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We evaluated the incidence of GVHD, risk factors and the impact of graft composition on acute GVHD (aGVHD) in 92 children who underwent BMT for thalassemia following busulfan/cyclophosphamide (BUCY)-based conditioning regimens and GVHD prophylaxis with CSA/short-MTX and methylprednisolone. The incidence of grade 2-4 and 3-4 aGVHD was 35% (95% confidence interval (CI) 25-44) and 9% (95% CI 4-16), respectively. We found that CD3+ and CD34+ cell doses above the median were associated with high incidence of grade 2-4 aGVHD (49 vs 20%, P=0.005 and 46 vs 23%, P=0.021, respectively). In multivariate analysis, high CD3+ (hazard ratio (HR) 4.6; 95% CI 1.4-14.7; P=0.010) and CD34+ (HR 4.3; 95% CI 1.4-12.7; P=0.011) cell doses were associated with grade 2-4 aGVHD. We further examined the effect of CD3+ and CD34+ cell doses on aGVHD using quartile cutoff points and found a minimum threshold for CD3+ (38 × 106/kg) and CD34+ (4 × 106/kg) cells above which the incidence of grade 2-4 aGVHD is significantly increased. This study shows for the first time a positive correlation between the number of CD3+ and CD34+ cells and aGVHD in children receiving sibling BMT, and indicates that using tailored and more intensive post transplant immunosuppression may permit to better control aGVHD. [ABSTRACT FROM AUTHOR]

To investigate an association between KI and WU polyomavirus (KIPyV and WUPyV) infections and CD4+ cell counts, we tested HIV-1-positive patients and blood donors. No association was found between cell counts and virus infections in HIV-1-positive patients. Frequency of KIPyV infection was similar for both groups. WUPyV was more frequent in HIV-1-positive patients. [ABSTRACT FROM AUTHOR]

Three different methods for determination of CD34+ cells in G-CSF-mobilized peripheral blood were compared. The methods were: the Milan/Mulhouse protocol, the ISHAGE guidelines for CD34+ cells enumeration and our own protocol. The procedure we have adopted is essentially a Milan/Mulhouse protocol-derived methodology combined with a multiparametric approach using the PAINT-A-GATE software analysis program. The samples were collected from 70 patients affected by acute leukemia, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, myeloma and breast cancer who were scheduled to receive autologous PBSC transplantation. PBSC collection was performed following mobilization with subcutaneous G-CSF at 5–10 μg/kg/day. A minimum target of 2 × 106/kg CD34+ cells was considered an acceptable harvest to ensure a safe transplant. On average, three aphereses per patient were performed and a total of 204 apheresis samples were analyzed. Regression analysis of the percentage and absolute number of CD34+ cells, as calculated with each method, achieved an excellent correlation in spite of methodological differences. In fact, both CD34+dim and CD34+CD45- events were included in our gating strategy. In the setting of a triple staining associating CD34, CD38 and CD45, we identified a variable fraction of CD34+CD38+CD45- cells which would be otherwise undetected due to its CD45 negativity. To this end, we used a new technology referred to as laser-scanning cytometry (LSC) which allowed the isolation and morphological identification of CD34+CD45- cells. By comparing CD34+CD45+ and CD34+CD45- cells, we found that they share a common morphology, thus confirming the hypothesis that the latter are to be considered for CD34+ cell calculation. The median number of... [ABSTRACT FROM AUTHOR]

BACKGROUND PBPC transplantation has become a widely accepted therapeutic option for patients with chemotherapy-sensitive malignancies. PBPCs facilitate even the transplantation of mismatched allogeneic cells, because of their better engraftment. PBPCs are harvested by leukapheresis after mobilization with G-CSF or chemotherapy and G-CSF. To improve the purity and yield of PBPC grafts, to ensure reproducibility of the procedure and to reduce platelet loss in the patient/donor, different fully automated PBPC collection systems were developed. We report here our experience with the new Amicus blood cell separator. METHODS From July 2000 to March 2001, 46 procedures were performed. Six donors underwent leukaphereses after G-CSF administration (10-12 microgr/Kg/day) beginning on day 4; 14 patients were harvested after chemotherapy and G-CSF or GM-CSF mobilization, when the peripheral CD34+ cell count was >20 cells/micrL. Peripheral venous access was preferred whenever possible, otherwise femoral or subclavian catheters were used. Complete cell counts and CD34+ cell evaluations were done both in patients and donors, before and after each procedure and in all the products of the apheresis. RESULTS A median of 8.959 L of blood (range 3.585-17.021 ) was processed with a duration of 315 minutes (range 215-400) at a blood flow rate of 40 ml/min (range 25-70). ACD was used at a ratio of 1:14. The products of apheresis had a median volume of 143 ml (range 70-306) and a Hct of 12.9% (range 1.6-21). Platelet contamination was low (722 × 10[sup 9]/L, range 55-1,620), according to a low collection efficiency (12%, range 2-34) and a low decrease of platelet level both in donors and patients (21 × 10[sup 9]/L, range 3-83); in contrast, CD34 + cell collection efficiency was high (59.5%, range 15-97). No adverse affects were observed. CONCLUSIONS Amicus blood cell separator has a high collection efficiency for PBPC collections and improves donor safety by reducing platelet loss. [ABSTRACT FROM AUTHOR]

Thalassemic diseases are characterized by a reduced (β + ) or absent (β 0 ) synthesis of the globin chains of hemoglobin (Hb) due to genetic mutations. β-thalassemia was more frequent in the Mediterranean area, but now it is diffused worldwide. Three possible genetic forms can be distinguished: β 0 /β 0 , the most severe (Cooley's disease); β 0 /β + of intermediate severity; β + /β + associated with β-thalassemia intermedia or minor. Recently, a clinical non-genetic classification has been proposed: transfusion-dependent thalassemia (TDT), requiring regular lifetime blood transfusions, and non-transfusion-dependent thalassemia (NTDT), requiring occasional transfusions to manage acute cases. In this report, we studied a patient whose blood count indicated a severe anemia but also showed thrombocytosis, leukocytosis, and an elevated number of nucleated red blood cells (NRBC). These altered blood parameters suggested initially a possible diagnosis of hemoglobinopathy or myeloproliferative syndrome. The molecular and genetic analyses demonstrated the presence of HbF (5.3%) and HbA2 (7.7%) and the presence of the homozygote mutation (IVS1.6T>C) in the β-globin gene. According to these data, a diagnosis of β-thalassemia intermedia form has been proposed. Nevertheless, the clinical condition, the presence of thrombocytosis, leukocytosis, an elevated number of NRBC, and the frequent blood transfusions lead to reclassification of the patient as TDT subject. Consequently, this result suggests that a unique genotype-phenotype correlation is not possible in the presence of β + mutations since other concomitant pathologies can exacerbate the disease., Competing Interests: The authors declare that they have no conflict of interest., (Copyright 2024, Castelgrande et al.)

A urine test permits the measure of several urinary markers. This is a non-invasive method for early monitoring of potential kidney damage. In COVID-19 patients, alterations of urinary markers were observed. This review aims to evaluate the utility of urinalysis in predicting the severity of COVID-19. A total of 68 articles obtained from PubMed studies reported that (i) the severity of disease was related to haematuria and proteinuria and that (ii) typical alterations of the urinary sediment were noticed in COVID-19-associated AKI patients. This review emphasizes that urinalysis and microscopic examination support clinicians in diagnosing and predicting COVID-19 severity.

Among the surrounding cells influencing tumor biology, platelets are recognized as novel players as they release microvesicles (MVs) that, once delivered to cancer cells, modulate signaling pathways related to cell growth and dissemination. We have previously shown that physiological delivery of platelet MVs enriched in miR-126 exerted anti-tumor effects in different breast cancer (BC) cell lines. Here, we seek further insight by identifying AKT2 kinase as a novel miR-126-3p direct target, as assessed by bioinformatic analysis and validated by luciferase assay. Both ectopic expression and platelet MV-mediated delivery of miR-126-3p downregulated AKT2 expression, thus suppressing proliferating and invading properties, in either triple negative (BT549 cells) or less aggressive Luminal A (MCF-7 cells) BC subtypes. Accordingly, as shown by bioinformatic analysis, both high miR-126 and low AKT2 levels were associated with favorable long-term prognosis in BC patients. Our results, together with the literature data, indicate that miR-126-3p exerts suppressor activity by specifically targeting components of the PIK3/AKT signaling cascade. Therefore, management of platelet-derived MV production and selective delivery of miR-126-3p to tumor cells may represent a useful tool in multimodal therapeutic approaches in BC patients.

A matched-pair analysis of transplant-related outcomes was carried out in 116 of 255 consecutive patients who received transplants from an HLA identical sibling (n = 58) or haploidentical related donor (n = 58). The 2 patient series were matched with 9 variables: period of transplant, patient and donor age, sex, diagnosis, disease phase, conditioning regimen, donor-recipient sex, and cytomegalovirus (CMV) status combinations. As graft-versus-host disease (GVHD) prophylaxis, all patients received the standard cyclosporine and methotrexate association with the addition of anti-thymocyte globulins, mycophenolate mofetil, and basiliximab in haploidentical, unmanipulated bone marrow recipients. Anti-infectious management, transfusion policy, and supportive care were identical for all patients. By comparing the 2 patient series, no statistically significant difference was observed for the cumulative incidence of advanced acute and extensive chronic GVHD, transplant-related mortality, and relapse. With a median follow-up of 3.5 years, the 5-year disease-free survival was 37% ± 6% and 36% ± 6% for HLA identical sibling and haploidentical recipients, respectively. The results of transplant from HLA identical siblings and haploidentical donors are comparable. Regardless of the HLA matching, other factors known to affect the transplant outcomes, such as donor-recipient age, sex, and CMV status combinations, might drive the search for the best donor., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Breast cancer is one of the most frequent and malignant types of cancer in women, with an increasing morbidity and mortality rate; in particular, treatment of triple negative breast cancer remains a challenge, since the efforts made with targeted therapies were ineffective. Among surrounding cells influencing the biology of cancer cells, platelets are recognizing as novel players. Activated platelets release microvesicles (MVs) that, once delivered to cancer cells, modulate signaling pathways related to cell growth and dissemination; among factors contained in platelet-derived MVs, microRNAs are highly involved in cancer development. The growing interest in ω3 and ω6 polyunsaturated fatty acids (PUFAs) as adjuvants in anti-cancer therapy prompted us to investigate the ability of arachidonic acid (AA) and docosahexaenoic acid (DHA) to modulate MV biological functions. AA induced differential enhancement of platelet-specific microRNAs (miR-223 and miR-126), an effect further enhanced by the presence of DHA. MVs can be delivered to and microRNAs internalized by breast cancer cells, although with different efficiency; analysis of kinetics of MV delivery, indeed, suggested that tumor cells fine-tune the uptake of specific microRNA. Finally, we demonstrated that physiological delivery of platelet miR-223 and miR-126 induced cellular effects in breast cancer cells, including cell cycle arrest, inhibition of migration and sensitivity to cisplatin. These results have been confirmed by exogenous expression of miR-223 and miR-126 through transient transfection experiments. Our preliminary data suggest that ω6/ω3-PUFA supplementation, by modulating microRNA delivery, enhances platelet anti-tumor activities, thus opening new avenues for add-on therapies in cancer patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The term "emerging elders" has surfaced in age-friendly community assessment tools to denote a subset of older adults; however, limited guidance is provided on its application to aging populations. The goal of this study was to develop a data-driven conceptualization of "emerging elders" as part of an age-friendly community assessment. Adults, aged 55 years and above, were asked about their subjective meaning of "emerging elder" within the context of a larger study of aging well in a large U.S. metropolitan city. Using inductive and deductive methods, the researchers analyzed qualitative data ( N = 38) collected from individual interviews with homebound older adults ( n = 15) and participants of three focus groups ( n = 23). Four themes suggest that emerging elderhood is related to chronological age, functional ability, transitions, and self-identity. Findings suggest that the term emerging elderhood may foster negative images of older adults consistent with Western cultural discourse, despite the positive connotations associated with "emerging elder" in indigenous and spiritual communities. Findings underscore the need to further refine age-friendly community assessments that take into account the social constructions ascribed to older adults and need for strategies to engage emerging elders in future research of age-friendly communities., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Using a social capital and social cohesion lens, we reposition the concept of civic engagement among older adults to examine pathways for building age-friendly communities. We analyzed data drawn from a Community-Based Participatory Research study in the Southern U.S. that explored lived experiences of older adults, age 55 and above, who participated in individual interviews (n = 15) and six focus group discussions (n = 45) to examine their perceptions of social identity, social connectedness, and civic engagement geared toward an age-friendly city. Findings indicated that several older adults had access to social networks and socially invested resources, thereby having opportunities for civic engagement and building age-friendly neighborhoods. However, social, cultural, linguistic, and structural barriers were more evident among certain diverse ethnic populations. Marginalized low-income minorities and immigrants, such as Hispanic participants, felt the lack of social cohesion among the larger society limited their ability to give back, thus decreasing their civic engagement activities. In contrast, Caucasian and African-American older adults were able to contribute to the political process through more civic participation activities. We provide implications for examining the role of social capital and social engagement to bolster civic engagement among older adults in building age-friendly communities.

In the attempt of purging the HIV-1 reservoir through the "shock-and-kill" strategy, it is important to select latency-reversing agents (LRAs) devoid of deleterious effects on the antiviral function of immune effector cells. Here, we investigated two LRAs with PKC agonist activity, prostratin (PRO) and bryostatin-1 (BRY), for their impact on the function of natural killer (NK) cells, the major effectors of innate immunity whose potential in HIV-1 eradication has emerged in recent clinical trials. Using NK cells of healthy donors, we found that exposure to either PRO or BRY potently activated NK cells, resulting in upmodulation of NKG2D and NKp44 activating receptors and matrix metalloprotease-mediated shedding of CD16 receptor. Despite PRO and BRY affected NK cell phenotype in the same manner, their impact on NK cell function was diverse and showed considerable donor-to-donor variation. Altogether, in most tested donors, the natural cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) of NK cells were either improved or maintained by PRO, while both activities were impaired by BRY. Moreover, we analyzed the effect of these drugs on the capacity of treated NK cells to kill autologous latently infected CD4 + T cells reactivated via the same treatment. First, we found that PRO but not BRY increased upmodulation of the ULBP2 ligand for NKG2D on reactivated p24 + cells. Importantly, we showed that clearance of reactivated p24 + cells by NK cells was enhanced when both targets and effectors were exposed to PRO but not to BRY. Overall, PRO had a superior potential compared with BRY as to the impact on key NK cell functions and on NK-cell-mediated clearance of the HIV-1 reservoir. Our results emphasize the importance of considering the effects on NK cells of candidate "shock-and-kill" interventions. With respect to combinative approaches, the impact on NK cells of each LRA should be re-evaluated upon combination with a second LRA, which may have analogous or opposite effects, or with immunotherapy targeting NK cells. In addition, avoiding co-administration of LRAs that negatively impact ADCC activity by NK cells might be essential for successful application of antibodies or vaccination to "shock-and-kill" strategies.

Objective: This study focused on understanding positive aspects of cancer among a large, national sample of survivors, 2, 5, and 10 years' postcancer diagnosis, who responded to the American Cancer Society Study of Cancer Survivors - II (SCS-II) survey "Please tell us about any positive aspects of having cancer.", Methods: A sequential mixed methods approach examined (1) thematic categories of positive aspects from cancer survivors (n = 5149) and (2) variation in themes by sociodemographics, cancer type, stage of disease, and length of survivorship., Results: Themes comprised 21 positive aspects within Thornton's typology of benefits that cancer survivors attribute to their illness: life perspectives, self, and relationships. New themes pertaining to gratitude and medical support during diagnosis and treatment, health-related changes, follow-up/surveillance, and helping others emerged that are not otherwise included in widely used existing benefit finding cancer scales. Gratitude and appreciation for life were the most frequently endorsed themes. Sociodemographics and stage of disease were associated with positive aspect themes. Themes were not associated with survivor cohorts., Conclusions: No differences in perceived positive aspects across survivor cohorts suggest that positive aspects of cancer may exist long after diagnosis for many survivors. However, variation across sociodemographics and clinical variables suggests cancer survivors differentially experience positive aspects from their cancer diagnosis., Implications for Cancer Survivors: This analysis provides new information about cancer survivors' perceptions of positive aspects from their cancer and factors associated with benefit finding and personal growth. This information can be useful in further refining quality-of-life measures and interventions for cancer survivors., (Copyright © 2017 John Wiley & Sons, Ltd.)