Results Of Clinical Transplantation Research Articles

Central Role of Galectin-3 at the Cross-Roads of Cardiac Inflammation and Fibrosis: Implications for Heart Failure and Transplantation

Cardiac inflammation and fibrosis are central pathogenic mechanisms leading to heart failure. Transplantation is still the treatment of choice for many patients undergoing end-stage heart failure who remain symptomatic despite optimal medical therapy. In spite of considerable progress, the molecular mechanisms linking inflammation, fibrosis and heart failure remain poorly understood. Galectin-3 (GAL3), a chimera-type member of the galectin family, has emerged as a critical mediator implicated in cardiac inflammatory, vascular and fibrotic processes through modulation of different cellular compartments including monocytes and macrophages, fibroblasts, endothelial cells and vascular smooth muscle cells via glycan-dependent or independent mechanisms. GAL3-driven circuits may hierarchically amplify cytokine production and function, immune cell activation and fibrosis cascades, influencing a wide range of cardiovascular disorders. Thus, GAL3 emerges as a potential therapeutic target to counteract aberrant inflammation and fibrosis during heart failure and a potential biomarker of heart failure and clinical outcome of heart transplantation.

Clinical profile and outcome of kidney transplantation at Muhimbili National Hospital, Tanzania

BackgroundKidney transplantation is the definitive treatment option for chronic kidney failure, offering improved quality of life and extended survival. Access to kidney transplantation is limited in the Sub-Saharan Africa (SSA) region, with only a few countries with established services. Tanzania started its program five years ago, for the sustainability of the program it is important to understand the outcome. Therefore, this study was conducted to determine the clinical outcomes and survival rates of kidney transplant recipients at Muhimbili National Hospital in Tanzania, in the absence of a national transplant registry, since the inception of the program.MethodsThis was a retrospective study conducted among kidney transplant recipients from live donors at Muhimbili National Hospital (MNH) between November 2017 and February 2022. Analyses were performed to assess baseline characteristics, post-transplant complications, and patient and graft survival.ResultsIn our study of 68 kidney transplant recipients, the majority of recipients were male (63.2%) with a mean age of 45.8 years and under medical insurance (88.2%). The predominant cause of CKD was hypertension (58.2%) with recipients undergoing dialysis for a mean duration of 14.4 months, and basiliximab being the most commonly used induction medication (57.3%). The majority of donors were males (64.7%) and had first-degree relationships with recipients (76.5%). Haploid HLA mismatch was observed in 36.8% of cases. One-year patient and graft survival rates were 91.2% and 96.7%, respectively, with infection being the primary cause of death (n = 5), and more than half of deceased patients died with a functioning graft (n = 4).ConclusionOur study underscores favorable one-year patient and graft outcomes among kidney transplant recipients at Muhimbili National Hospital, Tanzania. However, challenges persist, notably with infections posing ongoing difficulties for this cohort.

264.1: Innate allorecognition and clinical kidney transplantation outcomes.

264.1: Innate allorecognition and clinical kidney transplantation outcomes.

Clinical outcome of lung transplantation for chronic thromboembolic pulmonary hypertension

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is a type of pulmonary hypertension with a low incidence. Despite pulmonary endarterectomy(PEA) being the preferred treatment for CTEPH, for patients who failed medical therapy and who are not suitable candidates for PEA, lung transplantation (LT) is still the only effective treatment for end-stage CTEPH; however, there are currently very few reports on the efficacy of LT for CTEPH.MethodsWe retrospectively analyzed the clinical data of seven patients diagnosed with CTEPH between July 2019 and July 2021. The follow-up deadline was March, 2022.ResultsThe mean age at admission was 54 ± 12 years. The average value of mean pulmonary artery pressure (mPAP) was 40 ± 5 mmHg. The mean preoperative oxygenation index(PaO2/FiO2) was 203 ± 56 mm Hg. After evaluation, one patient underwent left LT and the rest underwent bilateral LT. Three patients received intraoperative veno-venous extracorporeal membrane oxygenation (ECMO) support, and four patients received intraoperative veno-arterial ECMO support. The average postoperative mPAP was 19 ± 4 mmHg. The mean postoperative oxygenation index(PaO2/FiO2) was 388 ± 83 mmHg. There was a significant difference between the preoperative and postoperative mPAP and oxygenation index(PaO2/FiO2). All patients recovered well and were discharged 37 ± 19 days postoperatively. The mean follow-up duration was 19 ± 8 months. There was no recurrence of CTEPH.ConclusionsLT is an effective treatment for end-stage CTEPH, which can improve cardiopulmonary function and quality of life and prolong survival. Patients who are unable to tolerate PEA should be considered for LT as early as possible when internal medicine failed.

Meniscal allograft transplantation: A matched-pair analysis reveals worse sportactivity level but similar clinical improvement and survival in women compared to men.

The aim of this study was to assess how gender might affect the clinical outcome and survival of meniscal allograft transplantation (MAT). A total of 358 patients (23.2% women, 76.8% men) were treated with fresh-frozen nonirradiated allografts implantated arthroscopically using a single- or double-tunnel technique without bone plugs and peripheral suture to the capsule with 'all-inside'stitches. Patients were evaluated at baseline and 2-year follow-up with the Lysholm score, visual analogue scale (VAS) pain, the Knee Osteoarthritis Outcome Score (KOOS) subscalesand Tegner score. Women presented higher body mass index (p < 0.0005), poorer baseline VAS (p = 0.012), Lysholm score (p = 0.005), KOOS symptom (p = 0.034) and KOOS pain (p = 0.030), Tegner score (preinjury and basal, p < 0.0001 and p = 0.002, respectively), a lower number of previous (p = 0.039) and concurrent (p = 0.001) anterior cruciate ligament reconstructionsand a higher number of concurrent procedures (p = 0.032) and distal femoral osteotomies (p = 0.024). Worse results were documented in women at 2 years, with lower Lysholm score(p = 0.024) and Tegner score(p = 0.007)and a lower clinical survival rate (p = 0.03) (67.5% vs.82.2%) in the overall patient cohort. However, the matched-pair analysis only confirmed a lower Tegner score value at 2 years (p = 0.016), while underlying the interplay of sex, ageand concomitant cartilage lesions in determining the clinical outcome. The analysis of this large series of patients affected by postmeniscectomy syndrome and treated with MAT revealed gender differences. While both genders benefited from a significant improvement, the female population presents more often with older age, concomitant cartilage lesionsand a lower activity level, all factors contributing towards a lower clinical success after MAT. Level III, comparative study.

Discussion to: Effects of Intraoperative Support Strategies on Endothelial Injury and Clinical Lung Transplant Outcomes

Discussion to: Effects of Intraoperative Support Strategies on Endothelial Injury and Clinical Lung Transplant Outcomes

Clinical Outcome of Amniotic Membrane Transplantation in Chemically Injured Eyes

Purpose: To evaluate the clinical outcome of Amniotic Membrane Transplantation (AMT) in chemically injured eyes for ocular surface reconstruction. Methods: A prospective study of 30 consecutive chemically injured eyes was performed from December 2022 to May 2023 in National Institute of Ophthalmology &amp; Hospital (NIO&amp;H), Dhaka, Bangladesh. Twenty-seven patients (30 eyes having corrosive chemical injuries) were included in the study according to the inclusion &amp; exclusion criteria. AMT was performed within 21 days of injury by single surgeon with modified surgical procedure. Post operative evaluation was done by Snellen chart, slit lamp biomicroscope and Schirmer-II test. Results: After 3 months of AMT, there was no pain or inflammation. Improvement of vision found in 20 (66.67%) of 30 eyes, 4 (13.33%) eyes of rest 10 eyes showed inaccurate Projection of Rays (PR) vision and rest 6 (20.0%) eyes of rest 10 eyes found deteriorated vision. Epithelialization occurred in all eyes. Twenty-four (80.0%) eyes had limbal stem cell deficiency and they experienced superficial corneal vascularization. Symblepharon was seen in 18 (60.0%) eyes, 6 (20.0%) of these 18 eyes developed marked conjunctival shortening with ankyloblepharon. None of the eyes showed perforation. Conclusions: AMT increases patient comfort and reduces inflammation. In mild burns, AMT alone restores corneal and conjunctival surfaces. In moderate to severe burns, it reduces conjunctival scarring sequelae, but does not prevent the sequelae of limbal stem cell deficiency that requires further limbal stem cell transplantation. In the acute stage, AMT has a protective role against the progressive melting and perforation. J.Natl.Inst.Ophthalmol.2023;6(1): 21-26

CD7 CAR-T Therapy Followed By a Second Transplant for T-Cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma Patients Who Relapsed after a Prior Transplant

Background The therapeutic options for patients with T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma (T-ALL/LBL) who relapse after hematopoietic stem cell transplantation (HSCT) are currently restricted. CD7-targeted chimeric antigen receptor (CAR) T-cell therapy provides a promising avenue towards remission, yet the long-term prognosis for these patients still needs to be improved. The advantages of progressing to a second transplant post-CAR-T treatment remain uncertain due to limited data. In this study, we analyzed the clinical characteristics and transplantation outcomes of 16 T-ALL/LBL patients who, having relapsed after their initial transplantation, achieved complete remission (CR) in bone marrow (BM) and CR/partial remission (PR) in extramedullary lesions via CD7 CAR-T therapy and then opted for a second allogeneic HSCT (allo-HSCT) at our center. Our aim is to explore strategies to enhance the survival rate of these patients. Methods From January 2021 to January 2023, we analyzed T-ALL/LBL patients who underwent second transplantation at Hebei Yanda Lu Daopei Hospital. The patients included in this study met the following criteria: they had relapsed following their first HSCT and had subsequently undergone CD7 CAR-T therapy prior to the second transplantation. The follow-up cut-off date was till June 1, 2023. The median follow-up duration after the second transplantation was 178 days, ranging from 9 to 500 days. Results A total of 16 patients including 13 with T-ALL and 3 with T-LBL were enrolled. There were 14 males and 2 females. The donor of first transplantation was autologous(n=3), sibling identical(n=2), unrelated donor(n=2), or haplo-identical (n=9). After the first transplantation, 8 patients relapsed in bone marrow (BM) and 8 relapsed both in BM and extramedullary sites. Of these, 13 patients received autologous CD7 CAR-T, one patient received donor-derived CD7 CAR-T, and one patient was treated with universal CAR-T cells. After the CD7 CAR-T therapy, all 16 patients (100%) achieved minimal residual disease (MRD)-negative CR in BM, and 6 out of 8 patients (75%) achieved CR in extramedullary lesions. Only two patients exhibited PR in the extramedullary lesions. The median age at the time of the second transplantation was 28 years (range 14-42 years). The median time from diagnosis to the second transplantation was 683 days (range 385-2672 days). The median interval between the first and second transplantation was 438 days (range 229-2540 days), and the median interval from CD7 CAR-T infusion to the second transplantation was 72 days (range 31-92 days). For the second transplantation, 13 cases had haplo-identical donors and 3 cases had unrelated donors. The conditioning regimens utilized were either total body irradiation (TBI)-based (n=9), busulfan-based (n=6), or melphalan-based (n=1). Following the 2 nd transplant, the 1-year overall survival(OS) and leukemia-free survival(LFS) were 58.5% (95% CI, 28.9-85.0%) and 51.4% (95% CI, 22.4-79.9%), respectively(Figure 1). The 1-year relapse incidence (RI) and non-relapse mortality (NRM) were 15.9% (95% CI, 4.4-57.8%) and 31.5% (95% CI, 13.2-74.9%), respectively. The cumulative incidence of CMV and EBV viremia at day 100 were 75.0% (95% CI, 56.5-99.5%) and 19.8% (95% CI, 7.2-54.6%), respectively. The cumulative incidence of all grades acute graft-versus-host disease (aGVHD) and 3-4 grade aGVHD at day 100 were 56.3% (95%CI, 36.5-86.7%) and 25% (95%CI, 10.7-58.4%), respectively. One-year chronic GVHD(cGVHD) was observed in 25.1% of the cases (95%CI, 9.3-67.4%), while moderate to severe cGVHD was not found in any patient. Following the 2 nd transplant, a total of 6 patients died, including 3 from infection, 2 from relapse and 1 from intracranial hemorrhage. Conclusions Our initial findings suggest that even in refractory/relapsed T-ALL/LBL patients who have experienced relapse following previous HSCT, MRD-negative complete remission can potentially be achieved utilizing CD7 CAR-T cell therapy. The subsequent implementation of a second allo-HSCT appears feasible. Combining CAR-T therapy with a follow-up second HSCT presents a strategy for these heavily pre-treated patients, offering promising prospects for survival. However, further evaluation of this treatment approach is required, necessitating long-term monitoring and a larger patient cohort.

The clinical outcome of sequential liver-kidney transplantation

The clinical outcome of sequential liver-kidney transplantation

Comparison of Therapeutic Effects between Young Haploidentical Donors and Elderly HLA-Matched Relative Donors for AML Patients Who Undergoing Allogeneic Hematopoietic Stem Cell Transplantation with Conditioning Regime Including ATG

Objective: Donor selection is one of the issues faced in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aims to compare the impact of young haploidentical donors and elderly matched relative donors on the outcomes of AML patients undergoing allo-HSCT with conditioning regime including ATG, providing reference for donor selection. Methods: A retrospective analysis was conducted on 708 AML patients who underwent allo-HSCT at our hospital from 2014 to 2021. Among them, 354 patients were included in this study, with 289 patients receiving haploidentical transplantation from donors under the age of 50 (haplo group) and 65 patients receiving fully matched sibling transplantation from donors over the age of 50 (MSD group). Clinical characteristics and transplantation outcomes of both groups of patients and donors were compared. Results: Among the 354 AML-MRC patients, there were 178 males and 176 females, with a median age of 41 (18~56) years. The median follow-up time was 35 (95% CI 30~49) months, and the median overall survival (OS) was 78 (95% CI 23~) months. The 3-year OS rate was 63.1% (95% CI 45.6%~81.4%), the 3-year event-free survival (EFS) rate was 59.0% (95% CI 40.8%~66.1%), the cumulative incidence of relapse (CIR) was 26.8% (95% CI 16.6%~30.0%), and the transplantation-related mortality (TRM) was 22.7% (95% CI 13.2%~33.8%). There were no statistically significant baseline differences between the haplo group and MSD group. The 3-year OS rates for haplo group vs. MSD group were 0.660 (95% CI 0.597-0.731) vs. 0.670 (95% CI 0.558-0.806) (p=0.7), the 3-year EFS rates were 0.620 (95% CI 0.543-0.720) vs. 0.570 (95% CI 0.458-0.656) (p=0.6), and the TRM rates were 0.165 (95% CI 0.121-0.282) vs. 0.134 (95% CI 0.062-0.234) (p=0.6). The CIR rates were 0.199 (95% CI 0.147-0.250) vs. 0.275 (95% CI 0.165-0.397) (p=0.196), and the cumulative incidence of grade II-IV aGVHD was 0.288 (0.237-0.342) vs. 0.309 (95% 0.200-0.424) (P=0.891). The incidence of cGVHD was 0.140 (0.099-0.188) vs. 0.250 (95% 0.147-0.367) (p=0.032). Conclusion: For AML patients undergoing allo-HSCT with conditioning regime including ATG, compared to elderly fully matched donors, young haploidentical donors may reduce the occurrence of post-transplant cGHVD.

Clinical characteristics of 15 cases of renal transplantation with pre-exsiting donor-specific antibody.

Currently, patients with pre-exsiting donor-specific antibody (DSA) are prone to antibody-mediated rejection (AMR) after surgery and are at a relatively high risk of postoperative complications and graft failure. The risk of postoperative complications and graft failure is relatively high. This study aims to discuss the clinical outcome of DSA-positive kidney transplantation and analyze the role and safety of preoperative pretreatment in DSA-positive kidney transplantation, providing single-center treatment experience for DSA-positive kidney transplantation. We retrospectively analyzed the clinical data of 15 DSA-positive kidney transplants in the Department of Renal Transplantation of First Affiliated Hospital of Zhengzhou University from August 2017 to July 2022. Eight cases were organ donation after citizen's death (DCD) kidney transplant recipients, of which 3 cases in the early stage were not treated with preoperative desensitisation therapy (DCD untreated group, n=3), and 5 recipients were treated with preoperative rituximab desensitisation (DCD preprocessing group, n=5). The remaining 7 cases were living related donors recipients (LRD) who received preoperative desensitisation treatment with rituximab and plasma exchange (LRD preprocessing group, n=7). We observed and recorded the incidence of complications with changes in renal function and DSA levels in the recipients and the survival of the recipients and transplanted kidneys at 1, 3 and 5 years, and to compare the differences in recovery and postoperative complications between 3 groups. All 15 recipients were positive for preoperative panel reactive antibody (PRA) and DSA and were treated with methylprednisolone+rabbit anti-human thymocyte immunoglobulin induction before kidney transplantation. DCD untreated group all suffered from DSA level rebound, delayed renal graft function (DGF) and rejection reaction after surgery. After the combined treatment, DSA level was reduced and the graft renal function returned to normal. The DCD preprocessing group were all without antibody rebound, 1 recipient developed DGF and the renal function returned to normal after plasmapheresis, and the remaining 4 recipients recovered their renal function to normal within 2 weeks after the operation. In the LRD preprocessing group, 2 cases had antibody rebound and 1 case had rejection, but all of them recovered to normal after treatment, and DSA was maintained at a low level or even disappeared. The incidence of DGF and rejection in the DCD untreated group were significantly higher than that in the DCD preprocessing group and the LRD preprocessing group; and there were no significant difference in the incidence of postoperative haematuria, proteinuria, bacterial and fungal infections, and BK virus infection between the 3 groups (all P>0.05). A total of 11 of the 15 recipients were followed up for more than 1 year, 6 for more than 3 years, and 1 for more than 5 years, and the survival rates of both the recipients and the transplanted kidneys were 100%. Effective preoperative pretreatment with desensitization therapy can effectively prevent antibody rebound in DSA-positive kidney transplantation and reduce perioperative complications.

Deceased Donor Flush Volume Similar for Histidine-Tryptophan-Ketoglutarate and University of Wisconsin at a Single US Organ Procurement Organization: Adult and Pediatric Data

Histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solutions are the two primary solid-organ preservation solutions used in the United States (>95%), but flush volumes vary markedly by region and center. This study analyzes data from a single organ procurement organization (OPO) to determine the actual clinical flush volumes used for HTK and UW for liver and pancreas grafts. All procurements at Indiana Donor Network were analyzed (2016-2020), and data were extracted from the on-site records. Variables included procuring center, solution, volumes, and vessels flushed. Brand and generic versions were considered equivalent. No clinical transplant outcomes were available. Data were analyzed from 875 liver and 192 pancreas procurements by over 70 U.S. centers representing 10 of 11 UNOS regions. The large majority of liver grafts were preserved with HTK (n=810, 93%; UW n=93, 7%). All liver donors received an aortic flush (100%), while portal vein flush was 14% in-situ and 88% back table. For liver grafts, the median volume of infused solution was less for HTK when compared to UW (4225mL vs 5500mL, p=0.04). For pancreas procurement, 100% received aortic flush of the graft, with median HTK and UW volumes being equivalent (3000mL; p=0.85). Pediatric organs were flushed with markedly higher weight-based volumes. Flush volumes for HTK and UW are similar at one midwestern OPO, with data comprised of procurements performed by centers from across the U.S. These data demonstrate that low-volume HTK flush is commonly used, and this practice may be considered as a cost-saving measure.

Transfused Red Blood Cell Characteristics and Kidney Transplant Outcomes Among Patients Receiving Early Posttransplant Transfusion

Red blood cell transfusion (RBCT) is frequently required in the early post-kidney transplant period, but long-term outcomes associated with RBCT is controversial. Therefore, it may be relevant to investigate the association between RBCT characteristics and transplant outcomes. To study the association between RBC storage duration and transplant outcomes. This was a nationwide retrospective cohort study based on data linking between 2 prospective French nationwide registries. Clinical transplant parameters, outcomes, and RBCT characteristics were extracted from the CRISTAL registry of the Agence de la Biomédecine and the national database of the Etablissement Français du Sang. All 12 559 patients having received a first kidney transplant in France between January 1, 2002, and December 31, 2008, were included. Patients were followed up from transplant to graft loss, death with a functional graft, or data retrieval in June 2016. Data were analyzed from April 2019 to June 2022. Clinical outcomes of transplant recipients who underwent early RBCT were analyzed considering transfusion characteristics. Cox proportional hazards regression models were fitted to evaluate transplant failure defined as graft loss or death with a functional graft. Among 12 559 patients who underwent kidney transplant, 3483 received an RBCT during the first 14 days posttransplant. The median (IQR) age of patients was 53.0 (41.5-61.2) years, and 1929 patients (55.4%) were male. Median (IQR) follow-up was 7.8 (7.6-8.0) years. In multivariable analysis, longer (vs shorter) storage duration of transfused RBC was associated with a decrease in risk of transplant failure (hazard ratio, 0.99; 95% CI, 0.98-1.00 for each additional storage day; P = .06). Patients transfused with at least 1 RBC unit stored for more than 20 days had a 5% absolute decrease in transplant failure at 3 years and 7% at 5 years compared with those who received RBC stored for less than 20 days. In this study, longer RBC storage duration was associated with a decreased risk of transplant failure among patients who received kidney transplants and RBC transfusions. Preferential use of RBC with longer storage duration might improve kidney graft survival following transplant and transfusion.

Hybrid structural modeling of alloantibody binding to human leukocyte antigen with rapid and reproducible cross-linking mass spectrometry

Alloantibody recognition of donor human leukocyte antigen (HLA) is associated with poor clinical transplantation outcomes. However, the molecular and structural basis for the alloantibody-HLA interaction is not well understood. Here, we used a hybrid structural modeling approach on a previously studied alloantibody-HLA interacting pair with inputs from ab initio, in silico, and invitro data. Highly reproducible cross-linking mass spectrometry data were obtained with both discovery- and targeted mass spectrometry-based approaches approaches. The cross-link information was then used together with predicted antibody Fv structure, predicted antibody paratope, and in silico-predicted interacting surface to model the antibody-HLA interaction. This hybrid structural modeling approach closely recapitulates the key interacting residues from a previously solved crystal structure of an alloantibody-HLA-A∗11:01 pair. These results suggest that a predictive-based hybrid structural modeling approach supplemented with cross-linking mass spectrometry data can provide functionally relevant structural models to understand the structural basis of antibody-HLA mismatch in transplantation.

Clinical Outcome of Amniotic Membrane Transplant in Ocular Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis at a Major Burn Unit

To analyze the clinical outcome of amniotic membrane transplantation in patients with ocular Stevens-Johnson syndrome/toxic epidermal necrolysis at a major burn unit. Retrospective, non-randomized interventional study. A retrospective chart review from April 2014 to January 2022 of 43 patients (85 eyes) at a burn center who underwent amniotic membrane transplantation (AMT) for severe ocular Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), or SJS/TEN was performed. Data regarding the clinical course and outcome were obtained. A comparison between the use of cryopreserved AMT rings (cryoAMT) and dehydrated AMT (deAMT) was also assessed. A total of 85 eyes in 43 patients underwent AMT for severe ocular SJS/TEN. Of the eyes, 72 received deAMT with symblepharon ring, whereas 13 received cryoAMT over the cornea surface. All patients had deAMT placed over the eyelid margins and palpebral conjunctivae and tucked into the fornices. The average best-corrected visual acuity (BCVA) on last follow-up examination was 20/33, 20/30, and 20/34 in all eyes, the cryoAMT group, and the deAMT group, respectively (no significant difference between groups). The most common suspected inciting agent was lamotrigine (17% of all cases). The average long-term complication score was 1.4, with no significant difference between the cryoAMT group (1.6) and the deAMT group (1.4, P=.5). Symblepharon formation was seen more in the cryoAMT group compared to the deAMT group (P < .05). The use of AMTs in severe ocular SJS/TEN greatly mitigates long-term complications and improves visual outcome. The retrospective nature of this study limits substantial conclusions regarding any significant difference in outcome between AMT treatment methods. Nevertheless, the use of cryopreserved AMT rings has a similar outcome profile compared to use of dehydrated AMTs with symblepharon ring. Further research is needed to evaluate optimal AMT techniques.

Purine Nucleoside Phosphorylase Deficient Severe Combined Immunodeficiencies: A Case Report and Systematic Review (1975-2022).

Purine nucleoside phosphorylase deficient severe combined immunodeficiency (PNP SCID) is one of the rare autosomal recessive primary immunodeficiency disease, and the data on epidemiology and outcome are limited. We report the successful management of a child with PNP SCID and present a systematic literature review of published case reports, case series, and cohort studies on PNP SCID listed in PubMed, Web of Science, and Scopus from 1975 until March 2022. Forty-one articles were included from the 2432 articles retrieved and included 100 PNP SCID patients worldwide. Most patients presented with recurrent infections, hypogammaglobulinaemia, autoimmune manifestations, and neurological deficits. There were six reported cases of associated malignancies, mainly lymphomas. Twenty-two patients had undergone allogeneic hematopoietic stem cell transplantation with full donor chimerism seen mainly in those receiving matched sibling donors and/or conditioning chemotherapy before the transplant. This research provides a contemporary, comprehensive overview on clinical manifestations, epidemiology, genotype mutations, and transplant outcome of PNP SCID. These data highlight the importance of screening for PNP SCID in cases presented with recurrent infections, hypogammaglobulinaemia, and neurological deficits.

Donor Pericardial Interleukin and Apolipoprotein Levels May Predict the Outcome after Human Orthotopic Heart Transplantation

The proinflammatory cascade that is activated at the time of brain death plays a crucial role in organ procurement. Our aim of this study was to explore the relationship between the clinical outcome of orthotopic heart transplantation, as well as cytokine and apolipoprotein profiles of the pericardial fluid obtained at donation. Interleukin, adipokine and lipoprotein levels in the pericardial fluid, as well as clinical data of twenty donors after brain death, were investigated. Outcome variables included primary graft dysfunction, the need for posttransplantation mechanical cardiac support and International Society for Heart and Lung Transplantation grade ≥ 2R rejection. Hormone management and donor risk scores were also investigated. Lower levels of IL-6 were observed in primary graft dysfunction (median: 36.72 [IQR: 19.47-62.90] versus 183.67 [41.21-452.56]; p = 0.029) and in the need for mechanical cardiac support (44.12 [20.12-85.70] versus 247.13 [38.51-510.38]; p = 0.043). Rejection was associated with lower ApoAII (p = 0.021), ApoB100 (p = 0.032) and ApoM levels (p = 0.025). Lower adipsin levels were detected in those patients receiving desmopressin (p = 0.037); moreover, lower leptin levels were found in those patients receiving glucocorticoid therapy (p = 0.045), and higher T3 levels were found in those patients treated with L-thyroxine (p = 0.047) compared to those patients not receiving these hormone replacement therapies. IL-5 levels were significantly associated with UNOS-D score (p = 0.004), Heart Donor Score (HDS) and Adapted HDS (p < 0.001). The monitoring of immunological and metabolic changes in donors after brain death may help in the prediction of potential complications after heart transplantation, thus potentially optimizing donor heart allocation.

Effects of Intraoperative Support Strategies on Endothelial Injury and Clinical Lung Transplant Outcomes

In lung transplantation, postoperative outcomes favor intraoperative use of extracorporeal membrane oxygenation (ECMO) over cardiopulmonary bypass (CBP). We investigated the effect of intraoperative support strategies on endothelial injury biomarkers and short-term posttransplant outcomes. Adults undergoing bilateral lung transplantation with No-Support, venoarterial (V-A) ECMO, or CPB were included. Plasma samples pre- and post-transplant were collected for Luminex assay to measure endothelial injury biomarkers including syndecan-1 (SYN-1), intercellular adhesion molecule-1 (ICAM-1), and matrix metalloprotease-9. Fifty five patients were included for analysis. The plasma level of SYN-1 at arrival in the intensive care unit was significantly higher with CPB compared to V-A ECMO and No-Support (P < 0.01). The rate of primary graft dysfunction grade 3 (PGD3) at 72 hours was 60.0% in CPB, 40.1% in V-A ECMO, and 15% in No-Support (P = 0.01). Postoperative plasma levels of SYN-1 and ICAM-1 were significantly higher in recipients who developed PGD3 at 72 hours. SYN-1 levels were also significantly higher in patients who developed acute kidney injury and hepatic dysfunction after transplant. Postoperative, SYN-1 upon intensive care arrival was found to be a significant predictive biomarker of PGD3, acute kidney injury, and hepatic dysfunction following lung transplantation. CPB is associated with higher plasma concentrations of SYN-1, a marker of endothelial glycocalyx degradation, upon arrival to the intensive care unit. Higher levels of SYN-1 are predictive of end-organ dysfunction following lung transplantation. Our data suggests that intraoperative strategies aimed at modulating endothelial injury will help improve lung transplantation outcomes.

The frequencies of lymphocyte subsets on “day 30″ correlate with the clinical outcome of pediatric hematopoietic stem cell transplantation

We aimed to determine the relationship between lymphocyte subsets on day 30 (D30) and prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. We retrospectively examined the clinical outcomes and lymphocyte subsets on D30 after allo-HSCT in 115 pediatric patients at the Children's Hospital of Soochow University between January 2016 and June 2019. Measurements were performed using flow cytometry on D30. Lymphocyte subsets were compared among the umbilical cord blood (UCB) (n = 22), HLA-matched sibling donor (MSD) (n = 14), haploidentical donor transplantation (HID) (n = 57), and unrelated donor transplantation (UD) (n = 22) groups. The relationships between the frequencies and counts of lymphocyte subsets and clinical outcomes were analyzed. T and B cell counts were the highest in the MSD group compared to the other groups, and natural killer cell counts were the highest in the UCB group. Lymphocyte subsets on D30 after allo-HSCT were correlated with the occurrence of acute (aGVHD) and chronic graft versus host disease (cGVHD). A high frequency of B cells (≥4.65%) was associated with the development of severe aGVHD. High frequencies of CD4+T (≥10.25%) were correlated with extensive cGVHD. Moreover, a high frequency of CD4+T cells (≥9.80%) was correlated with GVHD-free and failure-free survival (GFFS) after allo-HSCT. However, on D30, there were no statistically significant correlations between viral infections and lymphocyte subsets. The frequencies of lymphocyte subsets on D30 after allo-HSCT are good indicators of prognosis after allo-HSCT in children.

Early Postoperative CT Scan Provides Prognostic Data on Clinical Outcomes of Fresh Osteochondral Transplantation of the Knee

Background: There is a lack of information regarding the ability of imaging studies to predict clinical outcomes after fresh osteochondral allograft (FOCA) transplantation of the knee. Purpose: To determine the value of computed tomography (CT) scans to predict the clinical outcome of FOCA transplantation using the assessment computed tomography osteochondral allograft (ACTOCA) score. Study Design: Cohort study; Level of evidence, 3. Methods: We prospectively collected data from all consecutive patients who underwent FOCA transplantation for osteochondral knee lesions at one institution between August 2017 and August 2019. All patients were followed up for a minimum of 2 years. CT scans performed 6 months after surgery were evaluated by a musculoskeletal radiologist using the ACTOCA scoring system. The radiologist was blinded to the patient’s medical history. Clinical outcomes were assessed preoperatively and at 12 and 30 months postoperatively using the International Knee Documentation Committee (IKDC) score, the Kujala score, the Tegner activity scale, and the Western Ontario Meniscal Evaluation Tool (WOMET) score. Results: A total of 38 cases were included. The ACTOCA score at 6 months after surgery showed a statistically significant correlation with clinical results at 12 and 30 months. The correlation was better at 30 months, showing a high negative correlation with the IKDC score (−0.663) and a moderate negative correlation with the Kujala, WOMET, and Tegner scores (−0.593; −0.547, and −0.593, respectively) (P < .001). Conclusion: A statistically significant correlation between the mean ACTOCA score on CT scans at 6 months and the clinical results measured by the IKDC, Kujala, WOMET, and Tegner scores at 30 months confirmed the predictive value of the ACTOCA score for use in clinical practice.