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Purpose. There have been many studies in the operative management of pyogenic spondylodiscitis with foreign materials. However, it still remains an issue of debate on whether the allografts may be used in pyogenic spondylodiscitis. This study sought to evaluate the safety and effectiveness of PEEK cages and the cadaveric allograft in transforaminal lumbar interbody fusion (TLIF) for treating lumbar pyogenic spondylodiscitis. Methods. From January 2012 to December 2019, 56 patients underwent surgery for lumbar pyogenic spondylodiscitis. The posterior debridement of all patients and their fusion with allografts, local bone grafts, and bone chip cages were performed before posterior pedicle screw fusion. An assessment of the residual pain, the grade of neurological injury, and the resolution of infection was conducted on 39 patients. The clinical outcome was evaluated using a visual analog scale (VAS) and the Oswestry Disability Index (ODI), and neurological outcomes were appraised based on Frankel grades. The radiological outcomes were evaluated via focal lordosis, lumbar lordosis, and the state of the fusion. Results. Staphylococcus aureus and Staphylococcus epidermidis were the most common causative organisms. The mean preoperative focal lordosis was -1.2° (-11.4° to 5.7°), and the mean postoperative focal lordosis increased to 10.3° (4.3°-17.2°). At the final follow-up, there were five cases with subsidence of the cage, no case of recurrence, and no case with cage and screw loosening or migration. The mean preoperative VAS and ODI scores were 8.9 and 74.6%, respectively, and improvements in VAS and ODI were 6.6±2.2 and 50.4±21.3%, respectively. The Frankel grade D was found in 10 patients and grade C in 7. Following the final follow-up, only one patient improved from Frankel grade C to grade D while the others recovered completely. Conclusion. The PEEK cage and cadaveric allograft combined with local bone grafts is a safe and effective choice for intervertebral fusion and restoring sagittal alignment without increased incidence of relapse for treating lumbar pyogenic spondylodiscitis.

Mechanisms that mediate allograft tolerance differ between organs. We have previously shown that [Foxp3.sup.+] T cell-enriched bronchus-associated lymphoid tissue (BALT) is induced in tolerant murine lung allografts and that these [Foxp3.sup.+] cells suppress alloimmune responses locally and systemically. Here, we demonstrated that [Foxp3.sup.+] cells that reside in tolerant lung allografts differed phenotypically and transcriptionally from those in the periphery and were clonally expanded. Using a mouse lung retransplant model, we showed that recipient [Foxp3.sup.+] cells were continuously recruited to the BALT within tolerant allografts. We identified distinguishing features of graft-resident and newly recruited [Foxp3.sup.+] cells and showed that graft-infiltrating [Foxp3.sup.+] cells acquired transcriptional profiles resembling those of graft- resident [Foxp3.sup.+] cells over time. Allografts underwent combined antibody-mediated rejection and acute cellular rejection when recruitment of recipient [Foxp3.sup.+] cells was prevented. Finally, we showed that local administration of IL-33 could expand and activate allograft-resident [Foxp3.sup.+] cells, providing a platform for the design of tolerogenic therapies for lung transplant recipients. Our findings establish graft- resident [Foxp3.sup.+] cells as critical orchestrators of lung transplant tolerance and highlight the need to develop lung-specific immunosuppression.

To compare the effects of corneal allogenic intrastromal ring segment (CAIRS) implantation on topographical measurements and visual outcomes of patients with keratoconus with and without corneal cross-linking (CXL) prior to the time of implantation. Sixty-seven eyes with corneal allograft intrastromal ring segment implantation (KeraNatural; Lions VisionGift) due to advanced keratoconus were included in the study. Thirty-seven eyes had no CXL and 30 eyes had had CXL before being referred to the authors. The changes in spherical equivalent (SE), uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), steep keratometry (K1), flat keratometry (K2), mean keratometry (Kmean), maximum keratometry (Kmax), and thinnest pachymetry were retrospectively analyzed 6 months after the implantation. The median age was 29 years in the CXL group and 24.0 years in the non-CXL group (P >.05), respectively. All topographical and visual parameters before implantation were similar in both groups (P >.05 for all parameters). At 6 months, CDVA, K1, and Kmean showed higher improvement in the non-CXL group than the CXL group (P =.030,.018, and.039, respectively). CAIRS surgery has a flattening effect on both the corneas with and without CXL. The cornea with prior CXL treatment had less flattening effect due to the stiffening effect of prior CXL.

Cancer-specific inhibitors that reflect the unique metabolic needs of cancer cells are rare. Here we describe Gboxin, a small molecule that specifically inhibits the growth of primary mouse and human glioblastoma cells but not that of mouse embryonic fibroblasts or neonatal astrocytes. Gboxin rapidly and irreversibly compromises oxygen consumption in glioblastoma cells. Gboxin relies on its positive charge to associate with mitochondrial oxidative phosphorylation complexes in a manner that is dependent on the proton gradient of the inner mitochondrial membrane, and it inhibits the activity of F 0 F 1 ATP synthase. Gboxin-resistant cells require a functional mitochondrial permeability transition pore that regulates pH and thus impedes the accumulation of Gboxin in the mitochondrial matrix. Administration of a metabolically stable Gboxin analogue inhibits glioblastoma allografts and patient-derived xenografts. Gboxin toxicity extends to established human cancer cell lines of diverse organ origin, and shows that the increased proton gradient and pH in cancer cell mitochondria is a mode of action that can be targeted in the development of antitumour reagents. Gboxin and its chemical derivatives inhibit the growth of primary human and mouse glioblastoma cells, but not of mouse embryonic fibroblasts or neonatal astrocytes, by targeting mitochondrial oxidative phosphorylation complexes.

Hematopoietic cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants done in Europe and associated countries continues to rise with 45,418 HCT in 41,100 patients [(17,155 allogeneic (42%) and 23,945 autologous (58%)] reported by 683 centers in 50 countries in 2017. Main indications were myeloid malignancies 10,147 (25%; 96% allogeneic), lymphoid malignancies 26,488 (64%; 19% allogeneic), solid tumors 1,607 (3.9%; 2% allogeneic), and nonmalignant disorders 2,667 (7%; 81% allogeneic). Trends in donor choice seen before continue, with growing numbers of haploidentical HCT and decreasing use of cord blood. Of interest is that after many years of continued growth, the number of patients receiving an allogeneic HCT for marrow failure is decreasing slightly (p < 0.001). Such a change may be explained by the use of thrombopoietin analogs in aplastic anemia patients. Other nonmalignant indications, however continue to grow, most importantly HCT for hemoglobinopathies by 36%, equally for thalassemias and sickle cell disease. Non-HCT cell therapies have increased by 28% since 2015 and genetically modified T cells is type of cell therapy with the fastest growth. These annual reports reflect current activity and trends and are useful for health-care planning.

Background: The aim of this study was to evaluate the effectiveness of positron emission tomography/computed tomography with [[sup.18] F]-fludeoxyglucose (FDG-PET/CT) and radiomics analysis in detecting differences between the native aorta and the abdominal aortic allograft after the total eradication of infection in patients undergoing infected graft removal and in situ reconstruction with cryopreserved allografts. Methods: Between January 2008 and December 2018, 56 vascular reconstructions with allografts have been performed at our department. The present series included 12 patients undergoing abdominal aortic in situ reconstruction with cryopreserved allografts. During the follow-up, all patients underwent a total-body [[sup.18] F]FDG PET/CT with subsequent radiomics analysis. In all patients, a comparative analysis between the data extracted from native aorta and cryopreserved graft for each patient was performed. Results: All patients were male with a mean age of 72.8 years (range 63–84). Mean duration of follow-up was 51.3 months (range 3–120). During the follow-up, 2 patients (16.7%) needed a redo allograft-related surgical intervention. Overall, the rate of allograft dilatation was 33.3%. No patient had a redo infection during the follow-up. Radiomics analysis showed a different signature of implanted allograft and native aorta. Comparative analysis between the native aortas and cryopreserved allografts (dilated or not) showed several statistical differences for many texture features. Conclusions: The higher metabolic activity of allografts could indicate a state of immune-mediated degeneration. This theory should be proven with prospective, multicentric studies with larger sample sizes.

Background Autogenous bone graft is the gold standard bone graft material. However, due to limitations of supply and morbidity associated with autograft harvest, various bone substitutes have been considered. This article aims to review the properties of the bone graft and various bone substitutes currently available in orthopedic surgery. Main body Synthetic bone substitutes consist of hydroxyapatite, tricalcium phosphate, calcium sulfate, or a combination of these minerals. Synthetic porous substitutes share several advantages over allografts, including unlimited supply, easy sterilization, and storage. However, they also have some disadvantages, such as brittle properties, variable rates of resorption, and poor performance in some clinical conditions. Recently, attention has been drawn to osteoinductive materials, such as demineralized bone matrix and bone morphogenetic proteins. Conclusion Despite tremendous efforts toward developing autograft alternatives, a single ideal bone graft substitute has not been developed. The surgeon should understand the properties of each bone graft substitute to facilitate appropriate selection in each specific clinical situation.

Donor-specific (d-sp) interferon gamma enzyme-linked immunosorbent spot (d-sp ELISPOT) and Panel of reactive T-cell (PRT) ELISPOT assays have been developed to detect alloreactive memory T (Tmem) cells in order to estimate the risk of acute rejection after kidney transplantation. Adding IL15 to the PRT assay (PRT+IL15) may uncover the presence of pathogenic alloreactive CD28.sup.- Tmem. Face-to-face comparisons of these assays have not been done yet. We performed pre-transplant d-sp ELISPOT and PRT assays (±IL15, against six B-cell lines) in 168 consecutive kidney transplant recipients and evaluated the multivariable-adjusted associations with biopsy-proven acute rejection (BPAR), de novo donor-specific antibodies (DSA), and eGFR decline over a 48-month follow-up period. D-sp ELISPOT was positive in 81 (48%) subjects, while 71 (42%) and 81 (48%) subjects displayed positive PRT and PRT+IL15, respectively. Their median [interquartile range] numerical test result was 23 [6-65], 18 [8-37], and 26 [10-45] spots/3x10.sup.5 PBMCs, respectively. The number of PRT spots were weakly correlated with those of d-sp ELISPOT, but highly correlated with PRT+IL15 (rho = 0.96, P<0.001). d-sp ELISPOT, but not PRT (±IL15) was independently associated with BPAR (adjusted Odds Ratio of BPAR associated with d-sp ELISPOT positivity: 4.20 [95%CI: 1.06 to 21.73; P = 0.041]). Unlike d-sp ELISPOT, median PRT and PRT+IL15 were independently associated with higher [DELTA]3-48month eGFR decline post-transplantation (for both assays, about -3mL/min/1.73m2 per one standard deviation unit increase in the spot number). Pre-transplant T-cell immune-monitoring using d-sp ELISPOT and PRT assays identifies kidney transplant candidates at high risk of BPAR and worse kidney allograft progression.

T cell Ig domain and mucin domain protein 1 (TIM-1) is a costimulatory molecule that regulates immune responses by modulating CD4+ T cell effector differentiation. However, the function of TIM-1 on other immune cell populations is unknown. Here, we show that in vivo in mice, TIM-1 is predominantly expressed on B rather than T cells. Importantly, TIM-1 was expressed by a large majority of IL-10-expressing regulatory B cells in all major B cell subpopulations, including transitional, marginal zone, and follicular B cells, as well as the B cell population characterized as CD1d(hi)CD5+. A low-affinity TIM-1-specific antibody that normally promotes tolerance in mice, actually accelerated (T cell-mediated) immune responsiveness in the absence of B cells. TIM-1+ B cells were highly enriched for IL-4 and IL-10 expression, promoted Th2 responses, and could directly transfer allograft tolerance. Both cytokine expression and number of TIM-1+ regulatory B cells (Bregs) were induced by TIM-1-specific antibody, and this was dependent on IL-4 signaling. Thus, TIM-1 is an inclusive marker for IL-10+ Bregs that can be induced by TIM-1 ligation. These findings suggest that TIM-1 may be a novel therapeutic target for modulating the immune response and provide insight into the signals involved in the generation and induction of Bregs.