Previous Rejection Research Articles

Management of the vaccination campaign in a population of frail older outpatients affected by cognitive or endocrinological conditions: a pilot study in Italy

Vaccination, particularly against pneumococcus and influenza, is a low-cost primary prevention, useful to avoid hard complications, particularly among frail older people. In this pilot study, we aimed to assess the effect of a strategy for influenza and pneumococcal vaccination for outpatients mainly affected by cognitive or endocrinological conditions, evaluating what could stimulate or demotivate vaccination among older people. This study was conducted during the 2023–2024 influenza season at the outpatient clinics in Palermo, Italy. A total 76 patients were included. More than half of the patients could be considered as pre-frail and about 20% frail, according to a comprehensive geriatric evaluation. Among patients, 46.05% received only vaccination against pneumococcus, 28.95% both vaccinations, and 25.0% only against influenza. Compared with the previous seasons, a 19.5% increase of influenza and 90.2% of pneumococcal vaccine uptake was observed. Side effects of vaccination were the main reason of the previous rejection, namely 76.9% for influenza and 53.8% for anti-pneumococcal vaccination. In conclusion, our study indicates how a new vaccination strategy in different settings could be feasible. Proposing influenza and pneumococcal vaccination for frail older outpatients could be an effective instrument to improve immunization coverage that is still low among older people.

#1654 Infectious complications after kidney transplantation: a retrospective study

Abstract Background and Aims Infection is a major cause of morbidity among kidney transplant recipients. Allograft rejection is a frequent cause of dysfunction and its treatment increases the risk for both common and opportunistic infections. Nevertheless, its exact impact on infection incidence and further worsening of allograft dysfunction is not fully known. We aimed to characterize the incidence, nature, and severity of infectious complications following kidney transplantation, their association with previous rejection and its impact on allograft function. Method This was a single center retrospective study covering all patients transplanted between July 2021 and June 2023 in a tertiary referral center. Demographic and clinical data were collected from patient records, including donor and patient features, graft function over time and occurrence of either infection or rejection. Logistic regressions were adjusted considering sex, age, blood type and presence of diabetes as independent variables. Results A total of 139 patients were considered, 49 (35.3%) were women and 90 (64.7%) were men. Mean age was 49.6 ± 13.0 years. Median follow-up time was 375 [194-596] days. The main cause of renal disease was diabetes (37 patients, 26.8%) and most patients (113; 81.9%) were on hemodialysis for a median vintage of 3 [2.3] years. Considering the 139 transplants performed, 113 (81.2%) were isolated kidney, 24 (17.4%) were simultaneous kidney-pancreas and 2 (1.4%) were simultaneous kidney-liver transplantation. Eleven (7.9%) were living donor. During follow-up time, in-hospital infection occurred in 34 (24.4%) patients, mostly urinary (13, 38%) and blood stream (11, 32%) infections. These events significantly delayed hospital discharge (15.88 ± 8.52 vs 26.05 ± 14.3 days, p-value=0.001). During the follow up, a total of 107 (77%) patients developed 220 infection episodes leading to 47 hospital admissions. Urinary infections (64, 28.8%) and cytomegalovirus (CMV) viremia (64, 28.8%) were the most common at median follow-up time of 85.5 [40.25-183.75] and 159 [43.25-258.5] days, respectively. Median timing of diagnosis was 400.8 [203-614] days after transplant. They were much more common during the first three months (0.014 vs 0.002 per follow-up day). There were no differences in infection incidence between type of donor (p=0.76), type of allograft (p=0.361), immunosuppression protocol (thymoglobulin or basiliximab, p=0.45), renal replacement therapy or presence of diabetes. Regarding urinary infections, days of urinary catheterization (p=0.905), need for catheter replacement (p=0.092) or presence of residual diuresis (p=0.375) had no impact on infection rates. A positive correlation was found, between the number of infection episodes and creatinine increase over the first year (r=0.386; p<0.000). Allograft rejection was diagnosed and treated through protocol biopsy in 25 (18%) cases. These patients presented 17 confirmed episodes of infection over the three following months. Nine of them (36%) were CMV detectable viremias. Patients with a history of rejection had significantly more infections (1.49 ± 1.22 vs 2.20 ± 1.26, p=0.01), even after adjustment (p=0.006). Conclusion Early infections after kidney transplantation negatively impact hospital length of stay and allograft function. Furthermore, immunosuppressive treatment of allograft rejection carries a higher risk of infection. Further research is needed to clarify the impact of specific subsets of allograft rejection and immunosuppression protocols on the incidence of various types of infectious complications which could impair short-term renal function.

COVID-19 vaccination and corneal allograft rejection- a review.

To provide a comprehensive literature review on the perceived correlation between COVID-19 vaccination and corneal allograft rejection, and to characterize risk factors, time course, graft outcomes and proposed immunological basis. A literature review was conducted in August 2023 using 4 electronic databases: PubMed, EMBASE, MEDLINE and Scopus. Articles were sourced using key words associated with COVID-19 vaccination and corneal graft. All articles were screened for relevance by abstract review. Duplicates and articles related to COVID-19 infection were excluded. No time limits were set. Additional literature searches regarding cause of corneal graft rejection, rates of graft rejection associated with other vaccines and the cellular mechanism of rejection were also performed. 262 articles were identified from the literature search. 37 papers were included in the analysis based on defined inclusion criteria. This consisted of systematic reviews (n=6), review articles (n=5), retrospective studies (n=3), case series (n=8), letter to the editor (n=1) and case reports (n= 14). The majority of reported allograft rejections were in penetrating keratoplasties. Risk factors for COVID-19 vaccination associated rejection were previous allograft rejection episodes, repeat grafts and penetrating keratoplasty. Most reported rejection episodes were mild and resolved with treatment. Notably, several studies reported nil increase in corneal allograft rejection episodes over the COVID-19 vaccination period. Rejection episodes are associated with a broad spectrum of other vaccines and the complete pathophysiology is undetermined. Corneal allograft rejection appears to be a rare complication of COVID-19 vaccination most frequently observed in high-risk corneal transplants. The true extent of this correlation remains controversial; however, clinician awareness of this risk is essential to its mitigation. Patient counselling around symptom monitoring following vaccination and discussion around topical steroid prophylaxis may be prudent.

Online multiple hypothesis testing.

Modern data analysis frequently involves large-scale hypothesis testing, which naturally gives rise to the problem of maintaining control of a suitable type I error rate, such as the false discovery rate (FDR). In many biomedical and technological applications, an additional complexity is that hypotheses are tested in an online manner, one-by-one over time. However, traditional procedures that control the FDR, such as the Benjamini-Hochberg procedure, assume that all p-values are available to be tested at a single time point. To address these challenges, a new field of methodology has developed over the past 15 years showing how to control error rates for online multiple hypothesis testing. In this framework, hypotheses arrive in a stream, and at each time point the analyst decides whether to reject the current hypothesis based both on the evidence against it, and on the previous rejection decisions. In this paper, we present a comprehensive exposition of the literature on online error rate control, with a review of key theory as well as a focus on applied examples. We also provide simulation results comparing different online testing algorithms and an up-to-date overview of the many methodological extensions that have been proposed.

Prognostic value of right ventricular three-dimensional speckle-tracking strain in adult heart transplantation patients.

We aimed to investigate the prognostic value of three-dimensional right ventricular free wall longitudinal strain (3D-RV FWLS) in adult heart transplantation (HTx) patients, taking three-dimensional left ventricular global longitudinal strain (3D-LV GLS) into account. We prospectively enrolled 155 adult HTx patients. Conventional right ventricular (RV) function parameters, two-dimensional (2D) RV FWLS, 3D-RV FWLS, RV ejection fraction (RVEF), and 3D-LV GLS were obtained in all patients. All patients were followed for the endpoint of death and major adverse cardiac events. After a median follow-up of 34months, 20 (12.9%) patients had adverse events. Patients with adverse events had higher incidence of previous rejection, lower hemoglobin, and lower 2D-RV FWLS, 3D-RV FWLS, RVEF and 3D-LV GLS (P < 0.05). In multivariate Cox regression, Tricuspid annular plane systolic excursion (TAPSE), 2D-RV FWLS, 3D-RV FWLS, RVEF and 3D-LV GLS were independent predictors of adverse events. The Cox model using 3D-RV FWLS (C-index = 0.83, AIC = 147) or 3D-LV GLS (C-index = 0.80, AIC = 156) was observed to predict adverse events more accurately than that with TAPSE, 2D-RV FWLS, RVEF or traditional risk model. Moreover, when added in nested models including previous ACR history, hemoglobin levels, and 3D-LV GLS, the continuous NRI (0.396, 95% CI 0.013 ~ 0.647; P = 0.036) of 3D-RV FWLS was significant. 3D-RV FWLS is a stronger independent predictor of adverse outcomes, and provides additive predictive value over 2D-RV FWLS and conventional echocardiographic parameters in adult HTx patients, taking 3D-LV GLS into account.

Kidney Allograft Rejection and Coronavirus Disease 2019 Infection: A Narrative Review.

The world has experienced a global medical and socioeconomic burden following the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 is a systemic disease and may affect different organs including the kidneys. Current literature contains reports on COVID-19-related conditions such as acute kidney injury, and complications experienced by chronic kidney disease, end stage kidney disease, and kidney transplant patients. Here, we discuss the incidence of kidney allograft rejection, immunosuppression management and rejection risk, donor-specific antibodies and previous rejection episodes, and rejection outcomes in kidney transplant recipients with COVID-19 by reviewing current studies.

Outcomes of Non-Myeloablative HLA-Haploidentical Bone Marrow Transplant with Thiotepa and Post-Transplant Cyclophosphamide in Children and Adults with Sickle Cell Disease, a Phase II Trial: Vanderbilt Global Haploidentical Transplant Learning Collaborative (VGC2)

Introduction: Related reduced-intensity HLA-Haploidentical bone marrow transplant (haplo-BMT) expands the donor pool to approximately 90% of children and adults with sickle cell disease (SCD). In 2013, we developed the multi-institutional Vanderbilt Global Haploidentical Learning Collaborative to optimize haplo-BMT for SCD. In a Phase II clinical trial, we developed a protocol focused on improving engraftment rates by augmenting the original Hopkins haplo-BMT approach (Bolaños-Meade et al. Blood 2012) with thiotepa. We initially demonstrated durable engraftment in 93% (14/15) of participants (including 2 with previous graft rejection) and a 100% overall survival after a median follow-up of 13.3 months (de la Fuente et al. BBMT 2019). We present the results of our phase-II trial (ClinicalTrials.gov identifier NCT01850108). Material and methods: The trial opened in October 2013, and each site has a standalone Institutional Review Board-approved protocol with institutional-specific eligibility criteria and a data-sharing agreement with Vanderbilt University Medical Center. A DSMB assessed the aggregate results for participant safety and clinical trial futility. Collaborators met via videoconferencing initially weekly and then bi-weekly to discuss best practices. The common conditioning regimen included: thymoglobulin 4.5 mg/kg, thiotepa 10 mg/kg, fludarabine 150 mg/m2, cyclophosphamide 29 mg/kg and TBI 2Gy. Graft-versus-host disease (GVHD) prophylaxis included post-transplant cyclophosphamide 100 mg/kg, mycophenolate mofetil, and sirolimus. Bone marrow was the donor source and was primed with filgrastim (5-10 μg/kg/d x5 days) in 11% (9/80) of haploidentical donors. Primary and secondary graft failure was defined as <5% donor myeloid/lymphoid whole blood chimerism at Day>28 and >Day+28 (after initial engraftment), respectively. Primary endpoints were 1-year and 2-year EFS. Primary or secondary graft failure and death were considered events. Safety stopping rules were implemented, independent of age, based on graft failure, death, grade III or IV acute GVHD, or moderate or severe chronic GVHD. Local treating physicians classified the severity of chronic GVHD. Results: At the interim analysis of May 1, 2022, we report results from patients enrolled from 8/14/2014 - 2/28/2022. Final enrollment is a total of 80 participants from 7 sites, 45% were male. Donors were siblings (42.5%), parents (53.8%), daughters (2.5%) and cousins (1.3%); 83.8% (n=67) had sickle cell trait. Participants clinical and laboratory data are listed in table 1. Graft failure occurred in 12.5% (10/80) of the participants, with 4 primary and 6 secondary graft failures, table 2. All graft failures were in participants <18 years of age, and all had autologous reconstitution. For engrafted participants, the median whole blood chimerism values for D+180 and D+365 post-transplant was 100% (n=67; IQR: 99.8 - 100; Range 30.0 - 100) and 100% (n=50; IQR: 100 - 100; Range 95.0 - 100), respectively. Among engrafted participants, 97.7% (43/44) were off immunosuppression at D+365 post-transplant. The incidence of grades III-IV acute and moderate/severe chronic GVHD were 8.8% (7/80) each. The median follow-up time was 1.4 years, based on the time of graft failure, death, or May 1, 2022. Mortality was 5.0% (4/80), Table 2. A Kaplan-Meier analysis for survival found no difference by age group <18 years or >18 years of age (p=0.760). Kaplan-Meier based probability of overall survival was 96.7% (95% CI 87.1% - 99.2%) at one year and 94.3% (95% CI 83.0% - 98.2%) at two years. Results of the final analysis of primary and secondary endpoints (1- and 2-year EFS) will be submitted for publication after all participants have been followed for a minimum of one year (anticipated 2/23). Conclusion: Our Vanderbilt Global Haploidentical learning collaborative is a successful and efficient approach to sharing best practices and implementing curative therapy for SCD. After 8 years, we have shown low mortality rate and 100% engraftment in adults using our haplo-BMT regimen. Three new research questions have emerged in the consortium: 1. What strategies can we develop to address the high graft failure in children? 2. How can we optimize supportive care practices and minimize severe infectious complications in adults? 3. What are the heart, lung, kidney, and other late-health effects after curative therapy? Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

T1 mapping of the right ventricle in heart transplant recipients: how does it correlate with endomyocardial biopsy findings?

Abstract Aim Noninvasive detection of cardiac allograft rejection is highly desirable. We sought to assess how right ventricular (RV) T1 mapping correlates with endomyocardial biopsy findings. Methods All patients underwent right heart catheterization with biopsy and cardiac magnetic resonance (CMR) irrespective of symptoms, as part of the institutional registry protocol dedicated to heart transplant (HTx) recipients. CMR studies were performed using a 1.5 T scanner and analyses by using a commercially available software (CMR42, Circle CVI, Calgary, Canada). Endocardial and epicardial borders were drawn on end-systolic and end-diastolic phases for ventricular function analysis. For T1 measurements, region of interests located at the RV free-wall were drawn manually on midventricular short-axis slices avoiding blood pool and epicardial fat. Extracellular volume (ECV) was calculated as ECV = (1 − hematocrit) × (ΔR1 myocardium/ΔR blood), where R1 = 1/T1. Late gadolinium enhancement (LGE) images were also obtained using a phase-sensitive inversion recovery segmented gradient echo sequence. Hyperenhancement was assessed semi-quantitatively as segmental (2–3 cm) or diffuse (&amp;gt;3 cm). Allograft rejection was determined based on the severity of inflammatory infiltrates and myocyte damage on pathological specimens according to the standardized International Society for Heart and Lung Transplantation (ISHLT) nomenclature. Results In all, 61 paired studies were evaluated. None of the patients had heart failure symptoms. We defined 3 subgroups: Group I; never rejected (n=23), group II; biopsy remarkable for rejection (n=19) and group III; history of past rejection(s) (n=19). RV volumes and ejection fraction (EF) did not differ between the groups. However, rejections were nicely mirrored by T1 time and particularly by ECV. Of note, T1 time and ECV improved but not completely normalized after resolution of rejection. Overall, T1 time (cut off 1060ms) and ECV (cut off 35%) were sensitive (84%, both) and had high negative predictive values (88% and 87%, respectively) but not specific (43% and 52% respectively) for discriminating rejection related subclinical RV damage. Their specificity slightly improved to 52 and 61% respectively, if patients with previous rejection were excluded (Figure 1). LGE did not discriminate rejection. Conclusion RV volumes and EF are insensitive to detect allograft rejection. Native T1 time and ECV of the RV, as a means of extracellular expansion, likely reflect interstitial fibrosis, oedema, and inflammation that are typical for, but not limited to allograft rejection. Hence, these parameters can help to exclude rejection but have limited standalone value for making the nonivasive diagnosis due to their low specificity. These results cannot be extrapolated to the left ventricle. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): University of Baskent

Impact of Managed Entry Agreements on availability of and timely access to medicines: an ex-post evaluation of agreements implemented for oncology therapies in four countries

BackgroundDespite the increased utilisation of Managed Entry Agreements (MEAs), empirical studies assessing their impact on achieving better access to medicines remains scarce. In this study we evaluated the role of MEAs on enhancing availability of and timely access to a sample of oncology medicines that had received at least one prior rejection from reimbursement.MethodsFunding decisions and their respective timelines for all oncology medicines approved between 2009 and 2018 in Australia, England, Scotland and Sweden were studied. A number of binary logit models captured the probability (Odds ratio (OR)) of a previous coverage rejection being reversed to positive after resubmission with vs. without a MEA. Gamma generalised linear models were used to understand if there is any association between time to final funding decision and the presence of MEA, among other decision-making variables, and if so, the strength and direction of this association (Beta coefficient (B)).ResultsOf the 59 previously rejected medicine-indication pairs studied, 88.2% (n = 45) received a favourable decision after resubmission with MEA vs. 11.8% (n = 6) without. Average time from original submission to final funding decision was 404 (± 254) and 452 (± 364) days for submissions without vs. with MEA respectively. Resubmissions with a MEA had a higher likelihood of receiving a favourable funding decision compared to those without MEA (43.36 < OR < 202, p < 0.05), although approval specifically with an outcomes-based agreement was associated with an increase in the time to final funding decision (B = 0.89, p < 0.01). A statistically significant decrease in time to final funding decision was observed for resubmissions in Australia and Scotland compared to England and Sweden, and for resubmissions with a clinically relevant instead of a surrogate endpoint.ConclusionsMEAs can improve availability of medicines by increasing the likelihood of reimbursement for medicines that would have otherwise remained rejected from reimbursement due to their evidentiary uncertainties. Nevertheless, approval with a MEA can increase the time to final funding decision, while the true, added value for patients and healthcare systems of the interventions approved with MEAs in comparison to other available interventions remains unknown.

No evidence of moral licensing in a laboratory bribe-taking task

Moral licensing posits that previous moral acts increase the probability of behaving immorally in the future. According to this perspective, rejecting bribes, even because they are too small, would create a kind of “license” for taking (presumably larger) bribes in the future. On the other hand, the desire for consistency in behavior predicts that previous rejection of bribes will increase the probability of rejection for bribes offered in the future. Using a laboratory task modeling the decision to take a bribe, we examined how resisting and succumbing to the temptation to take a bribe affects later bribe-taking. Participants (N = 297) were offered either low bribes first and high bribes later or vice versa. Low bribes were in general rejected more often and the results showed some weak, nonsignificant evidence that bribe-taking may be influenced by the order of the sizes of offered bribes. However, there was no evidence of an increased probability of taking bribes after being offered the low bribes first and thus no evidence in support of the moral licensing effect.

Donor-derived Cell-free DNA Measurement in Kidney Transplant Patients Without Allograft Dysfunction: More Evidence and More Questions.

Donor-derived Cell-free DNA Measurement in Kidney Transplant Patients Without Allograft Dysfunction: More Evidence and More Questions.

Approach to optimal assessment of right ventricular remodelling in heart transplant recipients: insights from myocardial work index, T1 mapping, and endomyocardial biopsy.

Right ventricular (RV) dysfunction is an important cause of graft failure after heart transplantation (HTx). We sought to investigate relative merits of echocardiographic tools and cardiac magnetic resonance (CMR) with T1 mapping for the assessment of functional adaptation and remodelling of the RV in HTx recipients. Sixty-one complete data set of echocardiography, CMR, right heart catheterization, and biopsy were obtained. Myocardial work index (MWI) was quantified by integrating longitudinal strain (LS) with invasively measured pulmonary artery pressure. CMR derived RV volumes, T1 time, and extracellular volume (ECV) were quantified. Endomyocardial biopsy findings were used as the reference standard for myocardial microstructural changes. In HTx recipients who never had a previous allograft rejection, longitudinal function parameters were lower than healthy organ donors, while ejection fraction (EF) (52.0 ± 8.7%) and MWI (403.2 ± 77.2 mmHg%) were preserved. Rejection was characterized by significantly reduced LS, MWI, longer T1 time, and increased ECV that improved after recovery, whereas RV volumes and EF did not change MWI was the strongest determinant of rejection related myocardial damage (area under curve: 0.812, P < 0.0001, 95% CI: 0.69-0.94) with good specificity (77%), albeit modest sensitivity. In contrast, T1 time and ECV were sensitive (84%, both) but not specific to detect subclinical RV damage. Subclinical adaptive RV remodelling is characterized by preserved RV EF despite longitudinal function abnormalities, except for MWI. While ultrastructural damage is reflected by MWI, ECV, and T1 time, only MWI has the capability to discriminate functional adaptation from transition to subclinical structural damage.

FC 113: Development and Validation of an Integrative DD-CFDNA System to Predict Allograft Rejection: A Population Based Study

Abstract BACKGROUND AND AIMS Post-transplantation patient care requires development and validation of noninvasive biomarkers to improve allograft monitoring and prevention from unnecessary biopsies. Preliminary reports have suggested the association of donor derived cell-free DNA (dd-cfDNA) with allograft rejection. However, there is no proof of its added value beyond standard of care patient management in large and deep phenotyped cohorts. METHOD A total of 1210 concomitant evaluations of allograft histology, anti-HLA DSA and functional parameters between 2013 and 2018 were included corresponding to 637 evaluations in the derivation cohort and 573 in the validation cohort. dd-cfDNA was measured in plasma at the time of the evaluation. Diagnoses were assessed using Banff 2019 criteria. Parameters associated with kidney allograft rejection were assessed using uni- and multivariable logistic regression. We developed a risk model using the variables that were independently associated with rejection. RESULTS Higher levels of dd-cfDNA were observed for AMR and TCMR or both compared to other diagnoses (Figure 1A). We found incremental dd-cfDNA levels with increasing Banff lesion scores for g, ptc, i, t, cg and C4d (Figure 1B). There was no association of dd-cfDNA levels with allograft inactive lesions. In multivariable analysis, dd-cfDNA (P &amp;lt; 0.0001) was associated with kidney allograft rejection independently of DSA (P &amp;lt; 0.0001), eGFR (P = 0.018), kidney allograft instability (P = 0.013) and previous rejection (P &amp;lt; 0.0001). Based on these parameters, we built an integrative idd-cfDNA model that showed good discrimination (AUC: 0.83), good calibration and added value beyond a model without dd-cfDNA (AUC of the model without dd-cfDNA: 0.77 versus 0.83 for the integrative model; P &amp;lt; 0.0001). We confirmed our results in the validation cohort with a good discrimination (AUC: 0.82) and a good calibration. This integrative score, including the dd-cfDNA, is being validated in Belgium and in the USA. CONCLUSION We demonstrate the independent and added value of dd-cfDNA in addition to conventional features to predict rejection. This first integrative system shows improved performance for patient monitoring and could help physicians in decision-making process.

Cataract Surgery Results after Penetrating Keratoplasty

Objective. To compare clinical and refractive outcomes of cataract surgery by phacoemulsification and by extracapsular cataract extraction with implantation of foldable and rigid intraocular lenses in patients previously having undergone penetrating keratoplasty (PK).Patients and methods. This is a retrospective study. Medical records of all patients admitted for cataract surgery between 2010 and 2018 to the King Abdullah University Hospital (KAUH) were reviewed and medical records of patients who underwent cataract surgery after PK were analyzed. Medical records of 95 patients (58 males and 37 females; average age 40.0 ± 19.9 years) were selected. Depending upon the type of surgical technique applied, the cases were divided into two groups: first group included 60 patients who underwent cataract surgery by phacoemulsification with implantation of different foldable intraocular lenses (IOL), the second group included 35 patients who underwent cataract surgery by extracapsular cataract extraction (ECCE) with implantation of a polymethylmethacrylate (PMMA) IOL. The choice of ECCE technique with implantation of rigid IOLs was made if the endothelial cell density after PK was less than 2200 cells/mm2 and cataracts were of 4 and 5 grades to exclude additional trauma to the endothelium by ultrasound energy. Demographic and clinical data were collected. The R statistical program and SPSS were used for data analysis. The P value &lt; 0.05 was considered statistically significant.Results. Analysis showed that PK was performed mainly due to 4 indications: keratoconus (KC) — 77 % cases, herpetic keratopathy — 7 % cases, Eye trauma — 5 % cases, previous graft rejection — 5 % cases and Stevens–Johnson syndrome — 1 % cases. The mean best corrected visual acuity (BCVA) in the first group improved from 0.40 ± 0.05 to 0.80 ± 0.05 postoperatively. The mean BCVA in the second group improved from 0.30 ± 0.05 to 0.70 ± 0.05. In the late postoperative period BCVA with foldable IOLs was higher by 0.10 ± 0.05, as compared with the results obtained with the rigid IOLs. Mean intraocular pressure (IOP) changed from 15.1 ± 4.9 before PK to 16.3 ± 5.3 after PK.Conclusion. KC was the most common indication for PK in Jordan. Results of our analysis showed that cataract surgery could be successfully performed in eyes after PK with favorable results and improvement in patients’ quality of life. Cataract surgery by phacoemulsification with implantation of foldable IOLs results in higher (BCVA) compared to ECCE with implantation of PMMA IOLs. Unless contraindicated otherwise, phacoemulsification technique with foldable IOL implantation should be given preference over ECCE with implantation of rigid PMMA IOLs in visual rehabilitation of cataract patients after PK.

Role of Immunosuppression on Efficacy of Anti-SARS-CoV-2 Vaccines in Heart Transplanted (HT) Patients

PurposeVaccines against COVID-19 have a lower efficacy in HT patients (pts); factors influencing their immunogenicity are unknown. The aim of this study is to investigate the role of immunosuppression on mRNA vaccines efficacy.MethodsWe included all HT pts followed in our Center completing the vaccine cycle (03-06/21), for whom levels of IgG anti-RBD after the second dose were known, excluding those with a previous COVID infection. Demography, immunosuppression (drugs and trough blood level), lymphocyte count, previous rejection episodes were collected before the first dose. The endpoint was vaccine-induced immunization after the second dose according to our laboratory's threshold of IgG anti-RBD.ResultsAmong 201 vaccinated, IgG anti-RBD values were available for 63 pts at 2± 1 months after the second dose (22±3 days after the first; 89% BNT162b2; 60±11 yrs, 5±1 yrs from HT, 75% males, 3 with rejection > 1R in the previous 6 months). All pts were on CNI-inhibitors (35% tacrolimus, TAC, 65% cyclosporine, CyA), 57% on MMF, 23% mTOR, 69% steroids (CS). 41.7% had no response to vaccine. At univariate analysis the predictors of lack of response to vaccine were: MMF (43% vs 71%), TAC vs CSA (27% vs 73%), steroids (46% vs 76%), steroid dose > 5mg, lymphocytes <18% of leukocytes (both identified by ROC), more than 5 years from HT; mTOR was more likely associated with protection (80% vs 49%), p<0.05 all. Importantly, age was not predictive of immunogenicity. At stepwise multivariate analysis all these factors maintained statistical significance (p<0.05 all). IgG anti-RBD values were influenced by low lymphocytes, steroids and TAC trough levels (p< 0.05 all).Response to vaccine was the lowest for MMF+TAC+CS (23.1%), intermediate for MMF+CyA+CS (53.3%) and steroid-free regimens (68.7%), highest (87.5%) for mTOR+CNI+CS (20%,23%,24%,23% of pts, p=0.01). No rejection episodes were registered 3 months after the second dose of vaccine.ConclusionWhile confirming a low response to COVID-19 vaccines a in HT pts, our study underscores the negative effect of immunosuppression, particularly of MMF, high doses of steroids and TAC. Given that MMF is a cornerstone of most protocols, from these results it arises the hypothesis (to be tested in larger studies) if switching stable patients from TAC to Cya or to lower steroid doses may favor the attempts to increase the response to vaccines.

COVID-19 Vaccine Triggered Rejection in Lung Transplant Recipients: A Case Series

PurposeAnti-severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) vaccination is recommended by AST, ISHLT, and CDC in all transplant recipients. Lung transplant recipients (LTR) are at a higher risk of developing severe symptoms due to higher immunosuppression (IS) and baseline compromised graft function. Limited antibody response to messenger RNA (mRNA) vaccines has been reported in LTR, with the majority mounting a response after the 2nd dose. In this series, 3 patients developed new and significant respiratory compromise after their 2nd vaccine dose consistent with antibody mediated rejection (AMR). To our knowledge, this is the first published case series of vaccine induced rejection in LTR.MethodsRetrospective chart review of our cohort showed 46% fully vaccinated and an additional 2.5% partially vaccinated patients. Three fully vaccinated patients with approved mRNA vaccines (2 Moderna, 1 Pfizer-BioNTech) were identified after developing severe respiratory compromise post 2nd vaccine dose. Evaluation revealed AMR as the underlying etiology.ResultsAll patients were female, ages 50-70 years old, between 6 months and 2 years post-transplant. No previous rejection episodes. All were on standard IS as per institution protocols. Two were hospitalized with hypoxic respiratory failure within 2 weeks of their 2nd vaccine dose. The 3rd was seen at clinic for milder similar symptoms, later progressing and requiring supplemental oxygen (O2) and hospitalization. Imaging showed new lung infiltrates, infectious work up was negative. Biopsies did not show any cellular rejection. All developed new DSAs and received treatment for AMR with plasmapheresis, IVIg, and Rituximab. Two recovered their lung function and are off supplemental O2, the 3rd did not and is re-listed for transplant.ConclusionWhile LTR have a diminished response to SARS-CoV-2 vaccines making them more vulnerable to the disease, their immune system's response may not always be clear. We report three cases of patients developing severe AMR from new DSAs that appear to be triggered by the COVID-19 vaccine. This vaccine responses should be collected in a database where each case can be investigated to help better understand the mechanism behind them and hopefully identifying LTR at risk. This can then be used to modify vaccination strategies and aid in preventing adverse outcomes in this vulnerable group of patients.

The way they look: Phenotypic prototypicality shapes the perceived intergroup attitudes of in- and out-group members

Even when people hold little prejudice themselves, expectations about how members of other groups perceive them may negatively influence interracial relations. In four pre-registered experiments, each using a full intergroup design with Black and White participants, we show that people infer negative meta-attitudes from out-group members whose appearance is phenotypically prototypical, which in turn leads to less favorable orientations toward intergroup contact, independent of personal attitudes. In Experiment 1, Black Americans, but not White Americans, perceived that more phenotypically prototypical out-group members held less favorable meta-attitudes, and this explained less favorable contact orientations. In Experiment 2, this pattern emerged for both groups of participants and was particularly pronounced among individuals higher in stigma consciousness. Experiment 3 replicated Experiment 2 with representative samples and demonstrated that the effect of phenotypic prototypicality was more pronounced among participants reporting greater previous rejection by the out-group. With few exceptions, participants in the experiments also perceived phenotypically prototypical in-group members as having less positive meta-attitudes and participants showed less favorable contact orientations toward these in-group targets. An internal meta-analysis supported the robustness of the findings in the first three experiments. In Experiment 4, direct evidence for the causal effect of the mediator meta-attitudes on orientations toward contact with in- and out-group members was obtained. In all studies, effects held controlling for participants' general intergroup attitudes and experiences, demonstrating the unique role of meta-attitudes in shaping intergroup relations. We discuss our results in light of previous research, highlight social implications, and suggest future directions.

Has previous loan rejection scarred firms from applying for loans during Covid-19?

The concept of the ‘discouraged’ borrower is well documented. In this paper, we consider whether smaller firms in the UK who have been previously rejected for bank loans have been scarred by the experience so badly that even in the presence of two exceptionally generous Covid-19 loan guarantee schemes, they still refuse to make an application. Furthermore, we also consider what happens when they do. As banks have either zero or minimal loss exposure, do they still maintain their normal strict lending protocols or do they relax their standards to fulfil the governments’ objective of supporting struggling businesses through the crisis? Our findings show that 72% of previously rejected borrowers are reluctant to request loans. We find some evidence that previously scarred firms faced such severe liquidity problems that they relaxed their distrust of banks during the Covid-19 crisis. However, their share of the government-guaranteed loan portfolio was slightly lower suggesting that banks were treating each new loan application on its merits.Plain English SummaryThe Covid-19 crisis hit smaller businesses so hard that even previously rejected borrowers were forced to apply for loans to keep them afloat. Previous loan rejections have not discouraged small businesses in the UK in applying for Covid-19 government-guaranteed loans. Banks have used the loan guarantee schemes to continue to supply loans to small business during the pandemic. Our paper analyses the important phenomenon of borrower scarring and discouragement, when potential debtors are self-excluded from the lending market because they have previous rejections or expect a negative bank response. We consider around 45,000 UK small businesses from 2018 to 2020. On the demand side, we find that the economic shock for small businesses during the pandemic dissipates the scarring effect. Specifically, we find that micro and small businesses had the highest loan demand in the first two quarters of the pandemic (from March 2020). On the supply side, we show that scarred borrowers were not routed onto Covid-19 government-guaranteed loan schemes. These findings show the importance of government-backed lending schemes for small businesses during crisis period.

Malignancies in renal transplant recipients: A retrospective single-center descriptive study

The risk of malignancy development in kidney transplant recipients (KTRs) is 2-3 times higher than in the general population. This picture, which emerged with chronic immunosuppressive use, has become more prominent in recent years as the ongoing cause of death in this population. This study aims to determine the common features of KTRs with malignancy in follow-up under a single-center experience. Thus, it is to save time by correctly determining our focus points in patient follow-up.&#x0D; Methods. The files of 403 patients who underwent kidney transplantation between 2005 and 2020 in our hospital were reviewed retrospectively. The clinical findings at admission were age, gender, primary disease, use of cyclophosphamide before transplant, duration of dialysis, number of human leukocyte antigen mismatch, transplantation time, previous rejection, the existence of associated viral infections, comorbid diseases, used induction therapy, maintenance immunosuppressive therapy, allograft survival, recipient survival, malignancy development time after transplantation, serum creatinine, glomerular filtration rate (GFR) and presence of proteinuria and hematuria. Using these data, we retrospectively analyzed the incidence and types of malignancies in KTRs.&#x0D; Results. During the follow-up period, 22cancer cases have been developed. The median age of the patient was 60 years (IQR 45-64.3) and patients were mostly male (77.3%) The median follow-up period was 111.5 months (IQR76.3–128.3). The median duration of dialysis was 54 months (IQR 11.5-78). The etiology of primary kidney disease in most KTRs recipients was unknown. The percentage of patients with mismatch 3 and above 3 was 86.3%. While the majority of patients received anti-thymocyte globulin (86.4 %) as induction therapy, maintenance therapy was mostly tacrolimus + mycophenolate mofetil + prednisolone (86.4 %). The median time from transplantation to the initial malignancy was 17.5 months (IQR 5-61.3). The most common initial malignancy was skin cancer (22.7%), followed by renal cell carcinoma originating from the native kidney (18.2%).&#x0D; Conclusion. Renal transplantation is the most favorable renal replacement therapy. Malignancies are now among the important causes of death in KTRs and these patients have a higher risk of developing cancer than the general population. Therefore, screening for cancer at certain intervals, especially in long-term and elderly recipients after transplantation, will positively affect the survival of the patient and functional renal graft.

Survival Outcome and Prognostic Factors of Corneal Transplantation: A 15-Year Retrospective Cohort Study at King Chulalongkorn Memorial Hospital.

PurposeTo evaluate long-term survival outcomes and determine the prognostic factors of corneal transplantation performed at a tertiary referral hospital in Thailand.DesignA 15-year retrospective cohort study.Materials and MethodsOne corneal graft per patient was selected; graft failure was defined as graft opacity due to recurrent disease or endothelial cell dysfunction. Kaplan–Meier survival analysis was performed. Median time to failure was compared using the Log rank test. Prognostic factors were identified using the Cox proportional hazards model.ResultsWe enrolled 704 transplanted grafts. Surgical indications were optical (88.5%), therapeutic (10.2%), and tectonic (1.3%). The most common diagnoses were corneal opacity (25.3%), bullous keratopathy (15.8%), and regraft (14.8%). The overall survival rates at 1, 3, 5, and 10 years were 87.5%, 72.0%, 59.2%, and 41.7%, respectively. Univariate analysis identified age, primary diagnosis, graft size, pre-existing glaucoma, prior lens status, prior intraocular surgery, indication for surgery, donor endothelial cell density, and previous graft rejection as prognostic factors for graft failure. Multivariate analysis revealed three prognostic factors: primary diagnosis of perforation/peripheral ulceration/Mooren’s ulcer (hazard ratio [HR]=28.57; 95% confidence interval [CI], 6.32–129.16; P<0.001), active keratitis (HR=24.30; 95% CI, 5.88–100.43; P<0.001), regraft (HR=9.37; 95% CI, 2.27–38.66; P=0.002), and pseudophakic/aphakic bullous keratopathy (HR=7.97; 95% CI, 1.93–32.87; P=0.004); pre-existing glaucoma (HR=1.52; 95% CI, 1.13–2.04; P=0.006); and previous graft rejection (HR=1.95; 95% CI, 1.54–2.48; P<0.001).ConclusionOverall corneal graft survival rate was high in the first postoperative year and decreased after that. Primary diagnosis, pre-existing glaucoma, and previous graft rejection negatively influenced graft survival.