between the LIR and the ACL insertion. ResultsAll specimens had a defined LIR on the medial surface of the lateral femoral condyle. The ridge was consistently located just anterior to the femoral ACL insertion. The ACL footprint was present in the depression between the ridge and the Inferior Articular Cartilage Margin (IACM). The mean distance from the midpoint of the IACM to the LIR was 10.1 mm. ConclusionsThis is the first study to use the microscribe to digitally reconstruct the medial surface of the lateral femoral condyle. It shows that the LIR is a consistent anatomical structure that defines the anterior margin of the femoral ACL insertion, which guides femoral tunnel placement. Our findings support the ruler technique, which is a commonly used method for anatomic single bundle ACL reconstruction.

Revision Anterior Cruciate Ligament Reconstruction.

➤ Technical errors such as nonanatomic tunnel placement are some of the most common causes of graft failure after primary anterior cruciate ligament reconstruction (ACLR).➤ When considering a revision ACLR in a patient with ACL graft failure, it is crucial to perform preoperative imaging, which should include an initial radiographic series, magnetic resonance imaging, and possibly computed tomography for further assessment of tunnel locations.➤ Revision ACLR may be performed in a 1 or 2-stage procedure depending on the size and location of the existing tunnels, bone stock, existing hardware, and infection status.➤ Use of autograft ligament tissue for revision ACLR has been shown to correlate with higher patient-reported outcomes and a significantly lower risk of subsequent graft rupture in comparison with allograft use.➤ Multiple studies have shown that the rate of return to the preinjury level of sport is significantly lower following revision ACLR than following primary ACLR procedures.

Anatomy and Biomechanics of the Native and Reconstructed Anterior Cruciate Ligament: Surgical Implications.

➤ Technical errors, such as nonanatomic tunnel placement, are among the most common causes of graft failure after anterior cruciate ligament (ACL) reconstruction.➤ No clinical superiority has been demonstrated for double-bundle ACL reconstruction compared with single-bundle reconstruction.➤ Single-bundle reconstruction of the anteromedial bundle has been shown to restore kinematics to the level of the intact knee, whereas reconstruction of the posterolateral bundle results in high graft forces.➤ Regardless of surgical technique (single-bundle compared with double-bundle or anteromedial portal compared with transtibial), the surgeon should avoid placement of a vertical or low femoral tunnel, as this results in abnormal knee kinematics.➤ ACL reconstruction is a patient-specific procedure, whereby surgeons should attempt to restore the native anatomy of the knee on a case-by-case basis and must take into account specific risk factors for ACL graft failure, such as younger age, higher activity level, and use of allograft, when counseling patients.

The Diagnostic Impact of C4d, CD68, and NF-κB Expression in the Differentiation Between Recurrent Hepatitis C and Acute Cellular Rejection After Liver Transplantation.

Liver transplantation is the selected treatment for patients with advanced liver disease and cirrhosis, mostly as a complication of hepatitis C virus (HCV). Recurrent HCV and acute cellular rejection (ACR) of the graft are the most common causes of graft failure. The distinction between the 2 conditions is essential because they are managed differently. In some cases, the clinical and histopathologic features may overlap between recurrent hepatitis C and ACR, making differentiation difficult. The aim of this study was to investigate the role of C4d, CD68, and nuclear factor kappa-B (NF-κB) in the differentiation between ACR and recurrent HCV in the post-liver-transplant biopsy using immunohistochemistry. C4d expression in endothelial cells of portal or central veins (P=0.001) and the number of macrophages highlighted by CD68 (P=0.02) were in favor of ACR, whereas NF-κB expression by hepatocytes was in favor of recurrent hepatitis C. Vascular injury demonstrated by endothelial expression of C4d and prominent macrophage infiltration identified by CD68 expression were the distinguishing criteria for ACR and representing humoral and cellular-mediated immunity as evoking factors for graft injury. The upregulation of NF-κB in the hepatocytes of recurrent hepatitis C could be an immune response to infection or it may be induced by HCV itself.

Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1.

Chronic renal allograft dysfunction (CRAD) is the most common cause of graft failure following renal transplantation. However, the underlying mechanisms remain to be fully elucidated. Immunosuppressants and hyperlipidemia are associated with renal fibrosis following long-term use. The present study aimed to determine the effects of tacrolimus (FK506) and lipid metabolism disorder on CRAD. In vitro and in vivo models were used for this investigation. Cells of the mouse proximal renal tubular epithelial cell strain, NRK-52E, were cultured either with oxidized low-density lipoprotein (ox-LDL), FK506, ox-LDL combined with FK506, or vehicle, respectively. Changes in cell morphology and changes in the levels of lectin-like ox-LDL receptor-1 (LOX-1), reactive oxygen species (ROS), hydrogen peroxide and fibrosis-associated genes were evaluated at 24, 48 and 72 h. In separate experiment, total of 60 Sprague-Dawley rats were divided randomly into four groups, which included a high-fat group, FK506 group, high-fat combined with FK506 group, and control group. After 2, 4 and 8 weeks, the serum lipid levels, the levels of ox-LDL, ROS, and the expression levels of transforming growth factor (TGF)-β1 and connective tissue growth factor were determined. The in vitro and in vivo models revealed that lipid metabolism disorder and FK506 caused oxidative stress and a fibrogenic response. In addition, decreased levels of LOX-1 markedly reduced the levels of TGF-β1 in the in vitro model. Taken together, FK506 and dyslipidemia were found to be associated with CRAD following transplantation.