PTLD Burkitt Lymphoma in a Patient with Remote Lymphomatoid Granulomatosis.

Posttransplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of solid organ transplantation. The majority of PTLD is of B-cell origin, and 90% are associated with the Epstein-Barr virus (EBV). Lymphomatoid granulomatosis (LG) is a rare, EBV-associated systemic angiodestructive lymphoproliferative disorder, which has rarely been described in patients with renal transplantation. We report the case of a patient with renal transplantation for SLE, who presented, 9 months after renal transplantation, an EBV-associated LG limited to the intracranial structures that recovered completely after adjustment of her immunosuppressive treatment. Nine years later, she developed a second PTLD disorder with central nervous system initial manifestation. Workup revealed an EBV-positive PTLD Burkitt lymphoma, widely disseminated in most organs. In summary, the reported patient presented two lymphoproliferative disorders (LG and Burkitt's lymphoma), both with initial neurological manifestation, at 9 years interval. With careful reduction of the immunosuppression after the first manifestation and with the use of chemotherapy combined with radiotherapy after the second manifestation, our patient showed complete disappearance of neurologic symptoms and she is clinically well with good kidney function. No recurrence has been observed by radiological imaging until now

On a stochastic partial differential equation with non-local diffusion

In this paper, we prove existence, uniqueness and regularity for a class of stochastic partial differential equations with a fractional Laplacian driven by a space-time white noise in dimension one. The equation we consider may also include a reaction term

Meningeal Relapse of Nodular Lymphocyte Predominant Hodgkin Lymphoma Transformed to T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: A Case Report.

Central nervous system involvement in Hodgkin lymphoma is extremely rare, especially in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), which usually carries a favorable prognosis. Here we report a case of a young patient with NLPHL, who developed a progressive and fatal neurological deterioration requiring a very extensive work-up including two biopsies to obtain the diagnosis of T-cell/histiocyte-rich large B-cell lymphoma like transformation. This report, which includes post-mortem analysis, highlights the correlations between clinical, radiological, and biological data but also the difficulties encountered in reaching the correct diagnosis

Fatigue in newly diagnosed acute myeloid leukaemia: General population comparison and predictive factors

Objectives: This study compared the burden of fatigue between treatment-naïve patients with newly diagnosed acute myeloid leukaemia (AML) and the general population and investigated patient factors associated with fatigue severity. Methods: Pretreatment patient-reported fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire in a sample of 463 newly diagnosed patients with AML who were enrolled in a clinical trial. Multivariable linear regression models were used to estimate the adjusted mean differences in fatigue between patients with AML and adults from the general population (n=847) by AML disease risk categories. A clinically meaningful difference in fatigue was defined as ≥3 points. Univariable and multivariable linear regression models were used to identify sociodemographic, clinical and molecular correlates of worse fatigue in patients with AML. Results: Patients with AML reported adjusted mean fatigue scores that were 7.5 points worse than the general population (95% CI -8.6 to -6.4, p<0.001). Across AML disease risk categories, adjusted mean differences in fatigue compared with the general population ranged from 6.7 points worse (patients with favourable risk: 95% CI -8.6 to -4.8, p<0.001) to 8.9 points worse (patients with poor risk, 95% CI -10.5 to -7.2, p<0.001). Overall, 91% of patients with AML reported fatigue that was equal to or worse than the general population's median fatigue score. Higher pretreatment fatigue was independently associated with female sex, WHO performance status ≥1 and lower platelet levels. Conclusions: Patients with newly diagnosed AML reported worse fatigue than the general population, and mean differences exceeded twice the threshold for clinical significance. Our findings may help to identify patients with AML most likely to benefit from supportive care interventions to reduce fatigue

Fatigue in newly diagnosed acute myeloid leukaemia: General population comparison and predictive factors

Objectives: This study compared the burden of fatigue between treatment-naïve patients with newly diagnosed acute myeloid leukaemia (AML) and the general population and investigated patient factors associated with fatigue severity. Methods: Pretreatment patient-reported fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire in a sample of 463 newly diagnosed patients with AML who were enrolled in a clinical trial. Multivariable linear regression models were used to estimate the adjusted mean differences in fatigue between patients with AML and adults from the general population (n=847) by AML disease risk categories. A clinically meaningful difference in fatigue was defined as ≥3 points. Univariable and multivariable linear regression models were used to identify sociodemographic, clinical and molecular correlates of worse fatigue in patients with AML. Results: Patients with AML reported adjusted mean fatigue scores that were 7.5 points worse than the general population (95% CI -8.6 to -6.4, p<0.001). Across AML disease risk categories, adjusted mean differences in fatigue compared with the general population ranged from 6.7 points worse (patients with favourable risk: 95% CI -8.6 to -4.8, p<0.001) to 8.9 points worse (patients with poor risk, 95% CI -10.5 to -7.2, p<0.001). Overall, 91% of patients with AML reported fatigue that was equal to or worse than the general population's median fatigue score. Higher pretreatment fatigue was independently associated with female sex, WHO performance status ≥1 and lower platelet levels. Conclusions: Patients with newly diagnosed AML reported worse fatigue than the general population, and mean differences exceeded twice the threshold for clinical significance. Our findings may help to identify patients with AML most likely to benefit from supportive care interventions to reduce fatigue

MicroRNA signature from extracellular vesicles of HCV/HIV co-infected individuals differs from HCV mono-infected

Hepatitis C virus (HCV) coinfection with human immunodeficiency virus (HIV) has a detrimental impact on disease progression. Increasing evidence points to extracellular vesicles (EVs) as important players of the host-viral cross-talk. The microRNAs (miRNAs), as essential components of EVs cargo, are key regulators of normal cellular processes and also promote viral replication, viral pathogenesis, and disease progression. We aimed to characterize the plasma-derived EVs miRNA signature of chronic HCV infected and HIV coinfected patients to unravel the molecular mechanisms of coinfection. EVs were purified and characterized from 50 plasma samples (21 HCV mono- and 29 HCV/HIV co-infected). EV-derived small RNAs were isolated and analyzed by massive sequencing. Known and de novo miRNAs were identified with miRDeep2. Significant differentially expressed (SDE) miRNA identification was performed with generalized linear models and their putative dysregulated biological pathways were evaluated. Study groups were similar for most clinical and epidemiological characteristics. No differences were observed in EVs size or concentration between groups. Therefore, HCV/HIV co-infection condition did not affect the concentration or size of EVs but produced a disturbance in plasma-derived EVs miRNA cargo. Thus, a total of 149 miRNAs were identified (143 known and 6 de novo) leading to 37 SDE miRNAs of which 15 were upregulated and 22 downregulated in HCV/HIV co-infected patients. SDE miRNAs regulate genes involved in inflammation, fibrosis, and cancer, modulating different biological pathways related to HCV and HIV pathogenesis. These findings may help to develop new generation biomarkers and treatment strategies, in addition to elucidate the mechanisms underlying virus-host interaction. KEY MESSAGES: HCV and HCV/HIV displayed similar plasma-EV size and concentration. EVs- derived miRNA profile was characterized by NGS. 37 SDE miRNAs between HCV and HCV/HIV were observed. SDE miRNAs regulate genes involved in inflammation, fibrosis and cancer.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work has been supported by grants from (1) Institute of Health Carlos III, Spain [PI18CIII/00020/ to AFR], (2) PID2021–126781OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”, (3) The SPANISH AIDS Research Network RD16CIII/0002/0002 - ISCIII – FEDER, (4) Centro de Investigación en Red en Enfermedades Infecciosas (CIBERINFEC) CB21/13/00044, (5) the National Agency for Scientific and Technology Promotion (ANPCyT) (PICT 2017 Nº713), and (6) the National Research Council (CONICET, PIP 2021-2023). V.C. received funding form the Asociación Universitaria Iberoamericana de Postgrado (AUIP) for the Academic Mobility Scholarship Program. P.V., E.D.M., and M.V.P. are members of the CONICET-Research Career Program. V.C. is a fellow from ANPCyT. The funder’s had no role in the study design, data collection and analysis, decision to publish, or the preparation of the manuscript.S

Multidimensional Results and Reflections on CAR-T: The Italian Evidence

The present study aims at defining the economic and organizational impacts of the introduction of chimeric antigen receptor T-cell therapy (CAR-T) in Italy, for the management of diffuse large B-cell lymphoma (DLBCL) patients in third-line therapy, defining the overall level of sustainability for both hospitals and the National Healthcare System (NHS). The analysis focused on CAR-T and Best Salvage Care (in the following BSC), assuming the Italian hospital and NHS perspectives, over a 36-month time horizon. Process mapping and activity-based costing methodologies were applied to collect the hospital costs related to the BSC and CAR-T pathways, including adverse event management. Anonymous administrative data on services provided (diagnostic and laboratory examinations, hospitalizations, outpatient procedures, and therapies) to 47 third-line patients with lymphoma, as well as any organizational investments required, were collected, in two different Italian Hospitals. The economic results showed that the BSC clinical pathway required less resources in comparison with CAR-T (excluding the cost related to the therapy) (BSC: 29,558.41 vs. CAR-T: EUR 71,220.84, −58.5%). The budget impact analysis depicts that the introduction of CAR-T would generate an increase in costs ranging from 15% to 23%, without considering treatment costs. The assessment of the organizational impact reveals that the introduction of CAR-T therapy would require additional investments equal to a minimum of EUR 15,500 to a maximum of EUR 100,897.49, from the hospital perspective. Results show new economic evidence for healthcare decision makers, to optimize the appropriateness of resource allocation. The present analysis suggests the need to introduce a specific reimbursement tariff, both at the hospital and at NHS levels, since no consensus exists, at least in the Italian setting, concerning the proper remuneration for the hospitals who guarantee this innovative pathway, assuming high risks related to timely management of adverse events

Prevalence of subclinical contributors to low bone mineral density and/or fragility fracture

Objective: The prevalence of subclinical contributors to low bone mineral density (BMD) and/or fragility fracture is debated. We evaluated the prevalence of subclinical contributors to low BMD and/or fragility fracture in the presence of normal 25-hydroxyvitamin D (25OHVitD) levels. Design: Prospective observational study. Methods: Among 1095 consecutive outpatients evaluated for low BMD and/or fragility fractures, 602 (563 females, age 65.4G10.0 years) with apparent primary osteoporosis were enrolled. A general chemistry profile, phosphate, 25OHVitD, cortisol after 1-mg overnight dexamethasone suppression test, antitissue transglutaminase and endomysial antibodies and testosterone (in males) were performed. Serum and urinary calcium and parathyroid hormone levels were also evaluated after 25OHVitD levels normalization. Vertebral deformities were assessed by radiograph. Results: In total, 70.8% of patients had low 25OHVitD levels. Additional subclinical contributors to low BMD and/or fragility fracture were diagnosed in 45% of patients, with idiopathic hypercalciuria (IH, 34.1%) and primary hyperparathyroidism (PHPT, 4.5%) being the most frequent contributors, apart from hypovitaminosis D. Furthermore, 33.2% of IH and 18.5% of PHPT patients were diagnosed only after 25OHVitD levels normalization. The subclinical contributors to low BMD and/or fragility fracture besides hypovitaminosis D were associated inversely with age (odds ratio (OR) 1.02, 95% CI 1-1.04, PZ0.04) and BMI (OR 1.1, 95% CI 1.05-1.17, PZ0.0001) and directly with fragility fractures (OR 1.89, 95% CI 1.31-2.73, PZ0.001), regardless of BMD. Conclusions: Subclinical contributors to low BMD and/or fragility fracture besides hypovitaminosis D are present in more than 40% of the subjects with apparent primary osteoporosis. Hypovitaminosis D masks a substantial proportion of IH and PHPT patients

Prognostic impact of KMT2A-AFF1-positivity in 926 BCR-ABL1-negative B-lineage acute lymphoblastic leukemia patients treated in GIMEMA clinical trials since 1996

The impact of KMT2A-AFF1 rearrangement in pediatric-like, minimal residual disease (MRD)-based clinical trials and the effect of transplant in KMT2A-AFF1 ALL are still debated

ELN2017 risk stratification improves outcome prediction when applied to the prospective GIMEMA AML1310 protocol

The 2017 version of the European LeukemiaNet (ELN) recommendations, by integrating cytogenetics and mutational status of specific genes, divides patients with acute myeloid leukemia into 3 prognostically distinct risk categories: favorable (ELN2017-FR), intermediate (ELN2017-IR), and adverse (ELN2017-AR). We performed a post hoc analysis of the GIMEMA (Gruppo Italiano Malattie EMatologiche dell’Adulto) AML1310 trial to investigate the applicability of the ELN2017 risk stratification to our study population. In this trial, after induction and consolidation, patients in complete remission were to receive an autologous stem cell transplant (auto-SCT) if categorized as favorable risk or an allogeneic stem cell transplant (allo-SCT) if adverse risk. Intermediate-risk patients were to receive auto-SCT or allo-SCT based on the postconsolidation levels of measurable residual disease as measured by using flow cytometry. Risk categorization was originally conducted according to the 2009 National Comprehensive Cancer Network recommendations. Among 500 patients, 445 (89%) were reclassified according to the ELN2017 criteria: ELN2017-FR, 186 (41.8%) of 455; ELN2017-IR, 179 (40.2%) of 445; and ELN2017-AR, 80 (18%) of 455. In 55 patients (11%), ELN2017 was not applicable. Two-year overall survival (OS) was 68.8%, 51.3%, 45.8%, and 42.8% for the ELN2017-FR, ELN2017-IR, ELN2017-not classifiable, and ELN2017-AR groups, respectively (P, .001). When comparing the 2 different transplant strategies in each ELN2017 risk category, a significant benefit of auto-SCT over allo-SCT was observed among ELN2017-FR patients (2-year OS of 83.3% vs 66.7%; P 5 .0421). The 2 transplant procedures performed almost equally in the ELN2017-IR group (2-year OS of 73.9% vs 70.8%; P 5 .5552). This post hoc analysis of the GIMEMA AML1310 trial confirms that the ELN2017 classification is able to accurately discriminate patients with different outcomes and who may benefit from different transplant strategies. This trial was registered as EudraCT number 2010-023809-36 and at www.clinicaltrials.gov as #NCT01452646