84 research outputs found
New polymeric sorbent for the solid-phase extraction of indole-3-acetic acid from plants followed by liquid chromatography — Fluorescence detector
Discovering Genotype Variants in an Infant with VACTERL through Clinical Exome Sequencing: A Support for Personalized Risk Assessment and Disease Prevention
Abstract: Congenital anomalies may have an increased risk of noncommunicable diseases (NCDs)
We performed a clinical exome analysis in an infant affected by “Vertebral, Anorectal, Cardiac,
Tracheoesophageal, Genitourinary, and Limb” (VACTERL) malformation association to identify
potential biomarkers that may be helpful for preventing malignancy risk or other chronic processes.
Among the variants, six variants that may be linked with VACTERL were identified in the exome
analysis. The variants c.501G>C on OLR1 and c.-8C>G on PSMA6 were previously associated with
myocardial infarction. The variants c.1936A>G on AKAP10 and c.575A>G on PON1 are linked to
defects in cardiac conduction and artery disease, respectively. Alterations in metabolism were also
suggested by the variants c.860G>A on EPHX2 and c.214C>A on GHRL. In addition, three variants
associated with colon cancer were discovered. Specifically, the reported variants were c.723G>A
on CCND1 and c.91T>A on AURKA proto-oncogenes as well as c.827A>C in the tumor suppressor
PTPRJ. A further inspection identified 15 rare variants carried by cancer genes. Specifically, these
mutations are located on five tumor suppressors (SDHA, RB1CC1, PTCH1, DMBT1, BCR) and eight
proto-oncogenes (MERTK, CSF1R, MYB, ROS1, PCM1, FGFR2, MYH11, BRCC3) and have an allele
frequency lower than 0.01 in the Genome Aggregation Database (GnomAD).We observed that the
cardiac and metabolic phenotypic traits are linked with the genotype of the patient. In addition, the
risk of developing neoplasia cannot be excluded a priori. Long-term surgical issues of patients with
VATER syndrome could benefit from the clinical exome sequencing of a personalized risk assessment
for the appearance of further disease in pubertal timing and adult age
Donor-Specific Anti-HLA Antibodies in Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide: Risk of Graft Failure, Poor Graft Function, and Impact on Outcomes.
The presence of donor-specific anti-HLA antibodies (DSA) is associated with a 10-fold increased risk of graft failure in haploidentical stem cell transplantation (haplo-SCT). Consensus guidelines from the European Society for Blood and Marrow Transplantation set a mean fluorescence intensity (MFI)1000 as a cutoff for DSA positivity. In the absence of an alternative donor, it is recommended that patients undergo desensitization therapy, especially with high DSA levels (5000 MFI). The aim of this study was to analyze the impact of DSA on risk of graft failure and poor graft function, as well as on major outcomes in a consecutive cohort of patients who were systematically screened for DSA before haplo-SCT. A total of 141 consecutive patients were candidates for unmanipulated haplo-SCT with post-transplantation cyclophosphamide (PT-Cy) at our center between January 2012 and January 2018, and 135 were analyzed for the presence of HLA antibodies. Of these 134 patients underwent haplo-SCT. HLA antibodies were detected in 40 patients, including 19 with DSA and 21 without DSA. Ten of the 19 patients with DSA underwent transplantation using that donor, whereas 2 underwent a desensitization program before transplantation. Only 2 patients experienced primary graft failure (1.4 %), both of whom were without DSA. Twenty patients developed a poor graft function (15%). The 3-year overall survival (OS), 3-year progression-free survival (PFS), and 1-year nonrelapse mortality (NRM) were analyzed according to the presence or absence of DSA. No statistically significant difference was found. No impact of the presence of DSA on the risk of developing graft failure and poor graft function was revealed. Major outcomes of transplantation were analyzed separately in patients with poor graft function and those with good graft function. The 3-year OS, 3-year PFS, and 1-year NRM in good graft function and poor graft function populations were 62% versus 20% (P.0001), 53% versus 20% (P.0001), and 12% versus 40% (P = .009), respectively. The presence of low-level DSA in the absence of desensitization did not correlate with the risk of developing graft failure and poor graft function. Patients who experienced poor graft function had worse outcomes than patients with good graft function
Indole-3-acetic acid in plant-pathogen interactions: a key molecule for in planta bacterial virulence and fitness
AN INTEGRATED MODEL SYSTEM TO INVESTIGATE THE EFFECT OF COPPER ON PLANT PATHOGEN INTERACTION.
Allogeneic Stem Cell Transplantation Compared with Chemotherapy for Poor-Risk Hodgkin Lymphoma
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Peripheral Blood Hemopoietic Stem Cell Mobilization Regimens in POEMS Syndrome: A Retrospective Study at 2 Hematologic Italian Centers.
ABSTRACT Autologous peripheral blood stem cell transplantation should be considered first-line therapy in young patients with POEMS. The best protocol to collect peripheral blood stem cells remains to be defined, because of the disease rarity and the heterogeneity of published case series. We collected clinical and laboratory data from 25 patients undergoing mobilization, of whom 11 were mobilized using cyclophosphamide (CY) followed by granulocyte colony-stimulating factor (G-CSF) and 14 patients using G-CSF. The incidence of poor mobilization was low and not statistically different between the 2 groups. Both schemes (CY plus G-CSF versus G-CSF alone) were able to harvest a sufficient CD34+ cell dose
Evaluation of plan complexity and dosimetric plan quality of total marrow and lymphoid irradiation using volumetric modulated arc therapy
PurposeTo assess the impact of the planner's experience and optimization algorithm on the plan quality and complexity of total marrow and lymphoid irradiation (TMLI) delivered by means of volumetric modulated arc therapy (VMAT) over 2010-2022 at our institute. MethodsEighty-two consecutive TMLI plans were considered. Three complexity indices were computed to characterize the plans in terms of leaf gap size, irregularity of beam apertures, and modulation complexity. Dosimetric points of the target volume (D2%) and organs at risk (OAR) (Dmean) were automatically extracted to combine them with plan complexity and obtain a global quality score (GQS). The analysis was stratified based on the different optimization algorithms used over the years, including a knowledge-based (KB) model. Patient-specific quality assurance (QA) using Portal Dosimetry was performed retrospectively, and the gamma agreement index (GAI) was investigated in conjunction with plan complexity. ResultsPlan complexity significantly reduced over the years (r = -0.50, p < 0.01). Significant differences in plan complexity and plan dosimetric quality among the different algorithms were observed. Moreover, the KB model allowed to achieve significantly better dosimetric results to the OARs. The plan quality remained similar or even improved during the years and when moving to a newer algorithm, with GQS increasing from 0.019 +/- 0.002 to 0.025 +/- 0.003 (p < 0.01). The significant correlation between GQS and time (r = 0.33, p = 0.01) indicated that the planner's experience was relevant to improve the plan quality of TMLI plans. Significant correlations between the GAI and the complexity metrics (r = -0.71, p < 0.01) were also found. ConclusionBoth the planner's experience and algorithm version are crucial to achieve an optimal plan quality in TMLI plans. Thus, the impact of the optimization algorithm should be carefully evaluated when a new algorithm is introduced and in system upgrades. Knowledge-based strategies can be useful to increase standardization and improve plan quality of TMLI treatments
Automatic planning of the lower extremities for total marrow irradiation using volumetric modulated arc therapy
Purpose Total marrow (and lymphoid) irradiation (TMI-TMLI) is limited by the couch travel range of modern linacs, which forces the treatment delivery to be split into two plans with opposite orientations: a head-first supine upper-body plan, and a feet-first supine lower extremities plan. A specific field junction is thus needed to obtain adequate target coverage in the overlap region of the two plans. In this study, an automatic procedure was developed for field junction creation and lower extremities plan optimization. Methods Ten patients treated with TMI-TMLI at our institution were selected retrospectively. The planning of the lower extremities was performed automatically. Target volume parameters (CTV_J-V-98% > 98%) at the junction region and several dose statistics (D-98%, D-mean, and D-2%) were compared between automatic and manual plans. The modulation complexity score (MCS) was used to assess plan complexity. Results The automatic procedure required 60-90 min, depending on the case. All automatic plans achieved clinically acceptable dosimetric results (CTV_J-V-98% > 98%), with significant differences found at the junction region, where D-mean and D-2% increased on average by 2.4% (p < 0.03) and 3.0% (p < 0.02), respectively. Similar plan complexity was observed (median MCS = 0.12). Since March 2022, the automatic procedure has been introduced in our clinic, reducing the TMI-TMLI simulation-to-delivery schedule by 2 days. Conclusion The developed procedure allowed treatment planning of TMI-TMLI to be streamlined, increasing efficiency and standardization, preventing human errors, while maintaining the dosimetric plan quality and complexity of manual plans. Automated strategies can simplify the future adoption and clinical implementation of TMI-TMLI treatments in new centers
Peripheral Blood Stem Cells versus Bone Marrow for T Cell-Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide in Hodgkin Lymphoma.
Abstract Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) represents a potential curative strategy for patients with Hodgkin lymphoma (HL) when a matched related or unrelated donor is not available. The role of graft source, either bone marrow (BM) or peripheral blood stem cells (PBSCs), in this setting has not been fully elucidated. We performed a retrospective study on 91 patients with HL to compare the outcome after BM (n = 53) or PBSC (n = 38) transplant. Eighty-nine patients engrafted with no difference between BM and PBSCs in terms of median time for neutrophil (20 versus 20 days, P = .405) and platelet (26 versus 26.5 days, P = .994) engraftment. With a median follow-up of 40.2 months, 100-day cumulative incidences of grades II to IV acute graft-versus host disease (GVHD) and grades II to IV acute GVHD were 24% and 4%, respectively. Graft source was not associated with a different risk of acute GVHD both by univariate and multivariate analyses. Consistently, 1-year cumulative incidence of chronic GVHD was 7% with no differences between the 2 graft types (P = .761). Two-year rates of overall survival (OS), progression-free survival (PFS), nonrelapse mortality, and GVHD/relapse-free survival (GRFS) were 67%, 58%, 20%, and 52%, respectively. By univariate analysis, pretransplant disease status was the main variable affecting all outcomes. By multivariate analysis, PBSCs resulted in a protective factor for OS (hazard ratio [HR], .29; P = .006), PFS (HR, .38; P = .001), and GRFS (HR, .44; P = .020). The other independent variables affecting the final outcome were pretransplant disease status and hematopoietic cell transplant–specific comorbidity index. In conclusion, when planning a haplo-SCT with PT-Cy for patients with poor-risk HL, graft type is an important variable to take into account when selecting the best available donor
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