Advantages of enteral nutrition over parenteral nutrition

It is a strong and commonly held belief among nutrition clinicians that enteral nutrition is preferable to parenteral nutrition. We provide a narrative review of more recent studies and technical reviews comparing enteral nutrition with parenteral nutrition. Despite significant weaknesses in the existing data, current literature continues to support the use of enteral nutrition in patients requiring nutrition support, over parenteral nutrition

Data-Driven Approaches to NBA Team Evaluation and Building

Gemstone Team PROCESSIn the National Basketball Association (NBA), it has historically been difficult to build and sustain a team that can consistently compete for championships. Given this challenge, we have developed a series of analyses to support NBA teams in making data-driven decisions. Relying on a variety of datasets, we examined several facets related to the construction of NBA rosters and their performance. In our analysis of on-court performance, we have used clustering algorithms to classify teams in terms of play style, and determined which play styles tend to lead to success. In our analysis of roster construction and transactions, we have investigated the relative value of draft picks and the impact of trades involving draft picks, as well as the effect of roster continuity (i.e. maintaining the same players across seasons) on team success. Additionally, we have developed a model for predicting player contract values and performance versus contract value, which will help teams in identifying the most cost-effective players to acquire. Ultimately, this assembly of analyses, in conjunction, can be used to inform any NBA team’s decisions in its pursuit of success

Sustained response off-treatment in eltrombopag-treated adult patients with ITP who are refractory or relapsed after first-line steroids: Primary, final, and ad-hoc analyses of the Phase II TAPER trial

Immune thrombocytopenia; Relapsed; SteroidsTrombocitopenia inmunitaria; Recaídas; EsteroidesTrombocitopènia immune; Recaiguda; EsteroidesImmune thrombocytopenia (ITP) is characterized by reduced platelet count due to increased destruction and is categorized according to the time following diagnosis (newly diagnosed, persistent, chronic). First-line corticosteroid therapy is associated with transient response, high relapse rates, and considerable toxicity. TAPER (NCT03524612) is a Phase II, prospective, single-arm trial investigating whether eltrombopag can induce a sustained response off-treatment (SRoT) in adult patients with ITP after first-line corticosteroid failure. This study defines SRoT as an off-treatment period wherein platelet count remains above 30 × 109/L in the absence of bleeding or rescue therapy. The primary endpoint was the proportion of patients who achieved SRoT until Month 12, which was 30.5% (n = 32/105; p 15%) following eltrombopag tapering and discontinuation, and median SRoT duration was ~8 months until Month 12. Median platelet count increased within 1 month of treatment and remained elevated until Month 12. Quality of life improved within 3 months and was maintained. Headache (21%) was the most common adverse event. None of the 4 deaths reported were considered treatment-related. In summary, ~one-third of patients achieved SRoT until Month 12 following eltrombopag tapering and discontinuation. An ad-hoc early-use analysis, stratified by ITP duration at baseline, assessed initial hematologic responses and safety. Results suggest that eltrombopag has similar efficacy in newly diagnosed and later stages of ITP. In follow-up until Month 24, a median SRoT duration of ~22 months was observed (n = 20). The safety profile was comparable across analyses and ITP duration groups and aligned with its well-established safety profile.Novartis Pharmaceuticals Corporation

Pevonedistat plus azacitidine vs azacitidine alone in higher-risk MDS/chronic myelomonocytic leukemia or low-blast-percentage AML

Pevonedistat; Chronic myelomonocytic leukemiaPevonedistat; Leucemia mielomonocítica crónicaPevonedistat; Leucèmia mielomonocítica crònicaPANTHER is a global, randomized phase 3 trial of pevonedistat+azacitidine (n = 227) vs azacitidine monotherapy (n = 227) in patients with newly diagnosed higher-risk myelodysplastic syndromes (MDS; n = 324), higher-risk chronic myelomonocytic leukemia (n = 27), or acute myeloid leukemia (AML) with 20% to 30% blasts (n = 103). The primary end point was event-free survival (EFS). In the intent-to-treat population, the median EFS was 17.7 months with pevonedistat+azacitidine vs 15.7 months with azacitidine (hazard ratio [HR], 0.968; 95% confidence interval [CI], 0.757-1.238; P = .557) and in the higher-risk MDS cohort, median EFS was 19.2 vs 15.6 months (HR, 0.887; 95% CI, 0.659-1.193; P = .431). Median overall survival (OS) in the higher-risk MDS cohort was 21.6 vs 17.5 months (HR, 0.785; P = .092), and in patients with AML with 20% to 30% blasts was 14.5 vs 14.7 months (HR, 1.107; P = .664). In a post hoc analysis, median OS in the higher-risk MDS cohort for patients receiving >3 cycles was 23.8 vs 20.6 months (P = .021) and for >6 cycles was 27.1 vs 22.5 months (P = .008). No new safety signals were identified, and the azacitidine dose intensity was maintained. Common hematologic grade ≥3 treatment emergent adverse events were anemia (33% vs 34%), neutropenia (31% vs 33%), and thrombocytopenia (30% vs 30%). These results underscore the importance of large, randomized controlled trials in these heterogeneous myeloid diseases and the value of continuing therapy for >3 cycles. The trial was registered on clinicaltrials.gov as #NCT03268954.This study was sponsored by Takeda Development Centers Inc (TDCA; Lexington, MA)

Multimedia Smart Process (MSP)

Traditional development processes do not include dynamic and creative aspects that exist in multimedia development environments. In these domains, creativity, design and animation are non-functional requirements that have great relevance in the final product and are often not considered in the implementation of traditional software. In this article, we make a comparison of the main traditional development processes and their suitability to the domains of multimedia software, proposing as an alternative Multimedia Smart Process (MSP)

Evaluation of the outcomes of newly diagnosed patients with high-risk myelodysplastic syndrome according to the initial therapeutical strategies chosen in usual clinical practice

Clinical practice; Myelodysplastic syndrome; TreatmentPràctica clínica; Síndrome mielodisplàstica; TractamentPráctica clínica; Síndrome mielodisplásico; TratamientoMyelodysplastic syndromes (MDS) are a heterogeneous group of diseases without a care standard and show variability in treatment outcomes. This Spanish, observational, prospective study ERASME (CEL-SMD-2012-01) assessed the evolution of newly diagnosed and treatment-naïve high-risk MDS patients (according to IPPS-R). 204 patients were included: median age 73.0 years, 54.4% males, 69.6% 0-1 ECOG, and 94.6% with comorbidities. Active treatment was the most common strategy (52.0%) vs. stem cell transplantation (25.5%) and supportive care/watchful-waiting (22.5%). Overall (median) event-free survival was 7.9 months (9.1, 8.3, and 5.3); progression-free survival: 10.1 months (12.9, 12.8, and 4.3); and overall survival: 13.8 months (15.4, 14.9; 8.4), respectively, with significant differences among groups. Adverse events (AEs) of ≥3 grade were reported in 72.6% of patients; serious AEs reported in 60.6%. 33.1% of patients died due to AEs. Three patients developed second primary malignant neoplasms (median: 8.2 months). Our study showed better outcomes in patients receiving active therapy early after diagnosis

Lymphoid and myeloid immune cell reconstitution after nicotinamide-expanded cord blood transplantation

Immunologia; Recerca mèdicaInmunología; Investigación médicaImmunology; Medical researchOmidubicel (nicotinamide-expanded cord blood) is a potential alternative source for allogeneic hematopoietic cell transplantation (HCT) when an HLA-identical donor is lacking. A phase I/II trial with standalone omidubicel HCT showed rapid and robust neutrophil and platelet engraftment. In this study, we evaluated the immune reconstitution (IR) of patients receiving omidubicel grafts during the first 6 months post-transplant, as IR is critical for favorable outcomes of the procedure. Data was collected from the omidubicel phase I-II international, multicenter trial. The primary endpoint was the probability of achieving adequate CD4+ T-cell IR (CD4IR: > 50 × 106/L within 100 days). Secondary endpoints were the recovery of T-cells, natural killer (NK)-cells, B-cells, dendritic cells (DC), and monocytes as determined with multicolor flow cytometry. LOESS-regression curves and cumulative incidence plots were used for data description. Thirty-six omidubicel recipients (median 44; 13–63 years) were included, and IR data was available from 28 recipients. Of these patients, 90% achieved adequate CD4IR. Overall, IR was complete and consisted of T-cell, monocyte, DC, and notably fast NK- and B-cell reconstitution, compared to conventional grafts. Our data show that transplantation of adolescent and adult patients with omidubicel results in full and broad IR, which is comparable with IR after HCT with conventional graft sources

Single-cell Multiomics Analysis of Myelodysplastic Syndromes and Clinical Response to Hypomethylating Therapy

Multiomics; Myelodysplastic syndromes; Hypomethylating therapyMultiómica; Síndromes mielodisplásicos; Terapia hipometilanteMultiòmica; Síndromes mielodisplàstics; Teràpia hipometilantAlterations in epigenetic marks, such as DNA methylation, represent a hallmark of cancer that has been successfully exploited for therapy in myeloid malignancies. Hypomethylating agents (HMA), such as azacitidine, have become standard-of-care therapy to treat myelodysplastic syndromes (MDS), myeloid neoplasms that can evolve into acute myeloid leukemia. However, our capacity to identify who will respond to HMAs, and the duration of response, remains limited. To shed light on this question, we have leveraged the unprecedented analytic power of single-cell technologies to simultaneously map the genome and immunoproteome of MDS samples throughout clinical evolution. We were able to chart the architecture and evolution of molecular clones in precious paired bone marrow MDS samples at diagnosis and posttreatment to show that a combined imbalance of specific cell lineages with diverse mutational profiles is associated with the clinical response of patients with MDS to hypomethylating therapy. Significance: MDS are myeloid clonal hemopathies with a low 5-year survival rate, and approximately half of the cases do not respond to standard HMA therapy. Our innovative single-cell multiomics approach offers valuable biological insights and potential biomarkers associated with the demethylating agent efficacy. It also identifies vulnerabilities that can be targeted using personalized combinations of small drugs and antibodies.We thank CERCA Programme/Generalitat de Catalunya for institutional support. The Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia has provided funding to M. Esteller (2017 SGR1080 and 2021 SGR01494) and F. Solé (2017 SGR288 and 2021 SGR00560). M. Esteller has also received funding from the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033/EDRF “A way to make Europe” (RTI2018-094049-B-I00 and PID2021-125282OB-I00), Cellex Foundation (CEL007) and “la Caixa” Foundation (LCF/PR/HR22/00732). F. Solé has also received funding from the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness (PI/17/00575 and PI 20/00531) and AECC/ISCIII TRANSCAN (AC18/000002). I. Campillo-Marcos is funded by a Juan de la Cierva-Formación fellowship from the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033 NextGenerationEU/PRTR (FJC2020-044658-I). G. Ferrer is the recipient of a Marie Skłodowska-Curie Action individual fellowship (H2020-MSCA-IF-2019-896403). We also thank Gema Fuerte (Mission Bio) for her support during sample processing and analysis