Cohort Of Recipients Research Articles

Immunosuppressive Therapy Modifies Anti-Spike IgG Subclasses Distribution After Four Doses of mRNA Vaccination in a Cohort of Kidney Transplant Recipients

Background: IgG4 is the least immunogenic subclass of IgG. Immunization with mRNA vaccines against SARS-CoV-2, unlike other vaccines, induces an increase in IgG4 against the spike protein in healthy populations. This study investigated whether immunosuppressive therapy affects the immune response, focusing on IgG subclass changes, to four doses of mRNA vaccine in kidney transplant recipients (KTRs). Methods: This study includes 146 KTRs and 23 dialysis patients (DPs) who received three mRNA-1273 vaccine doses and a BNT162b2 booster. We evaluated anti-spike IgG titers and subclasses, T-CD4+ and T-CD8+ cellular responses, and serum neutralizing activity (SNA). Results: At the fourth dose, 75.8% of COVID-19 naïve KTRs developed humoral and cellular responses (vs. 95.7% in DPs). There was a correlation between anti-spike IgG titers/subclasses and SNA (p < 0.001). IgG subclass kinetics after the third/fourth dose differed between COVID-19 naïve KTRs and DPs. Immunosuppressive therapy influenced IgG subclasses: mTOR inhibitors (mTORi) positively influenced IgG1 and IgG3 (p < 0.05), while mycophenolic acid negatively affected IgG1, IgG3, and IgG4 (p < 0.05). SNA is correlated with breakthrough infections after four doses of vaccine in KTRs. mTORi was the only factor associated with SNA > 65% in naïve KTRs [4.29 (1.21–15.17), p = 0.024]. Conclusions: KTRs show weaker cellular and humoral immune responses to mRNA vaccines and a class shift towards non-inflammatory anti-S IgG4 upon booster doses. IgG subclasses show a positive correlation with SNA and are influenced by immunosuppression. Increased SNA after four doses of vaccine is protective against infection. mTORi may benefit non-responding KTRs.

Cognitive dysfunction, psychiatric distress, and functional decline after liver transplantation

Impaired cognition in liver recipients has been studied in the immediate post-transplant period but is poorly understood long-term, despite its importance to quality of life. In a single-center cohort of liver recipients transplanted 2010-2022 and >1 years post-transplant, we assessed cognitive performance using a telephone-based battery. We compared depression, anxiety, and self-reported function by cognitive performance using descriptive statistics. Among 120 participants (median age 65, median 7.3 y post-transplant), 25% had below-expectation cognition, 53% at-expectation cognition, and 22% above-expectation. Baseline characteristics were similar between groups. Below-expectation performance was most commonly observed in verbal learning (28%) and verbal memory (22%). Overall, 46% had symptoms of depression (38%) and/or anxiety (28%); anxiety was less common among those with above-expectation cognition (0%) versus below-expectation (34%) or at-expectation cognition (38%, P=0.01). Impaired global daily function was reported by 36% of recipients but was not associated with objective cognitive performance. Below-expectation cognition was prevalent among 25% of liver recipients at least 1 year post-transplant and was associated with higher likelihood of reporting psychiatric distress. These findings underscore the need for longitudinal assessment of cognitive and mental health outcomes among liver transplant recipients.

Obesity and metabolic syndrome in a diverse pediatric kidney transplant population: which anthropometric measure best predicts arterial stiffness?

Obesity and metabolic syndrome (MS) accelerate arterial stiffening, increasing cardiovascular (CV) risk after transplant. BMI is limited by inability to differentiate muscle, fat mass, and fat distribution patterns. The aim of this study was to identify the best anthropometric measure to detect arterial stiffness as assessed by pulse wave velocity (PWV) in a racially diverse pediatric transplant population. Kidney transplant recipients 6-20years old and ≥ 6months post-transplant were prospectively enrolled. PWV was measured oscillometrically by Mobil-O-Graph. Skeletal muscle-to-fat mass ratio (SM:FM) and percent body fat (PBF) were evaluated by dual-frequency bioelectrical impedance. BMI and waist-to-height ratio (WHR) were calculated. Associations of arterial stiffness (high PWV) with obesity and MS as defined by WHR, SM:FM, PBF, and BMI were evaluated. Participants (n = 67) were 15 (IQR 11, 18) years old and 39 (IQR 10, 68) months post-transplant. Participants with SM:FM-obesity (OR 3.2) and WHR-obesity (OR 3.0) had increased odds of high PWV (p = 0.04) while PBF-obesity (OR 2.6, p = 0.09) and BMI-obesity (OR 2.2, p = 0.17) were not significant. Participants with WHR-MS (OR 12.5, p = 0.02), SM:FM-MS (OR 5.2, p = 0.03), and PBF-MS (OR 5.0, p = 0.02) had increased odds of arterial stiffness, while BMI-MS was not significant (OR 3.7, p = 0.08). Obesity is associated with arterial stiffness in a racially diverse cohort of pediatric transplant recipients. Anthropometric measures that assess body fat distribution (WHR) and body composition (SM:FM) are more strongly associated with arterial stiffness than BMI. MS has a stronger association with arterial stiffness than obesity alone, particularly when WHR is used.

Association between Everolimus Combination Therapy and Cancer Risk after Liver Transplantation: A Nationwide Population-based Quasi-Cohort Study.

The potential of everolimus in reducing hepatocellular carcinoma (HCC) among recipients following liver transplantation has been reported. This nationwide population-based quasi-cohort study investigated whether combining everolimus with calcineurin inhibitor therapy affects the risk of HCC and extrahepatic cancers compared to a time-duration-matched cohort of recipients not receiving everolimus. Using data covering the entire population from Korea, liver transplant recipients who had initiated immunosuppressants between June 2015 and February 2020 were collected and divided into two groups: the everolimus combination and non-combination groups. We calculated adjusted hazard ratios (aHRs) and absolute risk reduction (ARR) for the risk of HCC and extrahepatic cancer with everolimus combination therapy using a Cox regression model. A time-duration-matched retrospective cohort of 932 recipients in both of the groups was identified. The everolimus combination group showed a lower risk of HCC (aHR, 0.53; 95% confidence interval [CI] 0.30-0.94) and extrahepatic cancers (aHR, 0.30; 95% CI 0.14-0.63) compared to the non-combination group. The ARR was 0.004 for HCC and 0.012 for extrahepatic cancer. The findings suggest that adding everolimus to calcineurin inhibitor therapy reduces cancer risk in liver transplant recipients, highlighting the importance of considering cancer risk when choosing immunosuppressive therapies.

A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy

Immune checkpoint blockade (ICB) has become a standard anti-cancer treatment, offering durable clinical benefits. However, the limited response rate of ICB necessitates biomarkers to predict and modulate the efficacy of the therapy. The gut microbiome’s influence on ICB efficacy is of particular interest due to its modifiability through various interventions. However, gut microbiome biomarkers for ICB response have been inconsistent across different studies. Here, we identify TANB77, an uncultured and distinct bacterial clade, as the most consistent responder-enriched taxon through meta-analysis of ten independent ICB recipient cohorts. Traditional taxonomy fails to distinguish TANB77 from unrelated taxa, leading to its oversight. Mice with higher gut TANB77 abundance, either naturally or through transplantation, show improved response to anti-PD-1 therapy. Additionally, mice injected with TANB77-derived pilin-like protein exhibit improved anti-PD-1 therapy response, providing in vivo evidence for the beneficial role of the pilin-like protein. These findings suggest that pilins from the TANB77 order may enhance responses to ICB therapy across diverse cohorts of cancer patients.

"Effect of post-kidney transplant diabetes mellitus on long-term outcomes in a cohort of pediatric kidney transplant recipients from 2005 to 2022." Survival analysis.

Post-transplantation diabetes mellitus and carbohydrate intolerance (PTDM/iCHO) are complications following solid organ transplantation, which significantly increases the risk of graft loss and mortality. However, data concerning long-term outcomes in paediatric kidney transplant recipients with PTDM/iCHO are scarce. This study aimed to evaluate the risk of graft loss in paediatric kidney transplant recipients with PTDM or iCHO compared with non-PTDM/iCHO. The study cohort included patients aged <18 who underwent a kidney transplant in a transplant centre from 2005 to 2022. The primary outcome was graft survival loss; secondary outcomes were acute rejection, renal function and mortality. Cumulative incidence of graft loss and acute rejection was estimated, considering death a competing risk. Fine and Gray's proportional subdistribution hazard model was used to analyse the effect of PTDM/iCHO status on the event. Seventy-six paediatric kidney transplant recipients were included. The incidence of PTDM and iCHO was 6.6% and 9.2%, respectively. Patients with PTDM/iCHO had a significantly higher cumulative graft loss incidence than those without (34.4% vs 13.9% at 36 months, p<0.008). Multivariable analysis revealed a threefold increased risk of graft loss in patients with PTDM/iCHO (HRadjusted 3.33, 95% CI 1.19 to 9.30, p=0.022). PTDM/iCHO was associated with a higher incidence of acute rejection (33.3% vs 14.5% at 1 year, p=0.025). Patients with PTDM/iCHO also exhibited significantly worse eGFR at all time points compared with patients without PTDM/iCHO (p=0.036) CONCLUSION: Patients with PTDM and iCHO had a higher risk of graft loss and lower renal function in paediatric kidney transplant recipients. This justifies close monitoring of metabolic complications in these patients.

Validity of the Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) tool in a Dutch cohort of transplant recipients

AbstractBackgroundTo identify patients with high risk of skin cancer, risk prediction tools have been developed.ObjectivesExternal validation of the Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) in a Dutch cohort of solid organ transplant recipients (SOTR) and exploration of the possibility of incorporating additional risk factors to enhance its predictive performance.MethodsWe used data from the ongoing, prospective TransplantLines Biobank and Cohort Study of the University Medical Center Groningen (Groningen, The Netherlands). We conducted a survival analysis using Fine and Gray models to determine the subdistribution hazard ratios of the SUNTRAC risk factors and groups, Wolbers C index to assess its discriminative power, and cumulative incidences of skin cancer to assess its calibration. We applied the same methods for the incorporation of additional risk factors to the model.ResultsA total of 2099 patients were included with a median age at transplantation of 52.1 years (Interquartile range [IQR]: 40.6–60.1) and a median follow‐up time of 6.6 years (IQR: 3.4–12.5). In total 478 (22.8%) patients developed skin cancer. Basal cell carcinoma (53.3%) and cutaneous squamous cell carcinoma (42.9%) were most prevalent. The cumulative incidences of skin cancer per SUNTRAC risk group at 10 years were: low‐risk (1.8%), medium‐risk (12.9%), high‐risk (34.3%) and very high‐risk (68.6%). Significantly different skin cancer risk rates were observed for the medium‐risk (SHR = 9.9, 95% CI: 2.51–39.4), high‐risk (SHR = 21.5, 95% CI: 5.40–85.2) and very high‐risk (SHR = 80.3, 95% CI: 19.26–335.1) groups in reference to the low‐risk group. Wolbers C‐index at 5 years was 0.71. The model was well calibrated for our cohort. The addition of other potential risk factors yielded no or marginal improvement of discriminative value on top of SUNTRAC.ConclusionsSUNTRAC is valid for the general Dutch SOTR population, and it can be clinically implemented.

Biopsy-Proven T-Cell Mediated Rejection After Belatacept Rescue Conversion: A Multicenter Retrospective Study.

After kidney transplantation, conversion to belatacept is a promising alternative in patients with poor graft function or intolerance to calcineurin inhibitors. The risk of acute rejection has not been well described under these conditions. Here we present a retrospective multicenter study investigating the occurrence of acute rejection after conversion in 901 patients (2011-2021). The incidence of cellular and humoral rejection was 5.2% and 0.9%, respectively. T-cell mediated rejection (TCMR) occurred after a median of 2.6months after conversion. Out of 47 patients with TCMR, death-censored graft survival was 70.1%, 55.1% and 50.8% at 1year, 3years and 5years post-rejection, respectively. Eight patients died after rejection, mainly from infectious diseases. We compared these 47 patients with a cohort of kidney transplant recipients who were converted to belatacept between 2011 and 2017 and did not develop rejection (n = 238). In multivariate analysis, shorter time between KT and conversion, and the absence of anti-thymocyte globulin induction after KT were associated with the occurrence of TCMR after belatacept conversion. The occurrence of rejection after conversion to belatacept appeared to be less frequent than with de novo use. Nevertheless, the risk of graft loss could be significant in patients with already low renal function.

Evaluating the use of glucagon‐like peptide‐1 receptor agonists in a matched cohort of kidney and liver transplant recipients

AbstractBackgroundDiabetes mellitus (DM) and obesity are common among solid organ transplant recipients, but are associated with an increased risk of graft failure.AimAlthough glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are effective for managing both conditions in the general population, there is limited evidence regarding their use among transplant recipients.MethodThe effect of GLP‐1 RAs on post‐transplant glucose control (defined as haemoglobin A1c [HbA1c]) among 37 liver and kidney transplant patients was compared to a control cohort. Secondary outcomes included change in total daily insulin requirements and oral DM agents, estimated glomerular filtration rate (eGFR), weight, and body mass index (BMI). Adverse events attributed to GLP‐1 RAs, hypoglycaemia, incidence of pancreatitis, biopsy‐proven acute rejection, graft loss, and death were assessed. Ethical approval was granted by the Henry Ford Health Institutional Review Board (Reference no: 15959) and the study conforms with the US Federal Policy for the Protection of Human Subjects.ResultsWe observed that patients receiving GLP‐1 RAs had a median reduction in HbA1c of 0.5% and reduction in insulin and oral anti‐DM agents compared to the control group without GLP‐1 RAs. There were statistically significant reductions in both weight and BMI in the GLP‐1 RA group. Our observed incidence of adverse events was similar to previous literature. Unlike other smaller studies, a decline in eGFR was observed in the GLP‐1 RA group. There were no differences in incidence of biopsy‐proven acute rejection, graft loss, or death.ConclusionWhen compared to patients without GLP‐1 RA therapy, GLP‐1 RAs modestly reduced HbA1c and insulin requirements and statistically reduced weight/BMI review at 6 months. GLP‐1 RAs, even if initiated early post‐transplant, were seemingly safe and effective. Larger, prospective studies are warranted to evaluate the safety and efficacy of GLP‐1 RAs in this population.

The Relationship Between eSRTs and Upper Stimulation Levels in a Large Cohort of Adult Cochlear Implant Recipients.

To compare electrically evoked stapedial reflex thresholds (eSRTs) measured at 1 month post-activation to upper stimulation levels used for programming adult cochlear implant (CI) recipients over time in a large clinical population. Review of prospectively collected clinical database. Large CI program at an academic medical center. Postlingually deafened adult CI recipients (n = 439). eSRTs recorded in the medical record and upper stimulation levels derived from the programming software at 1 and 6 months post-activation. The correlation between eSRTs and upper stimulation levels was strong for all three manufacturers (r = 0.80-0.86). On average, upper stimulation levels were set 15.4 clinical levels below eSRT for Cochlear using a pulse width of 25 microseconds, 13.4 clinical levels below eSRT for Cochlear using a pulse width of 37 microseconds, 11.3 clinical units below eSRT for Advanced Bionics, and 0.1 charge unit above eSRT for MED-EL. eSRTs were found to be elicited at similar levels for different electrodes/frequencies across the array. After upper stimulation levels were set based on eSRT at 1 month post-activation, there was no significant change in upper stimulation levels between 1 and 6 months post-activation. eSRTs and upper stimulation levels are highly correlated. Average differences between eSRTs and upper stimulation levels reported herein can be used to guide programming in the clinic. Further, when eSRTs are used to program upper stimulation levels, upper stimulation levels should be relatively similar across channels and stable over time.

Clinical and Histopathological Findings in HIV-positive to HIV-positive Kidney Transplant Recipients.

The spectrum of histological findings in transplanted kidneys from HIV-positive donors to HIV-positive recipients is relatively unexplored. This study describes the type and timing of histological diagnoses observed in this unique cohort. Adequate biopsies were analyzed at implantation and posttransplant between September 2008 and May 2022. Histological disease spectrum, distributions over time, and relevant clinical characteristics and management were reported for both for-cause and protocol biopsies. Twenty-four implantation biopsies from 31 deceased donors and 179 allograft biopsies (100 for-cause, 79 protocol) from 50 recipients were analyzed. Most rejection episodes occurred in the first year posttransplant. Eighteen recipients (36%) had at least 1 episode of biopsy-confirmed acute/chronic T cell-mediated rejection (TCMR) or active antibody-mediated rejection (AMR). Protocol biopsies showed no active AMR or acute/chronic TCMR. However, 9 of 79 biopsies identified borderline/suspicious TCMR. Common nonrejection diagnoses were interstitial fibrosis and tubular atrophy, ascending pyelonephritis, and calcineurin inhibitor toxicity. Classic and suspected HIV-associated nephropathy (HIVAN) were identified in 3 and 6 patients, respectively. Protocol biopsies diagnosed 1 case of classic HIVAN and 6 cases of suspected HIVAN. AMR most adversely affected kidney function and significantly contributed to graft failure. The histological findings in this cohort of HIV-positive kidney transplant recipients who received grafts from unmatched HIV-positive donors revealed a spectrum of abnormalities. Protocol biopsies added to surveillance on borderline rejection and assisted in the recognition of HIVAN. Confirmed rejection occurred in 18 recipients (36%). Understanding the factors contributing to this may assist in the optimization of immunosuppressive protocols in the future.

Discordance between creatinine and cystatin C-based estimation of glomerular filtration rate (eGFR) in solid organ transplant recipients

BackgroundEstimation of glomerular filtration rate is a critical component of assessing kidney function post-solid organ transplantation and in monitoring risk of acute injury. Our objective was to evaluate estimated glomerular filtration rate (eGFR) as derived from creatinine (eGFRcr), cystatin C (eGFRcys), and both (eGFRcr-cys) in a cohort of transplant recipients. MethodsA total of 47 unique post-solid organ transplant patients receiving tacrolimus were included. Residual specimens were assayed for creatinine (Jaffe and enzymatic), cystatin C, and tacrolimus. eGFR was estimated using the 2021 CKD-EPI formulae. Results were compared by Deming regression and bias was assessed using non-parametric cumulative distribution plots. Percent agreement in chronic kidney disease (CKD) by stage was evaluated across equations. ResultseGFRcys relative to eGFRcr estimates demonstrated a median bias of –22 mL/min/1.73 m2 and an overall 21.3 % [95 % CI: 12.1, 35.0] agreement in CKD staging. eGFRcr-cys demonstrated a median bias of −14 mL/min/1.73 m2 and overall agreement of 34.0 % [95 % CI: 22.3, 48.4] relative to eGFRcr (enzymatic). Discordance increased proportionally with eGFR and did not differ by creatinine assay (Jaffe or enzymatic). ConclusionCystatin C incorporation leads to markedly negative biases between eGFR estimates in patients with solid organ transplant, implying lack of applicability of eGFRcys or GFRcr-cys in the transplant setting. This highlights the dependency of patient characteristics on equation performance and the need to consider confounding factors in interpretation and utilization of cystatin C based equations.

Abstract 4140138: Coronary Artery Vasculopathy in a Cohort of 321 Heart Transplant Recipients: A Single Center Experience

Introduction: Despite advances in surgical techniques, organ preservation methods and immunosuppressant medications, the ten-year survival for orthotropic heart transplantation (OHT) remains around 50%. Coronary artery vasculopathy (CAV), among other factors, seems to have an important role in accelerated organ injury and failure. Aim: To determine the rate of survival and CAV development along with associated factors in a cohort of OHT recipients. Methods: Patients who underwent OHT at Virginia Commonwealth University (VCU) between October 2008 and September 2021 were retrospectively reviewed until June 2024. According to the VCU protocol, right heart biopsies were done weekly for the first month, every other week for the second month and at the first year mark post transplant. Left heart catheterizations were done one year after OHT and then at 2 year intervals. Survival, CAV development and need for percutaneous coronary interventions (PCI) as well as organ rejection rates in CAV patients were surveyed. Results: A total of 321 patients received OHT during that period with a median follow up time of 8.15 years from the date of transplant. Of these, 122 patients had 10-year follow up or more post OHT (53.27% survived) and 240 patients had 5-year follow up or more (66.25% survived). All patients had greater than 2.75 years of follow up. The overall mortality was 29.5%. CAV occurred in 55 patients out of 321 (17%) with median time of 2.82 years for CAV development. Mortality in the CAV group was 40% compared to 27% in the non-CAV group. Out of 55 patients with CAV, 19 required at least 1 PCI with 3 requiring interventions on chronic total occlusions. Evidence of rejection on right ventricle biopsy was observed in 51% of patients with CAV Conclusion: Our cohort had above average 10-year survival rate compared to the national data. Results revealed CAV is common post OHT and has implications on long term survival. Given CAV may develop in the absence of organ rejection, further studies are needed to identify factors associated with CAV and explore optimal treatment options that would potentially improve long-term survival post OHT.

Prediction of Allograft Failure in Pediatric Kidney Transplant Recipients: A Validation Study of the Four-Variable Kidney Failure Risk Equation.

Recent findings suggest that the four-variable Kidney Failure Risk Equation (KFRE) may be useful in predicting the likelihood of allograft failure in adult kidney transplant (KT) recipients. However, research on its application in pediatric patients is lacking. This study aimed to assess the accuracy of the four-variable KFRE for prediction of the two-year and five-year risk of allograft failure in a cohort of pediatric KT recipients. A retrospective observational study of patients undergoing KT in a tertiary pediatric nephrology unit between 2007 and 2017 was conducted. The KFRE risk scores were determined using data collected one-year post-transplantation. Discrimination and calibration properties of the four-variable KFRE were assessed through the area under the receiver operating characteristic curves (AUC) and calibration plots. Fifty-nine patients with a median age of 12.4 (9.1-15.7) years at KT were included. Eleven (18.6%) were living donor recipients. The median estimated glomerular filtration rate one-year post-transplantation was 62.0 (49.0-75.0) mL/min/1.73 m2. One (1.7%) and three (5.1%) patients experienced allograft failure within two and five years following the one-year post-transplantation date, respectively. The four-variable KFRE showed excellent and very good discrimination for the two-year and five-year risks, respectively (AUC 0.966, 95% confidence interval (CI) 0.914-1.000; AUC 0.887, 95% CI 0.732-1.000). Calibration plots demonstrated imprecise calibration. The four-variable KFRE shows promise in predicting kidney failure progression in pediatric KT recipients with a functioning allograft one-year post-transplantation. Larger-scale studies are essential to confirm its predictive accuracy and establish more definitive conclusions.

Management of Post-transplant Infections in Collaborating Hospitals (MATCH) Programme: a prospective cohort of all transplant recipients at Copenhagen University Hospital—Rigshospitalet, Denmark

PurposeThe Management of Post-transplant Infections in Collaborating Hospitals (MATCH) programme, initiated in 2011 and still ongoing, was created to 1) optimise the implementation of existing preventive strategies against viral infections...

Burden of atherogenic lipids and association with cardiac allograft vasculopathy in heart transplant recipients,

BackgroundCardiac Allograft Vasculopathy (CAV) is a leading cause of morbidity and mortality after heart transplantation. There are limited contemporary studies examining post-transplant lipid management and cardiometabolic health. ObjectiveWe study the burden of cardiometabolic derangements post transplantation and its impact on CAV in a modern cohort of heart transplant recipients. MethodsAll heart transplant (HTx) recipients between January 2019 and December 2020, with two lipid assessments and angiographic surveillance were included. Logistic regression was used to assess association of lipid levels with cardiovascular outcomes and CAV. ResultsAmong 87 HTx recipients, atherogenic lipids were significantly elevated after Htx. Median LDL-C increased from a baseline level of 69.5 mg/dL to 86.5 mg/dL, p = 0.002, non-HDL-C 91.5 mg/dL to 118 mg/dL, p < 0.001, triglycerides 94.5 mg/dL to 133 mg/dL, p < 0.001, and remnant cholesterol 19 mg/dL to 27 mg/dL, p < 0.001. Increases in non-HDL-C, triglycerides, and remnant cholesterol were significantly associated with increased risk of CAV (Stanford Grade 4 and intimal thickness). Increases in triglycerides and remnant-C were associated with increased risk of composite major adverse cardiovascular events. ConclusionWe demonstrate a significant increase in atherogenic lipids two years following transplantation with low use (20 %) of high-intensity statin. Increase in atherogenic lipids was associated with increased risk of CAV and increase in triglycerides and remnant cholesterol with increased MACE. Future studies examining cardiometabolic consequences of heart transplantation and optimal treatment strategies to reduce risk of CAV and MACE are needed.

Effect of days of age at first blood transfusion on intraventricular hemorrhage in very low and extremely low birth weight infants

ABSTRACT Background Preterm infants are a group cohort of transfusion recipients due to their low blood volume and underdeveloped hematopoietic system. The objective of this study was to probe the effect of days of age at first blood transfusion on intraventricular hemorrhage (IVH) in very low and extremely low birth weight VLBW and ELBW infants. Research design and methods Data of 150 VLBW and ELBW infants receiving blood transfusions were reviewed. IVH and non-IVH groups were established. General data on infants and their mothers and data related to blood transfusion, IVH risk factors, and the predictive value of the relevant factors for IVH were analyzed. Results The IVH group had lower birth weight, hemoglobin levels on admission, and days of age at first blood transfusion and higher 5-min Apgar score ≤7 points and early transfusion rate. Spontaneous delivery and 5-min Apgar score ≤7 points were risk factors for IVH. Birth weight and days of age at first blood transfusion had predictive value for IVH in VLBW and ELBW infants. Conclusions The younger the days of age at first blood transfusion, the higher the IVH risk. It is necessary to delay the days of age at first blood transfusion and reduce early blood transfusion.

Timeline and outcomes of viral and fungal infections after Chimeric Antigen Receptor (CAR) T-cell therapy: A large database analysis

ObjectivesThis large database analysis aims to describe the incidence, timeline, and risk factors for viral and fungal infections after chimeric antigen receptor (CAR) T-cell therapy. MethodsWe queried a global research network database, TriNetX, for patients who received CAR T-cell therapy, who were identified and followed for the development of viral and fungal infections. Baseline demographic, oncologic history, laboratory data and medication histories were collected. We evaluated risk factors for respiratory viral infections (RVI), herpesvirus, fungal infections and mortality using Cox regression. ResultsA total of 2,256 patients who received CAR T-cell therapy were included, 1,867 (82.7%) were CD19-targeted and 400 (17.7%) were BCMA-targeted. Following CAR T-cell infusion, RVI were the most prevalent (23.3%) with a median onset of 160 days (IQR 52-348 days), while herpesvirus and fungal infections were less frequent, occurring in 13.6% and 11.4% of cases with median onsets of 71 (IQR 18-252) and 73 days (IQR 14-236 days), respectively. On multivariable Cox regression, independent predictors of RVI included acute lymphoblastic leukemia (ALL, HR 1.61), prior hematopoietic cell transplant (HCT, HR 1.29), cytokine release syndrome (CRS, HR 1.41), hemophagocytic lymphohistiocytosis (HLH, HR 1.96), and glucocorticoids (HR 3.37). Prior HCT (HR 2.00), hypogammaglobulinemia (HR 1.51), immune-effector cell-associated neurotoxicity syndrome (ICANS, HR 1.52), and HLH (HR 1.99) were associated with a higher risk of herpesviruses. Independent predictors of fungal infections included prior HCT (HR 1.59), CRS (HR 1.58) and hypogammaglobulinemia (HR 1.40). Idecabtagene vicleucel was associated with a lower risk of herpesvirus and fungal infections (HR 0.39 and 0.44, respectively). ConclusionsIn a large cohort of CAR T-cell therapy recipients, respiratory viral infections were the most common but occurred later, while herpesvirus and fungal infections were less frequent but occurred earlier. Prospective studies investigating prophylaxis and pre-emptive monitoring strategies are needed in this population.

Donor and Recipient Factors Associated with Primary Graft Dysfunction Following Lung Transplantation: A DMG Registry Analysis

Current risk-adjusted models to predict primary graft dysfunction (PGD) following lung transplantation (LTx) do not include bedside donor critical care data. Donor management goals (DMG) represent predefined critical care endpoints aimed at optimizing multi-organ donor management. Here, we sought to identify novel predictors to better understand the relationship between donor management and PGD following LTx. We used the national DMG registry to identify a cohort of LTx recipients linked to their respective donors between January 1st, 2015 and March 1st, 2023. Grade 3 PGD (PGD3) was defined according to modified ISHLT criteria. Multivariable modeling was performed to identify risk factors for the development of PGD3. A total of 2704 eligible patients were identified of which 643 (23.8%) developed PGD3. After multivariable modeling, the likelihood of PGD3 was greater with increased donor age (OR 1.06 [1.02, 1.10] per 5 year change, p=0.003), increased donor serum pH at the time of authorization (OR 1.14 [1.02, 1.25] per 0.1 increase, p=0.016), donor history of cocaine use (OR 1.34 [1.05, 1.71], p=0.020), and increased recipient central venous pressure (1.03 [1.01, 1.06], p=0.005). Recipients who received donor lungs in which the DMG for PF ratio was met had a lower likelihood of developing PGD3 (OR 0.63 [0.46, 0.86], p=0.006). This study leverages a novel detailed donor management database to identify factors associated with the development of PGD3. These factors may be used to recognize donors and recipients that may benefit from early interventions to improve short-term outcomes.

Risk stratification for a primary prevention ICD: Performance of the MADIT-ICD Benefit Score in contemporary real world patients

Abstract Background We have recently developed the MADIT-ICD Benefit Score to improve risk stratification for primary implantable cardioverter defibrillator (ICD) implantation by assessing the competing risk of life-threatening ventricular tachyarrhythmia (VTA) vs. non-arrhythmic mortality based using simple clinical variables. Patients with a MADIT-ICD Benefit Score of &amp;lt; 50 are more likely to experience non-arrhythmic mortality than life-threatening VTA, and therefore derive limited benefit from a prophylactic ICD. Purpose We aimed to provide data on the performance of the MADIT-ICD Benefit Score in a real world population, comprising patients with HFrEF and either ischemic or nonischemic cardiomyopathy (ICM/NICM) who are treated with contemporary guideline-directed medical therapy (GDMT). Methods The study population comprised 2875 patients who were implanted with a primary prevention ICD and prospectively followed in a large tertiary healthcare system (the University of Rochester Medical Center, including 3 affiliated hospitals in Upstate New York) between 2017 through 2023. Arrhythmic events were captured from device interrogation data, which were blindly adjudicated by 2 electrophysiologists. Results Among the 2875 study patients, mean age was 62 ± 15 years, 1265 (44%) were women, and 1667 (58%) had ICM. Guideline-directed medical therapies, including angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, angiotensin receptor/neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose transport protein 2 (SGLT2) inhibitors, were prescribed to 43%, 36%, 96%, 67% and 32% of study patients, respectively. The 2-year cumulative incidence of VTA, after accounting for the competing risk of death, was 19% vs. 11% in patients with a Score of ≥50 vs. &amp;lt;50, respectively (p&amp;lt;0.001; Figure 1A). Findings regarding ICD shocks were consistent (8% vs. 4%, respectively, p&amp;lt;0.001; Figure 1B) The rate of VTA events at 4 years was directly correlated with increasing quartiles of the MADIT-ICD Benefit Score, while the corresponding rates of non-arrhythmic mortality were inversely correlated with score quartiles (Figure 1C). A similar direct correlation with increasing Benefit Score quartiles was observed when the endpoint of ICD shocks was assessed (Figure 1D). Accordingly, the benefit of the ICD (calculated as the difference between predicted rates of VTA/shock events and corresponding rates of non-arrhythmic mortality) was attenuated with decreasing quartiles of the MADIT-ICD Benefit Score (Figures 1C and 1D; right column). Conclusions We show good performance of the MADIT-ICD Benefit Score in a large cohort of real world ICD recipients who are treated with contemporary GDMT. These data support the use of the MADIT-ICD Benefit Score for improved risk stratification and for shared decision-making in contemporary candidates for a primary prevention ICD.