Ideal Donor Research Articles

Allogeneic Hematopoietic Stem Cell Transplantation in Thirty-Four Pediatric Cases of Mucopolysaccharidosis—A Ten-Year Report from the China Children Transplant Group

We investigated the efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in pediatric patients with mucopolysaccharidosis (MPS). A retrospective analysis of transplantation data from 34 cases of MPS from the China Children Transplant Group, treated between December 2004 and September 2015, was conducted. Among the 34 cases, 12 cases were type I, 12 were type II, 4 were type IV, 4 were type VI, and 2 were of an unknown type. The median age at transplantation was 3.75 years (range, 1 to 7 years); the median follow-up time was 14 months (range, 2 to 119 months). Eleven patients underwent unrelated cord blood transplantation and 23 underwent peripheral blood stem cell transplantation (4 cases with an HLA-matched sibling donor, 2 cases with an HLA-mismatched related donor, and 17 cases with an unrelated donor). A busulfan-based myeloablative regimen was used as a conditioning regimen. The estimated overall survival at 3 years was 84.8% ± 6.3% and 91.2% of the patients (31 of 34) achieved full donor chimerism. Twenty-seven children were evaluable and all but 1 (carrier sibling donor; enzyme level improved but failed to reach normal) achieved normal enzyme level after transplantation. The incidence of grades II to IV acute graft-versus-host disease (aGVHD) was 41.1% (14 of 34), wherein the incidence of grades III and IV aGVHD was 11.8% (4 of 34). The incidence of moderate-to-severe chronic graft-versus-host disease was 5.9% (2 of 34). There was a significant difference in the survival rate between children who received transplantation before 2009 and those after 2009 (55.6% versus 95.7%, P = .002); the survival rate was lower in patients with pneumonia before transplantation than in those with no active infection before transplantation (66.7% versus 95.5%, P = .019), and no significant differences in survival rates were observed among children with different disease types, ages at transplantation, donor/graft source, and conditioning regimens. After transplantation, upper-airway obstruction, hepatosplenomegaly, and corneal clouding were significantly improved; hearing and motor function were improved to a certain extent; valvular heart disease was improved in some patients but progressed in others; and short stature and speech skills showed little improvement. AlloHSCT may save the lives of patients with MPS I, II, IV or VI and could improve quality of life. Pretransplantation pneumonia affects transplantation outcomes. Advances in transplantation protocols and techniques help to improve patient prognosis. Well-matched unrelated donors can also be an ideal donor source. Standardized follow-up and a multidisciplinary team contribute to accurate evaluation of long-term post-transplantation outcome and further improve the quality of life of MPS patients.

Precision in donor selection: Identifying ideal stem-cell donors through their Tcells.

HLA-identical siblings have always been considered ideal donors for allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the treatment of hematologic cancers. Recent data suggest that we should rethink this paradigm. In "High Graft CD8+ Cell Dose Predicts Improved Survival and Enables Better Donor Selection in Allogeneic Stem-Cell Transplantation With Reduced-Intensity Conditioning," we identified a group of stem-cell donors whose grafts contain an optimal composition of T-cells, leading to a dramatic decrease in disease relapse risk and an improvement in overall survival following allo-HSCT. To demonstrate this, we analyzed the outcomes of 200 patients with hematologic malignancies who underwent allo-HSCT after reduced-intensity conditioning (RIC). The analysis focused on T-cell content of peripheral blood stem-cell grafts. We found that higher graft CD8+ T-cell dose (CD8hi), a trait found only in grafts collected from young donors, was associated with improved survival due to a reduction in the risk for cancer relapse without a significant increase in graft-versus-host disease (GVHD). Though not all young donors mobilized CD8hi grafts, we found that a low CD4:CD8 ratio in the peripheral blood could identify these ideal donors prior to transplant. The likelihood of finding CD8hi donors correlated inversely with age, and elderly RIC transplant recipients had a low chance of receiving an ideal graft from their similarly aged siblings. Here, we examine these findings and their implications on choosing donors according to age and relatedness. We also explore biological mechanisms that determine the CD4:CD8 ratio in healthy donors.

Prevalence of naturally occurring antibodies against dog erythrocyte antigen 7 in a population of dog erythrocyte antigen 7–negative dogs from Spain and Italy

OBJECTIVE To determine the prevalence of naturally occurring anti-dog erythrocyte antigen (DEA) 7 antibodies in DEA 7-negative dogs from Spain and Italy. ANIMALS 252 DEA 7-negative dogs from a population of 312 dogs that were previously tested for DEA 1, DEA 4, and DEA 7. PROCEDURES A plasma sample was obtained from each dog and evaluated for anti-DEA 7 antibodies by the use of gel column agglutination. Each plasma sample underwent major crossmatching with RBCs from DEA 7-positive dogs. Samples that resulted in agglutination were then crossmatched with RBCs from DEA 1-negative, DEA 4-positive, and DEA 7-negative dogs to confirm the presence of anti-DEA 7 antibodies. Results were then used to calculate the risk for a delayed transfusion reaction in a DEA 7-negative dog with anti-DEA 7 antibodies after a transfusion with blood that was not crossmatched or typed for DEA 7. RESULTS 96 of 252 (38.1%) plasma samples contained anti-DEA 7 antibodies. A DEA 7-negative dog with anti-DEA 7 antibodies had a 5.9% chance of developing a delayed hemolytic reaction after transfusion with blood not crossmatched or typed for DEA 7. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that canine blood used for transfusion should be crossmatched with the blood or plasma of the intended recipient prior to transfusion to minimize the likelihood that the recipient will develop a hemolytic reaction associated with anti-DEA 7 antibodies. Ideal canine blood donors should be negative for both DEA 1 and DEA 7.

Expanded Cheek-Shaped Flap for Aesthetic Cheek Reconstruction in the Cervicoperiauricular Area.

The cervical area is well acknowledged as an ideal donor site for aesthetic reconstruction of the cheek, and tissue expansion may play an important role for maximally achieving such a purpose. However, the conventional design of the expanded cervical flap generally results in unsightly morbidity of the donor site. The aim of this study is to evaluate the results of using an improvised cervical expanded flap in aesthetic reconstruction of the cheek. From July 2004 to October 2012, a total of 23 burn sequelae patients (30 cheeks) underwent cheek reconstruction with an expanded flap that originated from the cervicoperiauricular area. The procedures were initially carried out with the insertion of a round tissue expander in the cervicoperiauricular area, followed by serial inflation of the expander, and finally, transplantation of the expanded flap to the cheek in a rotation advancement fashion. The donor site closure was along the auricular sulcus. The average area of the harvested flaps was 9.7 × 8.1 cm. All the flaps completely survived, only one major complication occur-a dome exposure of the tissue expander after the expansion was completed. The flap was salvaged, and the transfer stage was done without intact. Minor complications after flap transfer include: widened scar at the donor site, a "dog-ear" needing additional minor surgery, distal part of the flap transient congestion. The patients achieved very satisfactory results functionally and aesthetically. Using the expanded cheek-shaped flap technique can provide a safe, thin, and color-matched flap in aesthetic reconstruction of the cheek with minimal donor site morbidity.

Controlled release hydrogen sulfide delivery system based on mesoporous silica nanoparticles protects graft endothelium from ischemia–reperfusion injury

Hydrogen sulfide (H2S) functions as a protective gas transmitter in various physiological and pathological processes, but the lack of ideal donors severely hampers the clinical application of H2S. This study aims to construct a controlled release H2S donor and evaluate its protective effect on graft endothelium. Mesoporous silica nanoparticles (MSNs) were synthesized using the sol–gel method and loaded with diallyl trisulfide (DATS), an H2S-releasing agent named DATS-MSN. In vitro experiments showed that DATS-MSN could alleviate endothelial cell inflammation and enhance endothelial cell proliferation and migration. In vivo experiments demonstrated that the apoptosis of graft endothelium was mitigated in the presence of DATS-MSN. Our results indicated that DATS-MSN, releasing H2S in a controlled release fashion, could serve as an ideal H2S donor.

Double forehead flap reconstruction of composite nasal defects

Composite nasal defects require skin, framework, and lining reconstruction. The forehead flap is an ideal donor for skin coverage because of good color match and excellent donor-site healing. Intranasal flaps and grafts are reserved for lining reconstruction of small defects. Locoregional and free flaps are used for larger lining defects, but these may not be ideal or safe. The authors advocate the double forehead flap for large composite defects of the nose in a subset of patients. Three men and three women aged 55-87 years (average 74.7 years) were treated for composite nasal defects that resulted from cancer (n=5) and trauma (n=1). Skin and lining defects were >2cm in every dimension. Double forehead flaps were raised in stages (n=1) or simultaneously (n=5), and nasal reconstruction was performed in two (n=1) or three stages (n=5). Patients were followed for 19.3 months (range 13-24 months). Donor sites of flaps raised in stages healed after 3 months. When flaps were raised together, healing required 5-13 months (average 7.6 months). There were no partial or complete flap losses. None of the patients had infection, hematoma, or nerve injury. Satisfactory aesthetic results were achieved in every case. The authors advocate the double forehead flap for large composite nasal defects in patients who are not suitable candidates for nasolabial flaps and those who may not tolerate free tissue transfer. The advantages of this method must be weighed against the drawbacks, which include prolonged donor-site healing and elimination of the contralateral forehead flap.

Boronate Affinity Fluorescent Nanoparticles for Förster Resonance Energy Transfer Inhibition Assay of cis-Diol Biomolecules.

Förster resonance energy transfer (FRET) has been essential for many applications, in which an appropriate donor-acceptor pair is the key. Traditional dye-to-dye combinations remain the working horses but are rather nonspecifically susceptive to environmental factors (such as ionic strength, pH, oxygen, etc.). Besides, to obtain desired selectivity, functionalization of the donor or acceptor is essential but usually tedious. Herein, we present fluorescent poly(m-aminophenylboronic acid) nanoparticles (poly(mAPBA) NPs) synthesized via a simple procedure and demonstrate a FRET scheme with suppressed environmental effects for the selective sensing of cis-diol biomolecules. The NPs exhibited stable fluorescence properties, resistance to environmental factors, and a Förster distance comparable size, making them ideal donor for FRET applications. By using poly(mAPBA) NPs and adenosine 5'-monophosphate modified graphene oxide (AMP-GO) as a donor and an acceptor, respectively, an environmental effects-suppressed boronate affinity-mediated FRET system was established. The fluorescence of poly(mAPBA) NPs was quenched by AMP-GO while it was restored when a competing cis-diol compounds was present. The FRET system exhibited excellent selectivity and improved sensitivity toward cis-diol compounds. Quantitative inhibition assay of glucose in human serum was demonstrated. As many cis-diol compounds such as sugars and glycoproteins are biologically and clinically significant, the FRET scheme presented herein could find more promising applications.

N-Heterocylic Carbene-Based Mn Electrocatalyst for Two-Electron CO2 Reduction over Proton Reduction

A bifunctional, chelating N-heterocyclic carbene-pyridine (NHC-pyridine) containing Mn(I) complex [MnBr(NHC-pyridine)(CO)3] displays a strong selectivity for CO2 reduction over proton reduction. Interestingly, the two-electron reduction of this complex occurs at a single potential, as opposed to MnBr(bpy)(CO)3, which is reduced by two electrons in two separate one-electron reductions. Here, the Gibbs free energy barriers, reduction potentials, rate constants, and pKa values are predicted with theory to understand the one- vs two-electron reduction mechanism. The effects of weak and strong Bronsted acids [HCl, TFE (2,2,2-trifluoroethanol), PhOH, CH3OH, and H2O] are studied to gauge the preference for CO2 vs proton reduction; water is found to be an ideal proton donor that allows for strong CO2 selectivity.

Comparison of Aerobic Preservation by Venous Systemic Oxygen Persufflation or Oxygenated Machine Perfusion of Warm-Ischemia-Damaged Porcine Kidneys

Background/Aim: The global shortage of donor organs for transplantation has necessitated the expansion of the organ pool through increased use of organs from less ideal donors. Venous systemic oxygen persufflation (VSOP) and oxygenated machine perfusion (OMP) have previously demonstrated beneficial results compared to cold storage (CS) in the preservation of warm-ischemia-damaged kidney grafts. The aim of this study was to compare the efficacy of VSOP and OMP for the preservation of warm-ischemia-damaged porcine kidneys using the recently introduced Ecosol preservation solution compared to CS using Ecosol or histidine-tryptophan-ketoglutarate solution (HTK). Materials and Methods: Kidneys from German Landrace pigs (n = 5/group) were retrieved and washed out with either Ecosol or HTK after 45 min of clamping of the renal pedicle. As controls, kidneys without warm ischemia, cold stored for 24 h in HTK, were employed. Following 24 h of preservation by VSOP, OMP, CS-Ecosol, or CS-HTK, renal function and damage were assessed during 1 h using the isolated perfused porcine kidney model. Results: During reperfusion, urine production was significantly higher in the VSOP and OMP groups than in the CS-HTK group; however, only VSOP could demonstrate lower urine protein concentrations and fractional excretion of sodium, which did not differ from the non-warm-ischemia-damaged control group. VSOP, CS-Ecosol, and controls showed better maintenance of the acid-base balance than CS-HTK. Reduced lipid peroxidation, as reflected in postreperfusion tissue thiobarbituric acid-reactive substance levels, was observed in the VSOP group compared to the OMP group, and the VSOP and CS-Ecosol groups had concentrations similar to the controls. The ratio of reduced to oxidized glutathione was higher in the VSOP, OMP, and CS-Ecosol groups than in the CS-HTK group and controls, with a higher ratio in the VSOP than in the OMP group. Conclusion: VSOP was associated with mitigation of oxidative stress in comparison to OMP and CS. Preservation of warm-ischemia-damaged porcine kidneys by VSOP was improved compared to OMP and CS, and was comparable to preservation of non-warm-ischemia-damaged cold-stored kidneys.

A Fluorinated Polythiophene Derivative with Stabilized Backbone Conformation for Highly Efficient Fullerene and Non-Fullerene Polymer Solar Cells

Here, taking a polythiophene derivative (PBDD4T) as a starting polymer, we tried to increase the rotation barrier and hence stabilize its backbone conformation by introducing fluorine into the β- and β′-position of the α-linked bithiophene segments and then synthesized a new polymer named as PBDD4T-2F. Our results demonstrate that the rotation barrier between the α-linked bithiophene significantly increases after the fluorination, so PBDD4T-2F has a more stable backbone conformation than PBDD4T. Compared to PBDD4T, PBDD4T-2F shows stronger aggregation effect in solution state and more compact π–π stacking in solid thin film and also possesses deeper HOMO level. These properties make PBDD4T-2F being an ideal donor material in PSCs. When blended with PC71BM, a fullerene acceptor, the PBDD4T-2F-based device showed a power conversion efficiency (PCE) of 9.04%, which is 38% higher than that of the PBDD4T-based device; when blended with ITIC, a non-fullerene acceptor, the PBDD4T-2F-based device showed a PCE of ...

Robotic Harvest of a Right Gastroepiploic Lymph Node Flap.

Lymph node flap (LNF) transfer has proven to be an effective option in the treatment of lymphedema. As a result, much research is presently focused on finding an ideal donor site that results in good clinical outcomes while avoiding iatrogenic lymphedema of the donor area.

Genetic analysis of attenuation markers of cold-adapted X-31 influenza live vaccine donor strain

Cold-adapted live attenuated influenza vaccines (CAIVs) have been considered as a safe prophylactic measure to prevent influenza virus infections. The safety of a CAIV depends largely on genetic markers that confer specific attenuation phenotypes. Previous studies with other CAIVs reported that polymerase genes were primarily responsible for the attenuation. Here, we analyzed the genetic mutations and their phenotypic contribution in the X-31 ca strain, a recently developed alternative CAIV donor strain. During the cold-adaptation of its parental X-31 virus, various numbers of sequence changes were accumulated in all six internal genes. Phenotypic analysis with single-gene and multiple-gene reassortant viruses suggests that NP gene makes the largest contribution to the cold-adapted (ca) and temperature-sensitive (ts) characters, while the remaining other internal genes also impart attenuation characters with varying degrees. A balanced contribution of all internal genes to the attenuation suggests that X-31 ca could serve as an ideal master donor strain for CAIVs preventing influenza epidemics and pandemics.

Banff score changes in kidneys from marginal donors

Despite an increase in the number of cadaver donors and the number of overall organ transplantations, the dramatic increase in the waiting list makes it necessary to reconsider donor criteria. The authors examined whether differences could exist in the function and/or morphology of transplanted kidneys originated from marginal and ideal donors one and five years after transplantation. Kidney function and histopathologic findings were analysed and compared one and 5 years after transplantation in 97 patients having marginal donor kidneys and 178 patients who received ideal donor kidneys. Serum creatinine level was significantly higher (p = 0.0001) and estimated glomerular filtration rate was significantly lower (p = 0.003) in patients having marginal donor kidneys as compared to those with ideal donor kidneys 5 years after transplantation. Morphological changes in the transplanted kidneys such as tubulitis (p = 0.014) and interstitial inflammation (p = 0.025) were significantly more frequently present in patients with marginal donor kidneys than in those with ideal donor kidneys one year after transplantation. Despite an absence of differences in kidney function one year after kidney transplantation between patients having marginal and ideal donor kidneys, morphologic differences in the transplanted kidneys can be detected between the two groups of patients.

Increased Disease Progression in HLA-a, -B, -C, -DRB1 and -DBP1 Matched Recipients of Unrelated Donor Transplants with Peripheral Blood Is Independent of Risk Groups By Disease Risk Index

The use of unrelated donors matched in all alleles of HLA-A, -B, -C, and -DRB1 loci has been associated with superior outcomes compared with those having 1 or more mismatches. Recent studies showed increased transplant-related mortality (TRM) with the use of HLA-DPB1 mismatched donors supporting the notion that the ideal volunteer unrelated donor should fully match at HLA-A, -B, -C, and -DRB1 and lack -DPB1 mismatches. The issue of the effect of HLA-DPB1 mismatch on the disease progression rate is still controversial and we aimed to investigate the impact of HLA-DPB1 mismatch in the graft versus host direction on transplant outcomes in patients categorized according to the recently defined disease risk index (DRI) for disease risk classification.Our study cohort included 1,211 transplant patients with hematological malignancies whohave received an hematopoietic stem cell transplant (HSCT) from an unrelated HLA-A, -B, -C,-DRB1 matched donor by high resolution typing (8/8 matched) after 2005 through 2014. The study cohort had a median age of 55 (range, 19-77); the hematopoietic stem cell source was peripheral blood (PB) in 698 and bone marrow (BM) in 513 patients. Disease risk index (DRI) at HSCT was high or very high in 382 (33%), intermediate in 598 (51%), low in 185 (16%) patients.Of the pairs, 1,154 (95%) were matched atHLA-DQB1 and 1,116 (92%) at HLA- DRB3/4/5 by high resolution testing. However, 633 (52%) had mismatch at one of the DPB1 alleles and 208 (17%) had two mismatches. There was association between matching for DPB1and matching for DRB3/4/5 (p=0.002) but not with DQB1.In PB recipients, there was a highly significant decreaseof disease progression in DPB1 mismatched pairs (one and two allele; HR=0.7, p=0.01 and HR=0.6, p=0.01 respectively) as compared tothose pairs with DPB1 matched. The impact of mismatches at one or two alleles were not different on disease progression (HR=1.2, p=0.4). However, the impact of DPB1 mismatch on disease progression was not uniform in different disease risk groups by DRI. Mismatch at DPB1 significantly decreased disease progression only in the intermediate risk group (HR=0.5, p=0.002) but not in low risk and high/very high disease groups by DRI (HR=0.9, p=0.8 and HR=0.7, p=0.1 respectively) (Figure 1a-c).In BM recipients, increasing number of DPB1 incompatibilities decreased disease progression (HR=0.9, p=0.4 and HR=0.6, p=0.1 for 1 and 2 allele mismatches respectively) but did not reach significance. Mismatches at HLA-DQB1 and -DRB3/4/5 had no impact on disease progression in both PB and BM recipients.Pairs with one or two allele-level DPB1 mismatches increased TRM compared with DPB1 matched pairs in PB (HR=1.5, p=0.04 and HR=1.9, p=0.006 respectively) and BM recipients (HR=1.8, p=0.03 and HR=1.9, p=0.05). There was no difference between two and one allele DPB1 mismatched for TRM in PB and BM recipients. Multivariate analyses revealed that the negative impact of DPB1 mismatch on TRM was not uniform in younger or (?) older patients. Interestingly, DPB1 mismatches increased TRM only in younger (aged<55) patients (HR=2.3, p=0.02) if they were PB recipients but only in older patients (HR=2.03, p=0.046) if they were BM recipients.We next analyzed the impact of DPB1 matching on progression free survival (PFS) and did not observe any impact of DPB1 mismatches on PFS in PB (HR=0.9, p=0.9) and BM (HR=1.12, p=0.6) recipients. Subgroup analyses by DRI to identify a specific risk group that the use of HLA-A, -B, -C and -DRB1 matched but DPB1 mismatched unrelated donor might lead to improved PFS did not reveal any particular risk group in both PB and BM recipients.Thus, in recipients of HLA-A, -B-C and DRB1 allele-level matched unrelated donors a mismatch for DPB1 is associated with a significantlydecreased risk of disease progression with no impact on PFS in intermediate risk group by DRI. Further analysis permissive vs. non-permissive DPB1 mismatches would be warranted. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Comparison of Post-Allogeneic Hematopoietic Cell Transplantation (HCT) Outcomes after Matched Related Donor Versus Matched Unrelated Donor HCT in Adults with Acute Lymphoblastic Leukemia

Allogeneic hematopoietic cell transplantation (HCT) is a potentially life-saving treatment for patients with acute lymphoblastic leukemia (ALL). About one-third of patients have a human leukocyte antigen (HLA) matched related donor (MRD), while the remaining two-thirds have either a fully HLA-matched (HLA-A, -B, -C, -DRB1 [8/8]) unrelated donor (MUD) or a MUD with a single HLA mismatch (7/8). Previous analyses by the CIBMTR have shown that MRD and MUD transplants produce similar survival outcomes for patients with acute myelogenous leukemia (AML) (Blood 2012; 119(17):3908-16), while donor source was an important predictor of outcomes in patients with myelodysplastic syndrome (MDS) (Blood 2013; 122(11):1974-82). Given that ALL represents the second most common indication for HCT, and recognizing the disease-specific nature of the impact of donor source on post-HCT outcomes previously described, we performed an analysis of outcomes after MRD versus MUD HCT in 1458 patients with ALL who underwent allogeneic HCT from 2000-2011 (MRD n=440, 8/8 MUD n=729, 7/8 MUD n=289). Median age was 37 years (18-69). Thirty-four percent were Philadelphia chromosome positive.Ten percent received reduced intensity conditioning (RIC). Twenty-three percent were transplanted in second complete remission (CR2).Seventy-four percent received peripheral blood stem cells. At 100 days post-HCT, the incidence of acute GVHD Grade B-D was significantly lower in MRD recipients than in 8/8 MUD or 7/8 MUD recipients (26%, 45%, 50%, respectively; p<0.001). In multivariate analysis, 8/8 MUD recipients had similar rates of transplant-related mortality (TRM) and overall survival (OS) (hazard ratio [HR] 1.16, p=0.225and HR 1.01, p=0.93, respectively) compared to MRD recipients; 7/8 MUD recipients had inferior TRM and OS when compared to both MRD recipients (HR 1.92, p<0.001 and HR 1.29, p=0.01, respectively) and 8/8 MUD recipients (HR 1.66, p<0.001 and HR 1.28, p=0.008, respectively).Recipients of peripheral blood transplants had inferior long-term survival (>24 months post-HCT) (HR=2.13, p=0.003) compared to bone marrow transplants. Compared to MRD, 8/8 MUD recipients had superior relapse rates (HR 0.77, p=0.02), while 7/8 MUD recipients had no difference (HR 0.75, p=0.05). There were no differences in leukemia-free survival (LFS) comparing 8/8 MUD recipients (HR 0.95, p=0.55) and 7/8 MUD recipients (HR 1.20, p=0.07) to MRD recipients (Table 2, Figure 1).Differences in survival were likely due to higher rates of acute GVHD and TRM in the 7/8 MUD group. We conclude that MRD and 8/8 MUD recipients have similar survival outcomes post-HCT, while 7/8 MUD recipients suffer inferior survival, demonstrating that donor source plays a large role in the quality of outcomes. While MRD remains the ideal donor source due to its lower incidence of acute GVHD,HCT from an 8/8 MUD is a good alternative to MRD transplant, given its comparable long-term survival outcomes. [Display omitted] [Display omitted] [Display omitted] DisclosuresSandmaier:Gilliad: Honoraria; ArevaMed: Honoraria; Jazz Pharmaceutical: Honoraria; Seattle Genetics: Honoraria; Abmit: Research Funding; Bellicum: Research Funding.

Abstract 17469: Expanding the Donor Pool in Pediatric Heart Transplant With a Novel Three Dimensional Technique

Introduction: Heart transplant (HTx) outcomes continue to improve although organs remain limited. Donor-recipient (DR) size matching is critical in pediatrics. Usually, centers apply a subjective donor weight (wt) range based on recipient chest x-ray. DR wt ratios may vary from 0.7–4. Hypothesis: A novel 3D tool can be used to predict ideal donor size. Methods: A library of 3D reconstructed normal hearts was created from CT/MRI data. A linear fit of normal heart volume vs. body wt was determined for wts up to 22.5kgs (R 2 =0.983). The linear fit was used to predict donor heart volumes and ideal donor wt. Similarly, pre and post HTx hearts were reconstructed from 3 infant pts undergoing HTx. Results: [Table] The library was used to predict ideal donor wt targeting 1:1 DR heart volume ratio. Pt A had cardiomegaly and an ideal DR wt ratio of 3.5, which may be outside a center’s usual range. While all 3 Pts had DR wt ratios &gt; 1, Pt A had a downsized graft while Pt B and C had upsized grafts (based purely on DR heart volumes). 3D reconstructions &gt; 1 week post HTx suggest the downsized graft became larger and upsized grafts smaller. Conclusion: 3D reconstruction has tremendous potential to improve DR size matching in HTx. As the virtual library grows, the ability to accurately predict DR heart volumes will improve. Further, retrospective analysis of transplant cases, wherein 3D matching was used, will allow us to predict the limits of under and oversizing. Finally, this technique has potential to allow “virtual transplantations” wherein we can model a particular donor (green) into a patient-specific recipient (red) and assess fit along with potential for mismatch related morbidity. [Figure]

A genome-wide association study of a global rice panel reveals resistance in Oryza sativa to root-knot nematodes.

The root-knot nematode Meloidogyne graminicola is one of the most serious nematode pests worldwide and represents a major constraint on rice production. While variation in the susceptibility of Asian rice (Oryza sativa) exists, so far no strong and reliable resistance has been reported. Quantitative trait loci for partial resistance have been reported but no underlying genes have been tagged or cloned. Here, 332 accessions of the Rice Diversity Panel 1 were assessed for gall formation, revealing large variation across all subpopulations of rice and higher susceptibility in temperate japonica accessions. Accessions Khao Pahk Maw and LD 24 appeared to be resistant, which was confirmed in large pot experiments where no galls were observed. Detailed observations on these two accessions revealed no nematodes inside the roots 2 days after inoculation and very few females after 17 days (5 in Khao Pahk Maw and <1 in LD 24, in comparison with >100 in the susceptible controls). These two cultivars appear ideal donors for breeding root-knot nematode resistance. A genome-wide association study revealed 11 quantitative trait loci, two of which are close to epistatic loci detected in the Bala x Azucena population. The discussion highlights a small number of candidate genes worth exploring further, in particular many genes with lectin domains and genes on chromosome 11 with homology to the Hordeum Mla locus.

Cardiac transplantation for older patients: Characteristics and outcomes in the septuagenarian population

With increasing age of patients with heart failure, it is important to understand the potential role for orthotopic heart transplant (OHT) in elderly patients. We examined recipient and donor characteristics and long-term outcomes of older recipients of OHT in the United States. Using the United Network for Organ Sharing database, we identified OHT recipients from the years 1987-2014 and stratified them by age 18-59 years old, 60-69 years old, and ≥70 years old. We compared baseline characteristics of recipients and donors and assessed outcomes across groups. During this period, 50,432 patients underwent OHT; 71.8% (n = 36,190) were 18-59 years old, 26.8% (n = 13,527) were 60-69 years old, and 1.4% (n = 715) were ≥70 years old. Comparing the ≥70 years old group and 60-69 years old group, older patients had higher rates of ischemic etiology (53.6% vs 44.9%) and baseline renal dysfunction (61.4% vs 56.4%) and at the time of OHT were less likely to be currently hospitalized (45.0% vs 50.9%) or supported with left ventricular assist device therapy (21.0% vs 28.3%). Older recipients received organs from older donors (median age 36 years old vs 30 years old) who were more likely to have diabetes and substance use. After OHT, the median length of stay was similar between groups. At 1 year, of patients alive, patients ≥70 years old had fewer rejection episodes (17.8%) compared with patients 60-69 years old (29.5%). The 5-year mortality was 26.9% for recipients 18-59 years old, 29.3% for recipients 60-69 years old, and 30.8% for recipients ≥70 years old. Despite advanced age and less ideal donors, OHT recipients in their 70s had similar outcomes to recipients in their 60s. Selected older patients should not routinely be excluded from consideration for OHT.

Bi-Pedicle Pre-Expended Forehead Flap for Facial Subunits Reconstruction

INTRODUCTION: The reconstruction for facial complex defect involved two subunits is always a tough problem for plastic surgeons because its extraordinary identity and the difficulties to find the ideal donor site with perfect matching tissues. Based on the facial aesthetic subunits theory emphasized by Menick,1 when a large defect involving more than one subunit occurred, to replace as each subunit rather than simply patching the entire defect often gives a superior result. The forehead flap is acknowledged as the best donor site for nose and other facial part reconstruction because of its ideal color and texture. In this paper, the authors suggest a Bi-pedicle Pre-expended Forehead Flap to overcome and improve the disadvantages of the forehead flap. MATERIALS AND METHODS: From clinic practice and review of the literature, the authors design Bi-pedicle Pre-expended Forehead Flap in 5 complex facial defect patients based on the special anatomy of supratrochlear artery. One side was for total nasal reconstruction, and the other for upper lip. The procedures included extended forehead skin expansion, single-stage nasal contouring and subunit plasty, pedicle division and restoration, and flap decoration. RESULTS: This improved flaps designing were applied in 5 cases with follow up. In all cases, flaps were survived with similar quality to the other part of face, and all patients were satisfied with their new appearance. CONCLUSION: Bi-pedicle Pre-expended Forehead Flap application in complex facial defects with two subunits reconstruction would be a new and ideal choice for the plastic surgeons. It provides the similar color, thickness, texture, pliability reconstruction with reliable blood supply and adequate tissue, without extra donor site, extra expansion time and less tolerance to the patients. What is more important, it provides the coverage according to the facial aesthetic subunits conception which leading to a better result and ideal appearance.

Does Traumatic Donor Cause of Death Influence Outcome after Lung Transplantation? A Single-Centre Analysis.

Background Owing to the shortage of donor organs in lung transplantation (LuTX), liberalization of donor selection criteria has been proposed. However, some studies suggested that donor traumatic brain damage might influence posttransplantation allograft function. This article aimed to investigate the association of donor cause of death (DCD) and outcome after LuTX. Methods A retrospective analysis of 186 consecutive double LuTXs at our institution from January 2000 to December 2008 was performed. DCD was categorized into traumatic brain injury (TBI) and nontraumatic brain injury (NTBI). In addition, NTBI was sub classified as spontaneous intracerebral bleeding (B), hypoxic brain damage (H), and intracerebral neoplasia (N). Results DCD was classified as TBI in 50 patients (26.9%) and NTBI in 136 patients (73.1%): B in 112 patients (60.2%), H in 21 patients (11.3%), and N in 3 patients (1.6%). Young male donors predominated in group TBI (mean age 36.0 ± 14.5 vs. 42.8 ± 10.7, p < 0.01; 29 males in the TBI group [58.0%] vs. 48 males in the NTBI group [35.3%], p < 0.01). Groups of DCD did not differ significantly by recipient age or gender, recipient diagnosis, donor ventilation time, or paO2/FiO2 before harvesting. TBI donors received significantly more blood (3.4 ± 3.8 vs. 1.8 ± 1.9, p = 0.03). A chest trauma was evident only in group T (n = 7 [3.7%] vs. 0 [0%], p < 0.001). Mode of donor death did not affect the following indices of graft function: length of postoperative ventilation, paO2/FiO2 ratio up to 48 hours, and lung function up to 36 months. One- and three-year survival was comparable with 84.4 and 70.4% for TBI donors versus 89.4% and 69.2% for NTBI donors. Five-year survival tended to be lower in the TBI group but did not reach statistical significance (43.4 vs. 53.9%). Conclusion This study indicates that traumatic DCD does not affect outcome after LuTX. These results can be achieved with an ideal donor management combined with an individual case-to-case evaluation by an experienced LuTX surgeon.