Risk Of Graft Failure Research Articles

Risk factors for corneal conjunctival grafting failure in dogs at four referral centers in the southern United States (203patients): 2015-2021.

To report risk factors associated with conjunctival graft failure in dogs at four referral specialty centers. Records of 203 dogs (229 eyes) undergoing conjunctival graft repair of ulcerative keratitis at four hospitals from 2015 to 2021 were reviewed. Success was defined as full graft integration with globe retention at the last postoperative evaluation; vision status was reported separately. Factors assessed included patient signalment, ophthalmic examination findings, surgical factors, and follow-up information. Conjunctival graft failure occurred in 11% (25/229) of eyes and was significantly associated with ulcer depth, with corneal perforations having increased odds of graft failure compared with descemetoceles (odds ratio [OR] = 3.22, 95% confidence interval [CI] 1.11-9.32; p = .03) and stromal ulcers (OR = 10.89 [95% CI 1.38-86.18], p = .02). Brachycephalic dogs were significantly more likely than non-brachycephalic dogs to experience graft failure (OR = 5.02 [95% CI 1.42-17.74], p < .01). Surgery on the opposite eye relative to surgeon handedness was significantly associated with an increased risk of graft failure (OR 4.28 [95% CI 1.53-11.94], p < .01). The use of 7-0 and 8-0 suture versus 9-0 (p = .03) and the use of a combined simple continuous and interrupted pattern (p = .03) were significantly associated with an increased risk of graft failure. At the last follow-up, (median 61.5 days), 87% of dogs were visual. Corneal perforations, surgery on the opposite eye relative to surgeon handedness, suture size and pattern, and brachycephalic conformation were significantly associated with an increased risk of graft failure in this study. These characteristics can be considered when determining prognosis for ulcerative keratitis requiring surgical intervention.

Fresh Osteochondral Allograft to Medial Femoral Condyle With Proximal Tibial Opening Wedge Osteotomy

Background: Contributors to knee degeneration include mechanical axis malalignment, patellar maltracking, meniscal deficiency, and tibiofemoral instability. Full-thickness osteochondral defects in young, active patients can lead to significant pain and instability. The gold standard treatment for large (&gt;2 cm2) osteochondral defects is an osteochondral allograft (OCA) which addresses the pathologic articular cartilage loss and underlying bone deficiency. While biologic failure of fresh OCAs is reported, the majority of early failures are attributed to unaddressed mechanical malalignment in the coronal plane. Proximal tibial osteotomy (PTO) corrects malalignment thereby unloading the affected medial compartment and the newly placed OCA, improving long-term survivability. Indications: OCAs are indicated for isolated osteochondral defects and lesions in active young patients. PTO is indicated for patients with varus malalignment who risk potential graft failure of the affected medial compartment. Technique Description: The articular cartilage defect is identified, and a guide pin is drilled in the center. The defect is templated and scored around the margins. A reamer is used to drill to a total depth of 7 to 8 mm. The recipient site is then dilated for graft insertion. On the donor graft, the harvest site is outlined and drilled to the proper diameter. Careful measurement is utilized to ensure graft depth measurements match the recipient site. Once sized, the graft is tapped into place obtaining an anatomic fit along its entire periphery. The osteotomy is performed by using guide pins to delineate the plane cutting the tibia. Fluoroscopy confirmed the osteotomy site and angle. A spacing plate was securely inserted with screws, with placement confirmed by fluoroscopy. Results: Fresh OCAs can restore osteochondral defects. PTO corrects malalignment and unloads the affected medial compartment, decreasing the risk of revision graft failure or total knee arthroplasty. Discussion: Clinical and biomechanical studies that compared isolated and concomitant procedures demonstrated that OCA with PTOs had significantly greater survival rates. Significant malalignment increases the risk of graft failure. It remains unclear whether concomitant osteotomy with osteoarticular allografts leads to increased complication risk; inherent risks remain associated with individual procedures. In adolescents, simultaneous corrective osteotomy along with fresh OCA may delay arthroplasty and associated ambulatory restrictions. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Biplanar Anterior Opening Wedge Proximal Tibial Osteotomy to Correct Reverse Tibial Slope

Background: Anatomically, native posterior tibial slope (PTS) ranges from 6° to 10° and have significant effects on cruciate ligament stability. PTS &lt;6° is correlated with increased posterior tibial translation (PTT) and force on the posterior cruciate ligament (PCL), predisposing individuals to PCL injuries and an increased risk of PCL graft attenuation. In rare cases, a reverse tibial slope can occur (&lt;0°) as a result of trauma, physeal arrest, or abnormal development. This results in increased PTT and can lead to posterior tibial subluxation. Reverse tibial slopes in patients can be treated with an anterior opening wedge proximal tibial osteotomy, which increases the PTS to a more anatomic position. Indications: Biplanar anterior opening wedge proximal tibial osteotomies are indicated in patients with a reverse tibial slope both with the absence of PCL insufficiency or in conjunction with PCL reconstruction. Technique Description: Under fluoroscopic imaging, 2 guide pins were placed perpendicular to the tibial shaft. An oscillating saw and osteotomes completed the osteotomy in line with the guide pins with the posterior cortex remaining intact. The osteotomy site was slowly opened with a spreader device to 9 mm until the posterior drawer was such that the palpable step-off between the anterior aspect of the medial femoral condyle and the medial tibial plateau was comparable to the contralateral knee. Due to the patient having slight valgus coronal plane alignment, an opening-wedge posteriorly sloped plate was then placed anterolaterally and fixed while wedges held the osteotomy open. Results: Biplanar anterior opening wedge osteotomies correct a flattened PTS and reverse tibial slope, and coronal malalignment, and has been shown to decrease PCL laxity, preventing future PCL failure. Discussion: Biomechanical studies have shown that decreased tibial slope is correlated with an increased risk of PCL injury and PCL graft failure. In patients with reverse tibial slope, experienced instability can mimic PCL insufficiency despite there being no ligamentous damage. We describe a technique that corrects reverse tibial slope and with a discussion of surgical pearls and pitfalls. This technique restores anatomic position and normal function of the knee while correcting the sagittal malalignment that could lead to future injuries. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Role of HLA in cardiothoracic transplantation.

In current clinical practice, transplant clinicians create collaborative working relationships with histocompatibility laboratory scientists to identify the risk of long-term graft failure, which may assist in establishing strategies for treatment and surveillance. Transplant immunology research also focuses on optimizing human leukocyte antibody tissue typing and defines the most effective test for detecting the presence of donor-specific antibodies. Although several studies have been conducted, data on pediatric heart transplant recipients are limited. Epitope load information may be utilized to identify donors with permissible human leukocyte antibody mismatches to increase transplant success. Although current guidelines do not consider human leukocyte antibody epitope-based matching tools, these guidelines could be useful for identifying recipients at a high risk of donor-specific antibody production, which would be appropriate for routine donor-specific antibody screening to initiate early interventions to prevent antibody-mediated rejection. Human leukocyte antibody matching at the epitope level offers an effective approach for identifying acceptable mismatches in sensitized patients and provides information about epitope loads. In the future, eplet matching may be used to define the best immunosuppressive therapy protocol for cardiothoracic organ transplantation. This report provides an overview of the role of human leukocyte antibodies in heart and lung transplantation.

Risk factors and outcomes of bloodstream infection from a urinary source in kidney transplant recipients.

Bacteriuria is common among kidney transplant recipients (KTR). Risk factors and outcomes associated with bloodstream infection due to a urinary source (BSIU) in KTR are poorly understood. This single center case-control study from 2010 to 2022 compared KTR with BSIU to those with bacteria without bloodstream infection (BU). Multivariable logistic regression identified BSIU risk factors, and Cox models assessed its impact on graft failure. Among 3435 patients, who underwent kidney transplantation at Emory Hospital, 757 (22%) developed bacteriuria, among whom 142 (18.8%) were BSIU. Male sex, presence of Escherichia coli, Klebsiella pneumoniae, or Pseudomonas species in urine culture, urethral stricture, neuromuscular bladder disorder, and history of diabetes-induced renal failure were independently associated with increased odds of BSIU (Male sex: aOR 2.29, 95% CI 1.52, 3.47, E. coli: aOR 5.14, 95% CI 3.02, 9.13; K. pneumoniae aOR 3.19, 95% CI 1.65, 6.27, Pseudomonas spp aOR 3.06, 95% CI 1.25, 7.18; urethral stricture: 4.10, 95% CI 1.63, 10.3, neuromuscular bladder disorder aOR 1.98, 95% CI 1.09, 3.53, diabetes: aOR 1.64, 95% CI 1.08, 2.49). BSIU was associated with increased hazard of graft failure (HR 1.52, 95% CI 1.05, 2.20). Close monitoring is warranted for male KTR with bacteriuria, those with urine cultures positive for Pseudomonas spp, K. pneumoniae, or E. coli, as well as KTR with a history of diabetes-induced renal failure, urethral stricture, or neuromuscular bladder disorder due to their risk for developing BSIU. Future research should explore strategies to mitigate BSIU risk in these high-risk KTR and reduce the associated risk of long-term graft failure.

The role of donor sex on the post-liver transplant outcomes in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) can result in hepatic decompensation and require liver transplantation (LT). This study investigates the effect of the sex of the donor and recipient as a prognostic risk factor for adverse outcomes after LT in patients with PSC. UNOS registry was used to select LT patients with PSC from 1987 to 2019. The study cohort was stratified based on the sex of the recipient and further subdivided based on the sex of the donor. The primary endpoints of this study were all-cause mortality and graft failure, which were evaluated using a sequential Cox regression analysis. This study included 2829 patients; 906 female recipients were transplanted from 441 male donors and 465 female donors. 1923 male recipients were transplanted from 1194 male donors and 729 female donors. Within the mismatch analyses, the male-to-male recipients also had a significantly reduced hazard ratio of graft failure compared to female-to-male transplants [aHR 0.51, 95% confidence interval (CI) 0.33-0.79, P = 0.003]. No difference in graft failure was observed in the mismatched female recipient subgroup. The mismatched male recipient group also showed a decreased hazard ratio of mortality from graft rejection and respiratory causes. No differences in specific mortality causes were identified in the mismatched female recipient group. This study demonstrated an increase in the risk of graft failure and mortality secondary to graft failure in male recipients of female donor livers. No differences in mortality or graft failure were identified in female recipients of male livers.

Extra-anatomic bypass procedures for severe aortoiliac occlusive disease-A cohort study.

Extra-anatomic bypass (ExAB) grafting has been questioned due its inferior durability compared to anatomic bypass for aortoiliac occlusive disease (AIOD). This study aims to present early and late outcomes of patients treated with ExAB as well as to evaluate potential prognostic factors. This is a retrospective cohort study presenting a series of patients treated with ExAB for AIOD. All patients were treated between 2005 and 2022 within the Vascular Surgery Unit of a University Surgery Clinic. Both early (30-day) and late outcomes were evaluated. Univariate and multivariate analyses were conducted for potential predictors. Kaplan-Meier curve was produced for long-term patency. A total of 41 patients were treated (85.3% males; mean age: 76.3 ± 4.2years). Indication for treatment included severe claudication or critical limb ischemia (Rutherford stages III-VI). The following procedures were recorded: Femorofemoral bypass (FFB; n = 21) and axillofemoral bypass (AxFB; n = 20). All procedures were conducted using synthetic grafts with external rings. Early outcomes included no death, no myocardial infarction, no major bleeding, no graft infection, and no major amputation. Regarding late outcomes, 14.6% patients were lost after the first month. For the rest of patients (n = 35), five-year primary patency was 88.6%, primary-assisted patency was 94.3%, and secondary patency was also 94.3%. Limb salvage was 100% within follow-up. Endarterectomy at the distal anastomosis was the only independent predictor associated with worse patency in the long-term (OR = 5.356; 95% CI (1.012-185.562); p = .041). FFB and AxFB is a safe and durable strategy for treating patients with severe AIOD where no other option is feasible. Regarding predictors, only endarterectomy at the distal anastomosis site was associated with an increased risk for graft failure.

Long-Term Outcomes after Conversion to a Belatacept-Based Immunosuppression in Kidney Transplant Recipients.

Conversion to a belatacept-based immunosuppression is currently used as a calcineurin inhibitor (CNI) avoidance strategy when the CNI-based standard-of-care immunosuppression is not tolerated after kidney transplantation. However, there is a lack of evidence on the long-term benefit and safety after conversion to belatacept. We prospectively enrolled 311 kidney transplant recipients from 2007 to 2020 from two referral centers, converted from CNI to belatacept after transplant according to a prespecified protocol. Patients were matched at the time of conversion to patients maintained with CNIs, using optimal matching. The primary end point was death-censored allograft survival at 7 years. The secondary end points were patient survival, eGFR, and safety outcomes, including serious viral infections, immune-related complications, antibody-mediated rejection, T-cell-mediated rejection, de novo anti-HLA donor-specific antibody, de novo diabetes, cardiovascular events, and oncologic complications. A total of 243 patients converted to belatacept (belatacept group) were matched to 243 patients maintained on CNIs (CNI control group). All recipient, transplant, functional, histologic, and immunologic parameters were well balanced between the two groups with a standardized mean difference below 0.05. At 7 years post-conversion to belatacept, allograft survival was 78% compared with 63% in the CNI control group ( P < 0.001 for log-rank test). The safety outcomes showed a similar rate of patient death (28% in the belatacept group versus 36% in the CNI control group), active antibody-mediated rejection (6% versus 7%), T-cell-mediated rejection (4% versus 4%), major adverse cardiovascular events, and cancer occurrence (9% versus 11%). A significantly higher rate of de novo proteinuria was observed in the belatacept group as compared with the CNI control group (37% versus 21%, P < 0.001). This real-world evidence study shows that conversion to belatacept post-transplant was associated with lower risk of graft failure and acceptable safety outcomes compared with patients maintained on CNIs. Long-term Outcomes after Conversion to Belatacept, NCT04733131 .

Urinary Endotrophin and Long-term Outcomes in Kidney Transplant Recipients

Background. Kidney fibrosis is a suggested cause of kidney failure and premature mortality. Because collagen type VI is closely linked to kidney fibrosis, we aimed to evaluate whether urinary endotrophin, a collagen type VI fragment, is associated with graft failure and mortality among kidney transplant recipients (KTR). Methods. In this prospective cohort study, KTR with a functioning graft ≥1-y posttransplantation were recruited; 24-h urinary endotrophin excretion was measured using an ELISA method. Multivariate Cox regression analyses were performed. Results. A total of 621 KTR (mean age 53 y old, 43% female) at a median of 5.2 y posttransplantation were included. Median 24-h urinary endotrophin excretion was 5.6 (3.1–13.6) µg/24h. During a median follow-up of 7.5 y, 87 KTR (14%) developed graft failure and 185 KTR (30%) died; 24-h urinary endotrophin excretion was associated with increased risk of graft failure (hazard ratio [95% confidence interva] per doubling = 1.24 [1.08-1.42]) and all-cause mortality (hazard ratio [95% confidence intervals] per doubling = 1.14 [1.03-1.25]) independent of potential confounders including plasma endotrophin concentration. Twenty-four-hour urinary protein excretion was a significant effect modifier for the association with mortality (Pinteraction = 0.002). Twenty-four-hour urinary endotrophin excretion was only significantly associated with mortality in KTR with low levels of proteinuria. Conclusions. Urinary endotrophin is independently associated with an increased risk of graft failure in all KTR and mortality only in KTR with low levels of proteinuria. Further studies with different KTR populations are needed to confirm these findings.

The hepatocyte growth factor mimetic, ANG-3777, in kidney transplant recipients with delayed graft function: Results from a randomized phase 3 trial

In kidney transplant recipients, delayed graft function increases the risk of graft failure and mortality. In a phase 3, randomized, double-blind, placebo-controlled trial, we investigated the hepatocyte growth factor mimetic, ANG-3777 (once daily for 3 consecutive days, starting ≤30 hours posttransplant), in 248 patients receiving a first kidney transplant from a deceased donor. At day 360, estimated glomerular filtration rate (primary endpoint) was not significantly different between the ANG-3777 and placebo groups. There were no significant between-group differences in the duration of dialysis through day 30 or in the percentage of patients with an estimated glomerular filtration rate of >30 mL/min/1.73 m2 at day 360. The incidence of both delayed graft function and acute rejection was similar between ANG-3777 and placebo groups (68.5% vs 69.4% and 8.1% vs 6.5%, respectively). ANG-3777 was well tolerated, and there was a numerically lower incidence of graft failure versus placebo (3.2% vs 8.1%). Although there is insufficient evidence to support an indication of ANG-3777 for patients at risk of renal dysfunction after deceased-donor kidney transplantation, these findings indicate potential biological activity that may warrant further investigation.

Predictive factors for re-bubbling after DMEK: focus on the posterior corneal surface.

To understand whether the preoperative morphology of the posterior corneal surface influences the rate of re-bubbling after Descemet membrane endothelial keratoplasty (DMEK). After retrospectively analyzing the medical records of patients undergoing DMEK, in this multicentric cross-sectional study, we performed a binomial logistic regression analysis to assess significant predictors of re-bubbling and re-transplantation after surgery. Analyzed parameters included the preoperative diagnosis, anterior and posterior surface K1/K2, central corneal thickness, posterior Q value, and other posterior corneal surface parameters evaluated on the elevation maps produced by anterior segment optical coherence tomography. Results were stratified based on the surgeons' experience. We included 202 eyes of 202 patients with a mean age of 69.5 ± 12.4years; 154 eyes were operated by a high-volume surgeon and 48 by one with less experience; 48 eyes (23.8%) underwent 1 re-bubbling and 14(6.9%) 1 re-transplantation. The presence of positive/less-negative posterior corneal irregularities and irregularities with greater absolute height had a significantly higher risk of re-bubbling in both the expert and less expert group (OR = 2.85 and 1.42, OR = 3.22 and 3.01, respectively, p < 0.05), whereas more negative posterior K1 and K2 were significant risk factors only in the former group (OR = 0.67 and 0.55, respectively, p < 0.05). Endothelial decompensation other than Fuchs and pseudophakic bullous keratopathy, more negative posterior Q values and smaller distances between center, and the highest/lowest posterior corneal surface irregularity correlated with an increased risk of graft failure (OR 1.23, 1.21, and 1.29, respectively, p < 0.05). Posterior corneal surface morphology significantly influences the risk of re-bubbling after DMEK.

The Correlation Between Graft Size and Graft Failure in Hamstring Autograft Anterior Cruciate Ligament Reconstruction.

Previous studies have investigated various factors that contribute to graft failure in hamstring anterior cruciate ligament (ACL) reconstruction. However, there is debate about the potential advantages of increasing graft diameters beyond 8 mm. In this retrospective cohort study (level of evidence III), we investigated whether increasing graft sizes beyond 8 mm diameter showed any advantages in reducing the risk ofgraft failure. We utilized univariate Kaplan-Meier analysis and Cox proportional hazard (PH) regression models to compare the risk of failure in the different patient groups. Mutual adjustment was performed for age, gender, body mass index (BMI), and graft strands.Graft sizes ranging between 8 and 10 mm were assessed for their association with graft failure, alongside examining the impact of graft strands, age, and BMI on graft failure. A total of 487 patients underwent hamstring autograft ACL reconstruction at our hospital between January 2016 and December 2020. Our analysis indicated that among patients undergoing hamstring autograft ACL reconstruction, the risk of graft failure was 1.64 times higher for patients with a graft size between 8.5 and 9 mm (95% CI 0.36-7.43, p=0.483) and 2.19 times higher for patients with a graft size between 9.5 and 10.5 mm (95% CI 0.42-11.31, p=0.384) compared to those with an 8 mm graft. However, there was weak evidence against the null hypothesis. Conclusion: These findings suggest that there is no benefit to increasing graft sizes past 8 mm and that other factors, like surgical technique, should be considered when assessing the risk of graft failure in patients undergoing ACL reconstruction.

Change in Posterior Tibial Slope Angle After Displaced Pediatric Tibial Tubercle Fracture: A Model for Growth Modulation in the ACL-Deficient Knee.

Increased posterior tibial slope angle (PTSA) has been shown to be an important risk factor for anterior cruciate ligament (ACL) injury. PTSA modulation is not utilized routinely to reduce risk of primary rupture or graft failure. Displaced tibial tubercle (TT) fractures in the skeletally immature are associated with potential growth arrest and may be used as a model to study PTSA changes in this setting. To quantify the change in PTSA (ΔPTSA) after operative treatment of displaced TT fractures in skeletally immature patients. It was hypothesized that there would be a progressive decrease in PTSA after TT injury and that rate of ΔPTSA would be highest during peak growth velocity. Case series; Level of evidence, 4. Included were 22 patients (n = 23 knees; mean chronological and bone age at injury, 14 years; 86% male) who underwent surgery for displaced TT fracture. PTSA was measured on lateral radiographs at time of surgery and subsequent follow-up, and bone age at the time of injury was determined using radiographic standards. The rate of ΔPTSA for individual patient, total cohort, and sex-based subgroup trends were determined via linear regression (degrees per month; positive value indicates relatively anterior). Individual patient regression coefficients were averaged into bone age cohorts. Average follow-up was 17 months (range, 6-52 months). The mean PTSA was -12°± 2.4° at the time of injury, and the mean ΔPTSA for the cohort was 0.30°± 0.31° per month (range, -0.27° to 0.97° per month). Linear regression demonstrated a significant relationship between months postfixation and PTSA, demonstrating a ΔPTSA of 0.31° per month (95% confidence interval [CI], 0.24° to 0.38°; P < .001). The highest ΔPTSA was seen at bone age 14 years (mean, 0.58°± 0.44° per month). The mean absolute change in PTSA from injury to final follow-up was 4.1° (range, -3.4° to 21°). Our data suggested that PTSA becomes more anterior after operatively treated pediatric TT fractures and that ΔPTSA may be influenced by bone age. This concept may be useful in considering surgical modulation of excessive PTSA in the pediatric ACL-deficient knee.

Urinary vanin-1, tubular injury, and graft failure in kidney transplant recipients

We investigated whether urinary vascular non-inflammatory molecule-1 (vanin-1), a promising early-onset tubular injury marker, correlates with other established tubular injury markers and is associated with graft failure in kidney transplant recipients (KTR). We measured 24 h urinary vanin-1 excretion in 656 KTR (age 53 ± 13 years, 43% female, estimated glomerular filtration rate (eGFR) 53 ± 21 mL/min/1.73 m2) who had undergone kidney transplantation ≥ 1 year. The median 24 h urinary vanin-1 excretion was 145 [51–331] pmol/24 h. 24 h urinary vanin-1 excretion correlated weakly but significantly with other tubular injury markers (ρ = 0.14, p < 0.001 with urinary liver-type fatty acid binding protein, ρ = 0.13, p = 0.001 with urinary post-translationally modified fetuin-A protein, and ρ = 0.10, p = 0.011 with plasma neutrophil gelatinase-associated lipocalin) and with eGFR (ρ = − 0.13, p = 0.001). During a median follow-up of 7.4 [4.9–8.0] years, 94 (14%) KTR developed death-censored graft failure. In multivariable Cox regression analyses, 24 h urinary vanin-1 excretion was not associated with an increased risk of death-censored graft failure (adjusted hazard ratio [95% confidence interval] = 0.96 [0.86–1.07], p = 0.5). In conclusion, our findings do not support the role of urinary vanin-1 as a biomarker of graft failure after kidney transplantation.

Ensemble Clustering to Generate Phenotypes of Kidney Transplant Donors and Recipients.

In this paper we investigate the generation of phenotypes for kidney transplant donors and recipients to assist with decision making around organ allocation. We present an ensemble clustering approach for multi-type data (numerical and categorical) using two different clustering approaches-i.e., model based and vector quantization based clustering. These clustering approaches were applied to a large, US national deceased donor kidney transplant recipient database to characterize members of each cluster (in an unsupervised fashion) and to determine whether the subsequent risk of graft failure differed for each cluster. We generated three distinct clusters of recipients, which were subsequently used to generate phenotypes. Each cluster phenotype had recipients with varying clinical features, and the risk of kidney transplant graft failure and mortality differed across clusters. Importantly, the clustering results by both approaches demonstrated a significant overlap. Utilization of two distinct clustering approaches may be a novel way to validate unsupervised clustering techniques and clustering can be used for organ allocation decision making on the basis of differential outcomes.

Scoring donor lungs for graft failure risk: The Lung Donor Risk Index (LDRI)

Lung transplantation lags behind other solid organ transplants in donor lung utilization due, in part, to uncertainty regarding donor quality. We sought to develop an easy-to-use donor risk metric that, unlike existing metrics, accounts for a rich set of donor factors. Our study population consisted of n = 26 549 adult lung transplant recipients abstracted from the United Network for Organ Sharing Standard Transplant Analysis and Research file. We used Cox regression to model graft failure (GF; earliest of death or retransplant) risk based on donor and transplant factors, adjusting for recipient factors. We then derived and validated a Lung Donor Risk Index (LDRI) and developed a pertinent online application (https://shiny.pmacs.upenn.edu/LDRI_Calculator/). We found 12 donor/transplant factors that were independently predictive of GF: age, race, insulin-dependent diabetes, the difference between donor and recipient height, smoking, cocaine use, cytomegalovirus seropositivity, creatinine, human leukocyte antigen (HLA) mismatch, ischemia time, and donation after circulatory death. Validation showed the LDRI to have GF risk discrimination that was reasonable (C = 0.61) and higher than any of its predecessors. The LDRI is intended for use by transplant centers, organ procurement organizations, and regulatory agencies and to benefit patients in decision-making. Unlike its predecessors, the proposed LDRI could gain wide acceptance because of its granularity and similarity to the Kidney Donor Risk Index.

Twelve Thousand Kidney Transplants Over More Than 55 Y: A Single-center Experience.

Kidney transplant outcomes have dramatically improved since the first successful transplant in 1954. In its early years, kidney transplantation was viewed more skeptically. Today it is considered the treatment of choice among patients with end-stage kidney disease. Our program performed its first kidney transplant in 1966 and recently performed our 12 000th kidney transplant. Here, we review and describe our experience with these 12 000 transplants. Transplant recipients were analyzed by decade of date of transplant: 1966-1975, 1976-1985, 1986-1995, 1996-2005, 2006-2015, and 2016-2022. Death-censored graft failure and mortality were outcomes of interest. Of 12 000 kidneys, 247 were transplanted from 1966 to 1975, 1147 from 1976 to 1985, 2194 from 1986 to 1995, 3147 from 1996 to 2005, 3046 from 2006 to 2015, and 2219 from 2016 to 2022 compared with 1966-1975, there were statistically significant and progressively lower risks of death-censored graft failure at 1 y, 5 y, and at last follow-up in all subsequent eras. Although mortality at 1 y was lower in all subsequent eras after 1986-1995, there was no difference in mortality at 5 y or the last follow-up between eras. In this large cohort of 12 000 kidneys from a single center, we observed significant improvement in outcomes over time. Kidney transplantation remains a robust and ever-growing and improving field.

The Association of Post-Lung Transplant Pulmonary Embolism With the Development of Chronic Lung Allograft Dysfunction.

Pulmonary embolism (PE) is a rare yet serious postoperative complication for lung transplant recipients (LTRs). The association between timing and severity of PE and the development of chronic allograft lung dysfunction (CLAD) has not been described. A single-center, retrospective cohort analysis of first LTRs included bilateral or single lung transplants and excluded multiorgan transplants and retransplants. PEs were confirmed by computed tomography angiography or ventilation/perfusion (VQ) scans. Infarctions were confirmed on computed tomography angiography by a trained physician. The PE severity was defined by the Pulmonary Embolism Severity Index (PESI) score, a 30-d post-PE mortality risk calculator, and stratified by low I and II (0-85), intermediate III and IV (85-125), and high V (>125). PE and PESI were analyzed in the outcomes of overall survival, graft failure, and chronic lung allograft dysfunction (CLAD). We identified 57 of 928 patients (6.14%) who had at least 1 PE in the LTR cohort with a median follow-up of 1623 d. In the subset with PE, the median PESI score was 85 (75.8-96.5). Most of the PESI scores (32/56 available) were in the low-risk category. In the CLAD analysis, there were 49 LTRs who had a PE and 16 LTRs (33%) had infarction. When treating PE as time-dependent and adjusting for covariates, PE was significantly associated with death (hazard ratio [HR] 1.8; 95% confidence interval [CI], 1.3-2.5), as well as increased risk of graft failure, defined as retransplant, CLAD, or death (HR 1.8; 95% CI, 1.3-2.5), and CLAD (HR 1.7; 95% CI, 1.2-2.4). Infarction was not associated with CLAD or death. The PESI risk category was not a significant predictor of death or CLAD. PE is associated with decreased survival and increased hazard of developing CLAD. PESI score was not a reliable predictor of CLAD or death in this lung transplant cohort.

Mismatched Postsurgical Opioid Prescription to Liver Transplant Patients: A Retrospective Cohort Study From a Single High-volume Transplant Center.

Improper opioid prescription after surgery is a well-documented iatrogenic contributor to the current opioid epidemic in North America. In fact, opioids are known to be overprescribed to liver transplant patients, and liver transplant patients with high doses or prolonged postsurgical opioid use have higher risks of graft failure and death. This is a retrospective cohort study of 552 opioid-naive patients undergoing liver transplant at an academic center between 2012 and 2019. The primary outcome was the discrepancy between the prescribed discharge opioid daily dose and each patient's own inpatient opioid consumption 24 h before discharge. Variables were analyzed with Wilcoxon and chi-square tests and logistic regression. Opioids were overprescribed in 65.9% of patients, and 54.3% of patients who required no opioids the day before discharge were discharged with opioid prescriptions. In contrast, opioids were underprescribed in 13.4% of patients, among whom 27.0% consumed inpatient opioids but received no discharge opioid prescription. The median prescribed opioid daily dose was 333.3% and 56.3% of the median inpatient opioid daily dose in opioid overprescribed and underprescribed patients, respectively. Importantly, opioid underprescribed patients had higher rates of opioid refill 1 to 30 and 31 to 90 d after discharge, and the rate of opioid underprescription more than doubled from 2016 to 2019. Opioids are both over- and underprescribed to liver transplant patients, and opioid underprescribed patients had higher rates of opioid refill. Therefore, we proposed to prescribe discharge opioid prescriptions based on liver transplant patients' inpatient opioid consumption to provide patient-centered opioid prescriptions.

Association of metformin with cardiovascular and graft outcomes in kidney transplant recipients with posttransplantation diabetes mellitus.

Posttransplantation diabetes mellitus (PTDM) is a crucial problem after kidney transplantation. We aimed to determine whether metformin affects cardiovascular and graft outcomes in patients with PTDM. This retrospective cohort study included 1,663 kidney transplant recipients without preexisting diabetes mellitus. The patients were divided into metformin and non-metformin groups, with matched propensity scores. We also estimated metformin's effect on percutaneous coronary intervention (PCI), major adverse cardiovascular events (MACEs), acute rejection, and graft failure. Of 634 recipients with PTDM, 406 recipients were treated with metformin. The incidence of PCI was 2.4% and 7.1% in the metformin and non-metformin groups, respectively (p = 0.04). The metformin group exhibited a lower risk of PCI in Cox regression analyses (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.10-0.77; p = 0.014), especially in subgroups with male sex, age over 49 years (median), long-term metformin use (mean of ≥1,729 days), and simultaneous tacrolimus administration. Long-term metformin use was also associated with lower incidence of MACEs (HR, 0.09; 95% CI, 0.01-0.67; p = 0.02). Incidence of graft failure was 9.9% and 17.0% in the metformin and non-metformin groups, respectively (p = 0.046). Both long-term use and higher dose of metformin, as well as tacrolimus administration with metformin, were associated with a lower risk of graft failure (HR, 0.29; 95% CI, 0.11-0.75; p = 0.01; HR, 0.39; 95% CI, 0.18-0.85; p = 0.02; and HR, 0.39; 95% CI, 0.19-0.79; p = 0.009, respectively). Metformin use is associated with a decreased risk of developing coronary artery disease and better graft outcomes in PTDM.