Evaluation of custom-made relay® stent-grafts for aortic arch landing zones 0 and I: experience from two high-volume aortic centers.

OBJECTIVES: To report experience with a Relay® stent graft custom-made platform in treating different aortic arch pathology in two high-volume aortic centers. METHODS: a retrospective analysis of all patients treated between July 2016 and July 2023 with custom-made Relay® stent graft (CMD). Underlying aortic arch pathology was aneurysm, penetrating aortic ulcer (PAU) and dissection. Three CMD designs were used: proximal scallop, fenestrations, and inner branches. Endpoints were technical success, perioperative stroke, death, and reintervention rate. RESULTS: 35 patients (89% males) with a mean age of 70 ± 11 years were treated.Indication for treatment was PAU in 14 patients (40%), aneurysm in eleven patients (31%), and ten patients (29%) had aortic dissection. Technical success rate was 100%. Twenty-eight patients (80%) had proximal sealing in zone 0 and seven (20%) in zone 1. Nine patients (25.6%) had proximal scallops, nine (25.6%) one big fenestration and 17 (48.8%) a branched device; one with single branch; 15 with double branches and one with triple branches. Thirty patients (86%) had previous or simultaneous LSA revascularization. No patient died during 30-days. Two patients (5.7%) had stroke postoperatively; both recovered without disabling deficits. Mean follow-up was 35 ± 26 months. Six patients (17.1%) died during follow-up. One patient required reinforcement of the bridging stent in the LCCA and one additional vascular pluging of the LSA. Three patients received distal extension. CONCLUSIONS: The Relay® stent graft custom-made platform showed a good performance in our study with high technical success rate, low perioperative stroke and mortality, and low reintervention rates during the follow-up.

The Alar Extension Graft Technique for the Treatment of External Nasal Valve Collapse: Preliminary Results of a Single-Centre Prospective Analysis.

BACKGROUND: The aim of this study is to describe the efficacy of the alar extension graft for the correction of external nasal valve collapse and to evaluate the functional and aesthetic results. METHODS: The study included 51 patients who underwent alar extension grafting for external nasal valve collapse. Pre- and post-operative rhinomanometry was performed before and after surgery. NOSE and SNOT 20 questionnaires were completed before and 9 months after surgery. Patients were also asked about their post-operative satisfaction. RESULTS: 90% of patients were subjectively satisfied with the post-operative improvement in nasal breathing. There was a significant improvement in the values of the pre- and post-operative NOSE and SNOT 20 questionnaire scores. Rhinomanometry showed increased nasal flow with a statistically significant difference between pre- and post-operative results. CONCLUSIONS: The alar extension graft has been proved to be effective and reliable in the surgical treatment of external nasal valve collapse, improving the patients' objective and subjective breathing with good functional and aesthetic results. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Unravelling the potential of TIM-3 gene polymorphism in allogeneic hematopoietic stem cell transplantation - a preliminary study.

BACKGROUND: T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) molecule is a key regulator of the immune response by exerting an inhibitory effect on various types of immune cells. Understanding the role of TIM-3 in hematopoietic stem cell transplantation (HSCT) may improve transplant outcomes. Our study evaluated the potential association between TIM-3 polymorphisms, namely rs1036199 (A > C) or rs10515746 (C > A), changes which are located in exon 3 and the promoter region of the TIM-3 gene, and post-HSCT outcomes. METHODS: One-hundred and twenty allogeneic HSCT patients and their respective donors were enrolled and genotyped for TIM-3 single nucleotide polymorphisms (SNPs) using real-time PCR with TaqMan assays. RESULTS: We found that the presence of the rare alleles and heterozygous genotypes of studied SNP in recipients tended to protect against or increase the risk for acute graft-versus-host disease (aGvHD). For the rs1036199 polymorphism, recipients with the AC heterozygous genotype (p = 0.0287) or carrying the rarer C allele (p = 0.0334) showed a lower frequency of aGvHD development along all I-IV grades. A similar association was detected for the rs10515746 polymorphism as recipients with the CA genotype (p = 0.0095) or the recessive A allele (p = 0.0117) less frequently developed aGvHD. Furthermore, the rarer A allele of rs10515746 SNP was also associated with a prolonged aGvHD-free survival (p = 0.0424). Cytomegalovirus (CMV) infection was more common in patients transplanted with TIM-3 rs10515746 mismatched donors (p = 0.0229) and this association was also found to be independent of HLA incompatibility and pre-transplant CMV-IgG status. Multivariate analyses confirmed the role of these recessive alleles and TIM-3 incompatibility as an independent factor in aGvHD and CMV development. CONCLUSIONS: Polymorphism of TIM-3 molecule may affect the immune response in HSCT patients. The recessive alleles of rs1036199 and rs10515746 SNPs decreased the risk of developing aGvHD. TIM-3 donor-recipient genetic matching may also affect the risk of post-transplant CMV infection, indicating the potential value of genetic profiling in optimizing transplant strategies.

Allostimulation leads to emergence of a human B cell population with increased expression of HLA class I antigen presentation associated molecules and the immunoglobulin receptor FcRL5.

In the extensive literature characterizing lymphocyte contributions to transplant-related pathologies including allograft rejection and graft-versus-host disease, T cell-focused investigation has outpaced investigation of B cells. Most B cell-related reports describe regulatory and antibody-producing functions, with less focus on the potential role of antigen-presenting capacity. Using in vitro human mixed lymphocyte reactions (MLRs) to model allostimulation, we analyzed responder B cells using transcriptional analysis, flow cytometry and microscopy. We observed emergence of an activated responder B cell subpopulation phenotypically similar to that described in individuals with graft-versus-host disease or allograft rejection. This population had markedly increased expression of FcRL5 (Fc receptor like 5) and molecules associated with HLA class I antigen presentation. Consistent with this phenotype, these cells demonstrated increased internalization of irradiated cell debris and dextran macromolecules. The proportion of this subpopulation within MLR responders also correlated with emergence of activated, cytotoxic CD8+ T cells. B cells of similar profile were quite infrequent in unstimulated blood from healthy individuals but readily identifiable in disaggregated human splenocytes and increased in both cases upon allostimulation. Further characterization of the emergence and function of this subpopulation could potentially contribute to identification of novel biomarkers and targeted therapeutics relevant to curbing transplant-related pathology.

Isolation of the Stromal Vascular Fraction Using a New Protocol with All Clinical-Grade Drugs: From Basic Study to Clinical Application.

OBJECTIVE: The purpose of this study was to evaluate the yield, viability, clinical safety, and efficacy of the stromal vascular fraction (SVF) separated with a new protocol with all clinical-grade drugs. MATERIALS AND METHODS: SVF cells were isolated from lipoaspirate obtained from 13 participants aged from 30 to 56 years by using a new clinical protocol and the laboratory protocol. The cell yield, viability, morphology, mesenchymal stem cell (MSC) surface marker expression, and differentiation abilities of the SVF cells harvested from the two protocols were compared. Furthermore, three related clinical trials were conducted to verify the safety and efficiency of SVF cells isolated by the new clinical protocol. RESULTS: There were no significant differences in the yield, viability, morphology, and differentiation potential of the SVFs isolated with the clinical protocol and laboratory protocol. Adipose-derived mesenchymal stem cell (ASC) surface marker expression, including that of CD14, CD31, CD44, CD90, CD105, and CD133, was consistent between the two protocols. Clinical trials have demonstrated the effectiveness of the SVF isolated with the new clinical protocol in improving skin grafting, promoting mechanical stretch-induced skin regeneration and improving facial skin texture. No complications occurred. CONCLUSION: SVF isolated by the new clinical protocol had a noninferior yield and viability to that of the SVF separated by the laboratory protocol. SVFs obtained by the new protocol can be safely and effectively applied to improve skin grafting, promote mechanical stretch-induced skin regeneration, and improve facial skin texture. TRIAL REGISTRATION: The trials were registered with the ClinicalTrials.gov (NCT03189628), the Chinese Clinical Trial Registry (ChiCTR2000039317), and the ClinicalTrials.gov (NCT02546882). All the three trials were not patient-funded trials. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Cross-Facial Nerve Grafting Used Independently in Facial Reanimation: A Narrative Review.

Importance: Cross-Facial Nerve Grafting (CFNG) for facial palsy offers potential to restore spontaneous facial expression, but specific indications and associated outcomes are limited. Updates to this technique have aided in its successful employment in select cases. This review aims to explore the context in which CFNG has been successfully utilized as a primary modality. Observations: Literature review was performed auditing all studies investigating CFNG as a primary modality, which reported outcomes. A total of 326 cases reporting outcomes for primary CFNG were included. Eye closure outcomes were 83.3% successful at ages 0-18, 77.3% successful at ages 19-40, and 57.1% successful at ages 41+. Smile outcomes were 73.7% successful at ages 0-18, 81.5% successful at ages 19-40, and 52.8% successful at ages 41+. For synkinesis, 89% of cases were considered successful; 100% successful at ages 0-18, and 78.4% successful in adults. Conclusions and Relevance: CFNG may offer return of spontaneous facial function in select cases. Higher percentages of successful outcomes are observed in younger patients, when performed in two stages, and when performed earlier from the onset of FP in cases of eye closure restoration. In the modern era, CFNG has been more commonly employed as an adjunctive procedure to other reanimation techniques.

First Report of Two-stage Living Donor Liver Transplantation to Avoid Futility and Ensure Double Equipoise in Acute Liver Failure Complicated by Toxic Liver Syndrome.

Acute hepatic failure may occasionally be complicated by toxic liver syndrome. Emergency hepatectomy for stabilization followed by delayed graft implantation is a recognized strategy in such cases in the setting of deceased donor liver transplantation. Living donor liver transplantation adds additional complexity to this scenario as the donor liver is a directed donation and failure to stabilize the patient after emergency hepatectomy can lead to a futile live donor hepatectomy, hepar-divisum, or an orphan graft. We report a case where the two-stage strategy was utilized to circumvent this situation. A patient with toxic liver syndrome underwent emergency hepatectomy and was closely monitored in the operating theater. A live donor hepatectomy was started after the recipient demonstrated cardiovascular and neurological stabilization. Graft implantation was completed after an anhepatic period of 9.45 h. To our knowledge, this is the first reported instance of using the two-stage strategy in living-donor-liver-transplantation for toxic liver syndrome to prevent futile donor surgery and achieve double equipoise.

Collagen-Type Composition in the Semitendinosus, Quadriceps, and Patellar Tendons of a 22-Year-Old Patient: A Case Report.

Graft failure is a common postoperative complication after anterior cruciate ligament (ACL) reconstruction. Recently, a theory has emerged that histological and microstructural factors of autografts may be related to graft failure. We simultaneously collected the semitendinosus tendon (ST), quadriceps tendon (QT), and patellar tendon (PT) from a 22-year-old patient to provide insights into the differences in the collagen-type composition of the three tendons in skeletally mature patients. These findings may serve as a basis for selecting autografts for ACL to reduce graft failure rates. The patient was a 22-year-old female who required the removal of artificial ligament, screws, and washers and medial patellofemoral ligament (MPFL) reconstruction with an ST autograft after two surgeries for recurrent dislocation of the left patella. The ST, QT, and PT obtained during necessary intraoperative procedures were used as samples. The tissues were processed and immunostained; this was followed by confocal microscopy. Evaluation was performed by calculating the percentage of areas positive for collagen types I and III.The percentage of type I collagen in the ST, QT, and PT groups was 88%, 85%, and 88%, respectively.The collagen-type composition was examined following simultaneous collection of the ST, QT, and PT. The results revealed no significant differences in the content of physically strong type I collagen, which supports previous findings showing that the clinical outcomes after ACL reconstruction do not vary with the autograft used.

Efficacy of using autologous cells with graft substitutes for spinal fusion surgery: A systematic review and meta-analysis of clinical outcomes and imaging features.

Over the past several decades, there has been a notable increase in the total number of spinal fusion procedures worldwide. Advanced spinal fusion techniques, surgical approaches, and new alternatives in grafting materials and implants, as well as autologous cellular therapies, have been widely employed for treating spinal diseases. While the potential of cellular therapies to yield better clinical results is appealing, supportive data are needed to confirm this claim. This meta-analysis aims to compare the radiographic and clinical outcomes between graft substitutes with autologous cell therapies and graft substitutes alone. PubMed, Scopus, Web of Science, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials were searched for studies comparing graft substitutes with autologous cell therapies and graft substitutes alone up to February 2024. The risk of bias of the included studies was evaluated using the Downs and Black checklist. The following outcomes were extracted for comparison: fusion success, complications/adverse events, Visual Analog Scale (VAS) score, and Oswestry Disability Index (ODI) score. Thirteen studies involving 836 patients were included, with 7 studies considered for the meta-analysis. Results indicated that the use of graft substitutes with autologous cell therapies demonstrated higher fusion success rates at 3, 6, and 12 months, lower VAS score at 6 months, and lower ODI score at 3, 6, and 12 months. The complication rate was similar between graft substitutes with autologous cell therapies and graft substitutes alone. Although the current literature remains limited, this meta-analysis suggests that the incorporation of cellular therapies such as bone marrow and platelet derivatives with graft substitutes is associated with a higher fusion rate and significant improvements in functional status and pain following spinal fusion. Future well-designed randomized clinical trials are needed to definitively assess the clinical effectiveness of cellular therapies in spinal fusion.

Improved Preservation of Rat Small Intestine Transplantation Graft by Introduction of Mesenchymal Stem Cell-Secreted Fractions.

Segmental grafts from living donors have advantages over grafts from deceased donors when used for small intestine transplantation. However, storage time for small intestine grafts can be extremely short and optimal graft preservation conditions for short-term storage remain undetermined. Secreted factors from mesenchymal stem cells (MSCs) that allow direct activation of preserved small intestine grafts. Freshly excised Luc-Tg LEW rat tissues were incubated in preservation solutions containing MSC-conditioned medium (MSC-CM). Preserved Luc-Tg rat-derived grafts were then transplanted to wild-type recipients, after which survival, injury score, and tight junction protein expression were examined. Luminance for each graft was determined using in vivo imaging. The findings indicated that 30-100 and 3-10 kDa fractions of MSC-CM have superior activating effects for small intestine preservation. Expression of the tight-junction proteins claudin-3, and zonula occludens-1 preserved for 24 h in University of Wisconsin (UW) solution containing MSC-CM with 50-100 kDa, as shown by immunostaining, also indicated effectiveness. Reflecting the improved graft preservation, MSC-CM preloading of grafts increased survival rate from 0% to 87%. This is the first report of successful transplantation of small intestine grafts preserved for more than 24 h using a rodent model to evaluate graft preservation conditions that mimic clinical conditions.

[The prognostic value of colonoscopy grading for acute graft-versus-host disease in patients with malignant hematological disorders after unrelated cord blood transplantation].

Objective: To investigate the prognostic value of enteroscopic grading for the prognostic assessment of patients with malignant hematological diseases who developed intestinal acute graft-versus-host disease (IT-aGVHD) after unrelated cord blood transplantation (UCBT) . Methods: Fifty patients with IT-aGVHD who developed hormone resistance after UCBT from June 2016 to June 2023 at Anhui Provincial Hospital were collected to compare the effective and survival rates of IT-aGVHD treatment in the group with milder enteroscopic mucosal injury (27 cases, enteroscopic grading of Ⅰ and Ⅱ) and the group with more severe injury (23 cases, enteroscopic grading of Ⅲ and Ⅳ) and to retrospectively analyze the factors affecting patients' prognosis. Results: Patients in the mild and severe groups had an effective rate of 92.6% and 47.8% at 28 days after colonoscopy (P<0.001), 81.5% and 39.1% at 56 days after colonoscopy (P=0.002), with optimal effective rate of 92.6% and 65.2% (P=0.040), respectively, and the differences were statistically significant. The multifactorial analysis found that enteroscopic grading was an independent risk factor affecting the effective rate of IT-aGVHD treatment. The overall survival rate at 2 years after colonoscopy was 70.4% (95% CI 52.0% -88.8% ) and 34.8% (95% CI 14.8% -54.8% ) for patients in the mild and severe groups, respectively, and the difference was statistically significant (P=0.003). Multifactorial analysis revealed that enteroscopic grading, cytomegalovirus infection status, second-line treatment regimen, and patients' age were independent risk factors for survival. Conclusion: The treatment efficacy and prognosis of patients in the group with less severe enteroscopic injury (grades Ⅰ and Ⅱ) were better than those in the group with more severe injury (grades Ⅲ and Ⅳ) .

Lower eyelid retraction repair using autologous auricular scapha cartilage.

PURPOSE: To assess the efficacy of lower eyelid retraction surgery utilizing autologous auricular scapha cartilage (located within the anterior surface groove between the helix and anti-helix) and to present the surgical outcomes in a patient cohort. METHODS: Medical records of 21 patients who underwent lower eyelid retraction surgery with scapha cartilage were retrospectively reviewed. Retractions, present for an extended duration (6 months to 20 years), exhibited 1 mm or more inferior scleral show, attributed to prior lower eyelid blepharoplasty, facial palsy, or as a normal anatomical variation. Surgical interventions included lateral canthotomy, cantholysis, incision of the subtarsal conjunctiva-lower eyelid retractors, lower eyelid retractor lysis, cartilage graft suturing to the defect area without conjunctival cover, and tightening of the lateral canthal corner in all patients. RESULTS: A total of 29 eyelids in 21 patients underwent surgery without intraoperative complications. Over a mean follow-up period of 11 months (range: 6-30 months), lower lid retraction improved in 96.5% of eyelids. Postoperative margin-to-reflex distance measurements (MRD2) significantly decreased compared to preoperative values (p = 0.001; p < 0.01). Average improvements in MRD2-a (midpupil to lower lid) and MRD2-b (lateral limbus to lower lid) were 1.77 ± 0.80 and 2.04 ± 0.81, respectively (p = 0.001; p < 0.01). Four eyelids (4/29) required revision due to canthal corner loosening, with correction necessitating periosteal flaps. All four patients had previously undergone two or more repairs elsewhere. The graft was visible in two lids but did not require further revision. One patient experienced mild helix deformity at the donor site, which did not warrant additional intervention. CONCLUSION: In cases of lower lid retraction associated with middle/posterior lamellar shortening, utilizing an autologous auricular scapha cartilage spacer graft offers notable benefits. These advantages comprise straightforward harvesting with minimal donor site complications, stability without experiencing shrinkage, a softer texture in comparison to posterior cartilage, a concave shape that facilitates proper fitting on the globe, and its autologous nature.

Anti-thymocyte globulin combined with post-transplantation cyclophosphamide reduce graft-versus-host disease in hematopoietic stem cell transplantation for pediatric leukemia.

This retrospective analysis evaluated the use of anti-thymocyte globulin (ATG) with or without post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prophylaxis in children with acute leukemia undergoing hematopoietic stem cell transplantation (HSCT). The study included 57 children, with 35 in the ATG-PTCy group and 22 in the ATG group. While overall incidence of acute and chronic GvHD did not differ significantly between groups, the ATG-PTCy group had lower rates of grade II-IV acute GvHD (p = 0.013) and moderate-to-severe chronic GvHD (p = 0.001) compared to the ATG group. Importantly, ATG-PTCy significantly improved GvHD/relapse-free survival (GRFS) compared to ATG (65.71% vs. 36.63%; p = 0.003). There were no differences in engraftment, infection rates, immune reconstitution, overall survival, leukemia-free survival, relapse rate, or non-relapse mortality between the two groups. Combining ATG with PTCy may reduce moderate-to-severe GvHD and improve GRFS in children undergoing HSCT for acute leukemia.

Risk of Transfusion in Isolated Coronary Artery Bypass Graft: Models developed from the STS Database.

BACKGROUND: Perioperative blood transfusion is associated with adverse outcomes and higher costs following coronary artery bypass graft surgery (CABG). We developed risk assessments for patients' probability of perioperative transfusion and the expected transfusion volume, to improve clinical management and resource use. METHODS: Among 1,266,545 consecutive (2008-2016) isolated-CABG operations in STS's Adult Cardiac Surgery Database, 657,821 (51.9%) received perioperative blood transfusions (red blood cell [RBC], fresh frozen plasma [FFP], cryoprecipitate, and/or platelets). We developed "full" models to predict perioperative transfusion of any blood product, and of RBC, FFP, or platelets. Using least absolute shrinkage and selection operator model selection, we built a rapid risk score based on 5 variables (age, body surface area, sex, preoperative hematocrit and use of intra-aortic balloon pump). RESULTS: Full model C-statistics were 0.785, 0.815, 0.707, and 0.699 for any blood product, RBC, FFP, and platelets. Rapid risk assessments' C-statistics were 0.752, 0.785, 0.670, and 0.661 for any blood product, RBC, FFP, and platelets. The observed versus expected risk plots showed strong calibration for full models and risk assessment tools; absolute differences between observed and expected risks of transfusion were <10.8% in each percentile of expected risk. Risk-assessments' predicted probabilities of transfusion were strongly and non-linearly associated (p<.0001) with total units transfused. CONCLUSIONS: These robust and well-calibrated risk assessment tools for perioperative transfusion in CABG can inform surgeons regarding patients' risks and number of RBC, FFP, and platelets units they can expect to need. This can aid in optimizing outcomes and increasing efficient use of blood products.

Identification of a subpopulation of highly adherent endothelial cells for seeding synthetic vascular grafts.

OBJECTIVE: There is an unmet clinical need for alternatives to autologous vessel grafts. Small-diameter (<6mm) synthetic vascular grafts are not suitable because of unacceptable patency rates. This mainly occurs due to the lack of an endothelial cell (EC) monolayer to prevent platelet activation, thrombosis, and intimal hyperplasia. There are no reliable methods to endothelialize small-diameter grafts, as most seeded ECs are lost due to exposure to fluid shear stress (SS) after implantation. The goal of this work is to determine if EC loss is a random process or if it is possible to predict which cells are more likely to remain adherent. METHODS: In initial studies, we sorted ECs using fluid SS and identified a subpopulation of ECs that are more likely to resist detachment. We use RNA-sequencing (RNA-seq) to examine gene expression of adherent ECs compared to the whole population. Using fluorescence activated cell sorting (FACS), we sorted ECs based on the expression level of a candidate marker and studied their retention in small-diameter vascular grafts in vitro. RESULTS: Transcriptomic analysis revealed that fibronectin leucine rich transmembrane protein 2 (FLRT2), encoding protein FLRT2, is downregulated in the ECs that are more likely to resist detachment. When seeded onto vascular grafts and exposed to SS, ECs expressing low levels of FLRT2 exhibit 59.2±7.4% retention compared to 24.5±6.1% retention for the remainder of the EC population. CONCLUSIONS: For the first time, we show EC detachment is not an entirely random process. This provides validation for the concept that we can seed small-diameter vascular grafts only with highly adherent ECs to maintain a stable endothelium and improve graft patency rates.

The effect of ADAMTS13 on graft-versus-host disease.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) can potentially cure malignant blood disorders and benign conditions such as haemoglobinopathies and immunologic diseases. However, allo-HSCT is associated with significant complications. The most common and debilitating among them is graft-versus-host disease (GVHD). In GVHD, donor-derived T cells mount an alloimmune response against the recipient. The alloimmune response involves several steps, including recognition of recipient antigens, activation and proliferation of T cells in secondary lymphoid organs, and homing into GVHD-targeted organs. Adhesion molecules on T cells and endothelial cells mediate homing of T cells into lymphoid and non-lymphoid tissues. In this study, we showed that Von Willebrand factor (VWF), an adhesion molecule secreted by activated endothelial cells, plays an important role in mouse models of GVHD. We investigated the effect of the VWF-cleaving protease ADAMTS13 on GVHD. We found that ADAMTS13 reduced the severity of GVHD after bone marrow transplantation from C57BL6 donor to BALB/C recipient mice. A recombinant VWF-A2 domain peptide also reduced GVHD in mice. We showed that ADAMTS13 and recombinant VWF-A2 reduced the binding of T cells to endothelial cells and VWF in vitro, and reduced the number of T cells in lymph nodes, Peyer's patches and GVHD-targeted organs in vivo. We identified LFA-1 (αLß2) as the binding site of VWF on T cells. Our results showed that blocking T-cell homing by ADAMTS13 or VWF-A2 peptide reduced the severity of the GVHD after allo-HSCT, a potentially novel method for treating and preventing GVHD.

Dissection of transcriptional events in graft incompatible reactions of "Bearss" lemon (Citrus limon) and "Valencia" sweet orange (C. sinensis) on a novel citrandarin (C. reticulata × Poncirus trifoliata) rootstock.

Citrus is commercially propagated via grafting, which ensures trees have consistent fruit traits combined with favorable traits from the rootstock such as soil adaptability, vigor, and resistance to soil pathogens. Graft incompatibility can occur when the scion and rootstock are not able to form a permanent, healthy union. Understanding and preventing graft incompatibility is of great importance in the breeding of new fruit cultivars and in the choice of scion and rootstock by growers. The rootstock US-1283, a citrandarin generated from a cross of "Ninkat" mandarin (Citrus reticulata) and "Gotha Road" #6 trifoliate orange (Poncirus trifoliata), was released after years of field evaluation because of its superior productivity and good fruit quality on "Hamlin" sweet orange (C. sinensis) under Florida's growing conditions. Subsequently, it was observed that trees of "Bearss" lemon (C. limon) and "Valencia" sweet orange (C. sinensis) grafted onto US-1283 exhibited unhealthy growth near the graft union. The incompatibility manifested as stem grooving and necrosis underneath the bark on the rootstock side of the graft. Another citrandarin rootstock, US-812 (C. reticulata "Sunki" × P. trifoliata "Benecke"), is fully graft compatible with the same scions. Transcriptome analysis was performed on the vascular tissues above and below the graft union of US-812 and US-1283 graft combinations with "Bearss" and "Valencia" to identify expression networks associated with incompatibility and help understand the processes and potential causes of incompatibility. Transcriptional reprogramming was stronger in the incompatible rootstock than in the grafted scions. Differentially expressed genes (DEGs) in US-1283, but not the scions, were associated with oxidative stress and plant defense, among others, similar to a pathogen-induced immune response localized to the rootstock; however, no pathogen infection was detected. Therefore, it is hypothesized that this response could have been triggered by signaling miscommunications between rootstock and scion either through (1) unknown molecules from the scion that were perceived as danger signals by the rootstock, (2) missing signals from the scion or missing receptors in the rootstock necessary for the formation of a healthy graft union, (3) the overall perception of the scion by the rootstock as non-self, or (4) a combination of the above.

Massive bleeding from an infected pseudoaneurysm in an arteriovenous graft that resulted in death: A case report.

We report an autopsy of a death due to a ruptured infected pseudoaneurysm; a man in his 70s was found dead with massive bleeding from the shunt of his right arm. Autopsy and pathological examination revealed that the cause of death was hemorrhagic shock due to rupture of an infected pseudoaneurysm. Ruptured aneurysms and pseudoaneurysm are a complication of dialysis, and death is rare because they are treated immediately on discovery. However, these ruptures often occur in non-medical facilities and could result in death if the patient does not have knowledge of first aid. Thus, patient education is important. Approximately only half of the deaths due to massive bleeding from a shunt are autopsied. In Japan, autopsies or partial autopsies are considered necessary to determine whether a bleeding was traumatic and to prevent medical errors from being overlooked.

Human placental mesenchymal stromal cells promote the formation of CD8+CD122+PD-1+Tregs via CD73/Foxo1 to alleviate liver injury in graft-versus-host disease mice.

BACKGROUND: Human placental mesenchymal stromal cells (hPMSCs) are known to limit graft-versus-host disease (GVHD). CD8+CD122+PD-1+Tregs have been shown to improve the survival of GVHD mice. However, the regulatory roles of hPMSCs in this subgroup remain unclear. Here, the regulatory mechanism of hPMSCs in reducing liver fibrosis in GVHD mice by promoting CD8+CD122+PD-1+Tregs formation and controlling the balance of IL-6 and IL-10 were explored. METHODS: A GVHD mouse model was constructed using C57BL/6J and BALB/c mice and treated with hPMSCs. LX-2 cells were explored to study the effects of IL-6 and IL-10 on the activation of hepatic stellate cells (HSCs). The percentage of CD8+CD122+PD-1+Tregs and IL-10 secretion were determined using FCM. Changes in hepatic tissue were analysed by HE, Masson, multiple immunohistochemical staining and ELISA, and the effects of IL-6 and IL-10 on LX-2 cells were detected using western blotting. RESULTS: hPMSCs enhanced CD8+CD122+PD-1+Treg formation via the CD73/Foxo1 and promoted IL-10, p53, and MMP-8 levels, but inhibited IL-6, HLF, α-SMA, Col1α1, and Fn levels in the liver of GVHD mice through CD73. Positive and negative correlations of IL-6 and IL-10 between HLF were found in liver tissue, respectively. IL-6 upregulated HLF, α-SMA, and Col1α1 expression via JAK2/STAT3 pathway, whereas IL-10 upregulated p53 and inhibited α-SMA and Col1α1 expression in LX-2 cells by activating STAT3. CONCLUSIONS: hPMSCs promoted CD8+CD122+PD-1+Treg formation and IL-10 secretion but inhibited HSCs activation and α-SMA and Col1α1 expression by CD73, thus controlling the balance of IL-6 and IL-10, and alleviating liver injury in GVHD mice.