Pulmonary transplantation-is it a long-term solution?
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ABSTRACT:
SUBMITTER: Kandasamy S
PROVIDER: S-EPMC10482618 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Publications
Pulmonary transplantation-is it a long-term solution?
Kandasamy Sivaveera S Lau Christine L CL Krupnick Alexander Sasha AS
Journal of thoracic disease 20230727 8
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Project description:Both early- and late-onset noninfectious pulmonary injury are important contributors to the nonrelapse mortality seen after allogeneic stem cell transplantation (allo-SCT), particularly in subjects conditioned with high-dose total body irradiation (TBI). To characterize the kinetics of recovery from pulmonary injury in long-term survivors, we collected data on 138 subjects who survived > 3 years (median survival, 10.2 years) after predominantly TBI-based allo-SCT from their HLA-matched siblings. Baseline pulmonary function tests served as the reference for subsequent measurements at 3, 5, 10, and 15 years for each survivor. The only parameter showing a clinically and statistically significant decline post-transplant was adjusted diffusion capacity of lung for carbon monoxide (DLCO), which reached a nadir at 5 years but surprisingly normalized at the 10-year mark. Multivariable modeling identified chronic graft-versus-host disease (P < .02) and abnormal baseline-adjusted DLCO (P < .03) as the only significant factors associated with the decline in adjusted DLCO at 5 years but excluded smoking, conditioning intensity, baseline C-reactive protein level, TBI dose to the lungs, disease, and demographic variables. In conclusion, pulmonary injury as monitored by the adjusted DLCO continues to deteriorate in the first 5 years after allo-SCT but recovers at 10 years.
| S-EPMC3918472 | biostudies-literature
Project description:Normothermic machine perfusion (NMP) has become a valuable tool to expand the pool of transplantable organs. However, the application of NMP to kidneys presents substantial challenges, mostly due to high variability in the configuration of perfusion buffers. Here we introduce a multimodal atlas of kidney cell injury associated with NMP using a literature-based consensus buffer. This resource provided the foundation for a systematic cross-species framework with integrated metabolic, genomic, spatial proteomic, and histopathologic profiling that was used to re-engineer the consensus perfusion buffer, mitigating cellular damage ex vivo and in vivo, thus extending organ viability and improving adequacy for transplantation.
2025-08-09 | GSE243729 | GEO
Project description:BackgroundSurvivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for pulmonary adverse events. Data on late-onset noninfectious pulmonary complications in long-term adult survivors of allo-HSCT are limited and incomplete.ObjectivesThis study aimed (1) to determine occurrence and degree of pulmonary sequelae in adult survivors of allo-HSCT and (2) to identify associations between pulmonary function, high-resolution CT (HRCT), and clinical characteristics.MethodIn a nationwide, single-center cross-sectional study, 103 survivors (aged median [range] 35 [17-58] years, 53% females) were examined 17 (6-32) years after allo-HSCT and compared with healthy controls (n = 105). Methods included pulmonary function tests and HRCT.ResultsChronic graft-versus-host disease was diagnosed in 33% of survivors, including 12% with bronchiolitis obliterans syndrome (BOS). Mean lung volumes (TLC, FVC, and FEV1) and gas diffusing capacity were >80% of predicted for the survivors as a group, but significantly lower than in healthy controls. Pathological HRCT findings were detected in 48% of the survivors (71% airways disease, 35% interstitial lung disease, and 24% apical subpleural interstitial thickening). Air trapping (%) on HRCT correlated with % predicted FEV1, p < 0.001. In a multiple logistic regression model, both BOS and pathological findings on HRCT were associated with chemotherapy prior to allo-HSCT, p < 0.05.ConclusionsLong-term allo-HSCT survivors had significantly lower pulmonary function than age- and gender-matched healthy controls and nearly half had pathological findings on HRCT. Longitudinal data will determine if pulmonary sequelae will remain stable or progress. We recommend lifelong monitoring of pulmonary function in allo-HSCT survivors. HRCT provides additional information, but is not suited for surveillance.
| S-EPMC9248297 | biostudies-literature
Project description:AimsWe compared hemodynamics and clinical events after heart transplantation (HTx) in patients stratified by the severity of residual pulmonary vascular resistance (PVR) after left ventricular assist device (LVAD) implantation for bridge to transplantation.MethodsWe retrospectively analyzed patients who had undergone HTx at the University of Tokyo Hospital. We defined the high PVR group as patients with PVR of >3 Wood Units (WU) as measured by right heart catheterization performed 1 month after LVAD implantation.ResultsWe included 85 consecutive HTx recipients, 20 of whom were classified in the high PVR group and 65 in the low PVR group. The difference in PVR between the two groups became apparent at 2 years after HTx (the high PVR group: 1.77 ± 0.41 WU, the low PVR group: 1.24 ± 0.59 WU, p = 0.0009). The differences in mean pulmonary artery pressure (mPAP), mean right arterial pressure (mRAP), and mean pulmonary capillary wedge pressure (mPCWP) tended to increase from the first year after HTx, and were all significantly higher in the high PVR group at 3 years after HTx (mPAP: 22.7 ± 9.0 mm Hg vs. 15.4 ± 4.3 mm Hg, p = 0.0009, mRAP: 7.2 ± 3.6 mm Hg vs. 4.1 ± 2.1 mm Hg, p = 0.0042, and mPCWP: 13.4 ± 4.5 mm Hg, 8.8 ± 3.3 mm Hg, p = 0.0040). In addition, pulmonary artery pulsatility index was significantly lower in the high PVR group than in the low PVR group at 3 years after HTx (2.51 ± 1.00 vs. 5.21 ± 3.23, p = 0.0033). The composite event including hospitalization for heart failure, diuretic use, and elevated intracardiac pressure (mRAP ≥ 12 mm Hg or mPCWP ≥ 18 mm Hg) between the two groups was significantly more common in the high PVR group. Residual high PVR was still an important predictor (hazard ratio 6.5, 95% confidence interval 2.0-21.6, and p = 0.0023) after multivariate Cox regression analysis.ConclusionOur study demonstrates that patients with residual high PVR under LVAD implantation showed the increase of right and left atrial pressure in the chronic phase after HTx.
| S-EPMC9198244 | biostudies-literature
Project description:BACKGROUND Kidney transplant recipients have higher life expectancy but may require subsequent transplantations, raising ethical concerns regarding organ allocation. We assessed the safety of multiple kidney transplants through long-term follow-up. MATERIAL AND METHODS A retrospective cohort study was conducted at a single center, categorizing patients based on the number of kidney transplantations received. The primary outcome was the composite of death-censored graft failure and overall mortality. The secondary outcome was death-censored graft failure. RESULTS Between 2000 and 2019, our center performed 2152 kidney transplantations. Patients were divided into 3 groups: A (1 transplant; n=1850), B (2 transplants; n=285), and C (3 or more transplants; n=75). Group C patients were younger, had fewer comorbidities, and received more aggressive induction therapy. The primary outcomes, including death-censored graft loss and overall mortality, showed similar rates across groups (A: 21.3%, B: 25.2%, C: 21.7%, p=0.068). However, the secondary outcome of death-censored graft failure alone was significantly lower in group A compared to the other groups. No significant difference was observed between groups B and C (8% vs 16% and 13%, respectively, p=0.001, p=0.845). Multivariate analysis identified having a living donor as the strongest predictor of patient and graft survival in all study groups. CONCLUSIONS Graft and patient survival rates were similar between first and multiple transplant recipients. Multiple transplant recipients had lower death-censored graft failure risk compared to first transplant recipients. However, the risk did not differ among second and subsequent transplant recipients. Younger patients, especially those with a living donor, should be considered for repeat kidney transplantation.
| S-EPMC11299480 | biostudies-literature
Project description:BACKGROUND:Fecal microbiota transplantation (FMT) has been recently approved by FDA for the treatment of refractory recurrent clostridial colitis (rCDI). Success of FTM in treatment of rCDI led to a number of studies investigating the effectiveness of its application in the other gastrointestinal diseases. However, in the majority of studies the effects of FMT were evaluated on the patients with initially altered microbiota. The aim of our study was to estimate effects of FMT on the gut microbiota composition in healthy volunteers and to monitor its long-term outcomes. RESULTS:We have performed a combined analysis of three healthy volunteers before and after capsule FMT by evaluating their general condition, adverse clinical effects, changes of basic laboratory parameters, and several immune markers. Intestinal microbiota samples were evaluated by 16S rRNA gene and shotgun sequencing. The data analysis demonstrated profound shift towards the donor microbiota taxonomic composition in all volunteers. Following FMT, all the volunteers exhibited gut colonization with donor gut bacteria and persistence of this effect for almost ∼1 year of observation. Transient changes of immune parameters were consistent with suppression of T-cell cytotoxicity. FMT was well tolerated with mild gastrointestinal adverse events, however, one volunteer developed a systemic inflammatory response syndrome. CONCLUSIONS:The FMT leads to significant long-term changes of the gut microbiota in healthy volunteers with the shift towards donor microbiota composition and represents a relatively safe procedure to the recipients without long-term adverse events.
| S-EPMC6938016 | biostudies-literature
Project description: Not available
| S-EPMC10586948 | biostudies-literature
Project description:Encapsulation of therapeutic cells in a semipermeable device can mitigate the need for systemic immune suppression following cell transplantation by providing local immunoprotection while being permeable to nutrients, oxygen, and different cell-secreted biomolecules. However, fibrotic tissue deposition around the device has been shown to compromise the long-term function of the transplanted cells. Herein, a macroencapsulation device design that improves long-term survival and function of the transplanted cells is reported. The device is comprised of a semipermeable chitosan pouch with a tunable reservoir and molecularly engineered interface. The chitosan pouch interface decorated with 1,12-dodecanedioic acid (DDA), limits the cell adhesion and vigorous foreign body response while maintaining the barrier properties amenable to cell encapsulation. The device provides long-term protection to the encapsulated human primary hepatocytes in the subcutaneous space of immunocompetent mice. The device supports the encapsulated cells for up to 6 months as evident from cell viability and presence of human specific albumin in circulation. Solutions that integrate biomaterials and interfacial engineering such as the one described here may advance development of easy-to manufacture and retrievable devices for the transplantation of therapeutic cells in the absence of immunosuppression.
| S-EPMC10622113 | biostudies-literature
Project description:BackgroundThe definitive treatment for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA), which has good long-term outcomes. However, after surgery, a quarter of the patients still have residual pulmonary hypertension (RPH). In pulmonary hemodynamics, there are no unified criteria for RPH, even though the level may affect long-term survival.MethodsBetween March 1997 and December 2021, 253 CTEPH patients were treated at our center with PEA. Patients were evaluated retrospectively and classified into early (1997-2014) and late (2015-2021) groups. The clinical characteristics and perioperative outcomes of the two groups were compared, and risk factor analysis for RPH and long-term survival for all cases was performed.ResultsThere was no statistically significant difference in demographics between the two groups. However, the Early Group had a significantly higher rate of perioperative death (9.8% vs. 1.2%, p = .001), RPH (48.8% vs. 14.0%, p < .001), and reperfusion pulmonary edema (18.3% vs. 2.9%, p < .001). The median follow-up time was 66.0 months, and overall survival rates at 5, 10, 15, and 18 years after PEA were 91.2%, 83.9%, 64.5%, and 46.0%, respectively. Age and postoperative systolic pulmonary artery pressure (sPAP) were independently related to long-term outcomes in the multivariate Cox analyses. Patients with postoperative sPAP less than 46 mm Hg had a higher chance of survival.ConclusionsPEA improved CTEPH hemodynamics immediately and had a positive effect on long-term survival. Patients with postoperative sPAP ≥ 46 mm Hg indicate clinically significant RPH and have a lower long-term survival rate.
| S-EPMC9748755 | biostudies-literature
Project description:Biomarkers are fundamental to basic and clinical research outcomes by reporting host responses and providing insight into disease pathophysiology. Measuring biomarkers with research-use ELISA kits is universal, yet lack of kit standardization and unexpected lot-to-lot variability presents analytic challenges for long-term projects. During an ongoing two-year project measuring plasma biomarkers in cancer patients, control concentrations for one biomarker (PF) decreased significantly after changes in ELISA kit lots. A comprehensive operations review pointed to standard curve shifts with the new kits, an analytic variable that jeopardized data already collected on hundreds of patient samples. After excluding other reasonable contributors to data variability, a computational solution was developed to provide a uniform platform for data analysis across multiple ELISA kit lots. The solution (ELISAtools) was developed within open-access R software in which variability between kits is treated as a batch effect. A defined best-fit Reference standard curve is modelled, a unique Shift factor "S" is calculated for every standard curve and data adjusted accordingly. The averaged S factors for PF ELISA kit lots #1-5 ranged from -0.086 to 0.735, and reduced control inter-assay variability from 62.4% to <9%, within quality control limits. S factors calculated for four other biomarkers provided a quantitative metric to monitor ELISAs over the 10 month study period for quality control purposes. Reproducible biomarker measurements are essential, particularly for long-term projects with valuable patient samples. Use of research-use ELISA kits is ubiquitous and judicious use of this computational solution maximizes biomarker reproducibility.
| S-EPMC6469750 | biostudies-literature