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MSD R&D Innovation Centre[Affiliation] Publications | LitMetric

7,656 results match your criteria: "MSD R&D Innovation Centre[Affiliation]"

Background: Iron deficiency anemia in the perioperative setting is treated predominantly with intravenous iron formulation, of which ferric carboxymaltose may induce hypophosphatemia by modulating fibroblast growth factor 23.

Methods: In this single-center, prospective, randomized, double-blind trial, we consented 92 adult patients scheduled for elective major abdominal or thoracic surgery. These patients either had isolated iron deficiency (plasma ferritin <100 ng/mL or transferrin saturation < 20 %) or iron deficiency anemia (hemoglobin (Hb) 100-130 g/L with plasma ferritin <100 ng/mL or transferrin saturation < 20 %).

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Background: Rearrangement in anaplastic lymphoma kinase () occurs in 4-7% of non-small cell lung cancer (NSCLC) cases. Despite improved survival with tyrosine kinase inhibitors (TKIs), treatment resistance remains challenging. This retrospective study analyzed advanced ALK-positive NSCLC patients, focusing on clinical aspects, treatments, resistance, and outcomes.

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Article Synopsis
  • The study investigates the limitations of immunotherapies in treating high-grade serous ovarian cancer (HGSOC) and explores the potential of combining immunotherapy with PARP inhibitors, emphasizing the roles of BRCAness and the tumor microenvironment in treatment response.
  • Researchers performed detailed immunogenomic analyses and machine learning to identify a 24-gene signature predicting BRCAness, revealing high immune cell infiltration and an association with immunosuppressive cells in samples receiving combination therapies.
  • Findings indicate that PARP inhibitors can activate immune-related pathways similarly to genetic BRCAness, and the team has developed a web app for analyzing ovarian cancer samples and providing a vulnerability score for patient stratification.
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Background: Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease. Since it can lead to variable organ involvement, including life-threatening complications, and due to newly available therapeutic approaches, the German Society for Rheumatology and Clinical Immunology (Deutsche Gesellschaft für Rheumatologie und klinische Immunologie; DGRh) issued a newly developed S2e guideline in December 2022.

Objective: This study aims to investigate the influence of the new guideline on the diagnosis, management, and outcomes of AOSD.

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Background: Despite advances in radiation techniques, radiation cystitis (RC) remains a significant cause of morbidity from pelvic radiotherapy, which may affect patients' quality of life (QoL). The pathophysiology of RC is not well understood, which limits the development of effective treatments.

Objective: The Radiotoxicity Bladder Biomarkers study aims to investigate the correlation between blood and urinary biomarkers and the intensity of acute RC symptoms and QoL in patients undergoing localized prostate cancer radiotherapy.

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Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumour progression commonly occurs. Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity.

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Background: Intrauterine transfusions (IUTs) are a life-saving treatment for fetal anemia. However, with each transfusion, iron bypasses uptake regulation through the placenta and accumulates in fetal organs. Unlike other imaging modalities, fetal magnetic resonance imaging (MRI) is capable of non-invasively assessing fetal liver disease and/or organ iron overload.

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In recent years, great progress has been made in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) treatment for hematological malignant diseases because of the advent of novel conditioning regimens, optimized graft manipulation, improved graft-versus-host disease (GVHD) prophylaxis, and advances in supportive care. Recent studies have shown very favorable outcomes in severe aplastic anemia (SAA) patients, with comparable outcomes to those of patients receiving immune suppressive therapy (IST) and allogeneic HSCT from a matched sibling donor (MSD) or matched unrelated donor (MUD). However, most of the previous studies relied on single-center data analyses, and the conditioning regimen, GVHD prophylaxis and supportive care used were relatively singular.

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Background: Post-COVID-19 condition (PCC) affects millions of people, and is an essential component of the long-term impact of COVID-19 during the post-pandemic era. Yet, consensus on clinical case definition and core components of PCC remains lacking, affecting our ability to inform research and evidence-based management. Our study aims 1) to identify the most specific symptoms for PCC, and identify clinical subtypes; 2) to evaluate both virus- and host-related determinants of PCC, and 3) assess the impact of PCC on physical and mental health.

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Microsatellite instability-high (MSI-H) is a critical biomarker for immunotherapy, yet primary resistance remains a significant challenge. Current MSI-H detection methods evaluate the proportion of MSI-H loci, termed molecular MSI-H score, which can be affected by intratumoral heterogeneity (ITH). To address this limitation, we propose evaluating MSI-H at the cellular level to improve the prediction of immunotherapy outcomes.

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Motivation: The availability of longitudinal omics data is increasing in metabolomics research. Viewing metabolomics data over time provides detailed insight into biological processes and fosters understanding of how systems react over time. However, the analysis of longitudinal metabolomics data poses various challenges, both in terms of statistical evaluation and visualization.

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Article Synopsis
  • * A study involving nearly 2,000 non-resectable HCC patients showed that LMWA had comparable safety and overall survival rates to PRFA and significantly better survival rates than TACE after 1, 3, and 5 years.
  • * The results suggest that LMWA is a viable treatment option for early HCC, outperforming TACE while demonstrating similar efficacy to PRFA, which supports its potential inclusion in standardized treatment
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Background: Pain is the leading cause of disability and reduced quality of life worldwide. Despite the increasing burden for patients and healthcare systems, pain research remains underfunded and under focused. Having stakeholders identify and prioritize areas that need urgent attention in the field will help focus funding topics, reduce 'research waste', improve the effectiveness of pain research and therapy and promote the uptake of research evidence.

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Objectives: Anti-PD-(L)1 agents changed the landscape of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treatment. Previous studies showed improved response rates to salvage chemotherapy (SCT) after progression to anti-PD-(L)1 agents. This study aims to evaluate the outcomes of SCT and to identify predictors of response and survival in patients with R/M HNSCC.

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Partitioned polygenic risk scores identify distinct types of metabolic dysfunction-associated steatotic liver disease.

Nat Med

December 2024

Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by an excess of lipids, mainly triglycerides, in the liver and components of the metabolic syndrome, which can lead to cirrhosis and liver cancer. While there is solid epidemiological evidence that MASLD clusters with cardiometabolic disease, several leading genetic risk factors for MASLD do not increase the risk of cardiovascular disease, suggesting no causal relationship between MASLD and cardiometabolic derangement. In this work, we leveraged measurements of visceral adiposity identifying 27 previously unknown genetic loci associated with MASLD (n = 36,394), six replicated in four independent cohorts (n = 3,903).

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Article Synopsis
  • People with resistant hypertension (RH) face a greater risk of serious heart-related issues, prompting the British and Irish Hypertension Society to recommend specialist guidance for better blood pressure control.
  • The position statement offers a practical framework for diagnosing and managing adults with RH, while also addressing the current evidence gaps in the field.
  • The overall goal is to enhance the quality and consistency of care for individuals with RH throughout the UK and Ireland.
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Gut microbiome and metabolic dysfunction-associated steatotic liver disease: Pathogenic role and potential for therapeutics.

Best Pract Res Clin Gastroenterol

September 2024

Department of Gastroenterology, "Lozano Blesa" Clinical Hospital, 50009, Zaragoza, Spain; Aragón Health Research Institute (IIS Aragón), 50009, Zaragoza, Spain; School of Medicine, University of Zaragoza, 50009, Zaragoza, Spain.

Gut microbiota plays key functions in the human body, and its alteration is associated with several human disorders. Moreover, its manipulation is being investigated as a potential therapeutic strategy. In this narrative review we will dissect the involvement of the gut microbiota and of the gut-liver axis on metabolic dysfunction-associated steatotic liver disease (MASLD).

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Ph- ALL: immunotherapy in upfront treatment.

Hematology Am Soc Hematol Educ Program

December 2024

Department of Medicine A, Hematology and Oncology, University Hospital Münster, Münster, Germany.

Antibody-based and cell-based novel immunotherapies, such as bispecific T-cell engagers (BiTE), antibody-drug conjugates, or chimeric antigen receptor (CAR) T cells are currently standard treatment options for patients with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). To date, CD20-targeting monoclonal antibodies and the CD19-targeting BiTE's blinatumomab have been established elements of frontline therapy, either in patients with CD20+ ALL or in patients with measurable disease (MRD) following conventional chemotherapy. Recently, blinatumomab has also demonstrated a survival benefit in patients with MRD-negative ALL.

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Response.

Gastrointest Endosc

December 2024

Servicio de Medicina Digestiva, Hospital General Universitario Dr. Balmis, Instituto de Investigación Biomédica ISABIAL, Universidad Miguel Hernández, Alicante, Spain.

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Background: Cancer immunotherapy has revolutionized melanoma treatment, but the high number of non-responders still emphasizes the need for improvement of therapy. One potential avenue for enhancing anti-tumor treatment is through the modulation of coagulation and platelet activity. Both have been found to play an important role in the tumor microenvironment, tumor growth and metastasis.

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Purpose: Anidulafungin is recommended as a first-line treatment for invasive Candida infections in critically ill patients. Pharmacokinetic (PK) variability is large in critically ill patients, potentially compromising pharmacokinetic-pharmacodynamic (PKPD) target attainment under standard dosing. We aimed to assess anidulafungin exposure, PKPD target attainment, and population (pop)PK in critically ill patients.

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Radiotherapy showed synergy with immunotherapy, yet the comparative effectiveness of combining immunotherapy (iRT) or chemotherapy (CRT) after platinum therapy failure in advanced non-small cell lung cancer (NSCLC) remains unexplored. We analyzed 163 patients (iRT:  = 120 vs. CRT:  = 43) eligible for combination radiotherapy.

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Triple-negative breast cancer (TNBC) is challenging to treat because of its lack of specific molecular targets. The IMMUNOPEG study aimed to evaluate a novel structured method for interpreting TNBC immunohistochemistry specimens processed with VENTANA PD-L1 (SP142) assay. The study involved 10 pathologists who evaluated 50 different immunohistochemistry specimens of TNBC with programmed death ligand 1 (PD-L1) expression considered challenging and that were previously evaluated by the scientific committee, using the NAVIFY Digital Pathology platform.

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Article Synopsis
  • Pathologist assessment of tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer shows variability, but AI could standardize and enhance TIL scoring for better prognostic outcomes.
  • Ten AI models were tested for their analytical and prognostic validity using tissue samples from TNBC patients in both retrospective and prospective cohorts, revealing notable differences in performance across models.
  • Most AI models demonstrated significant prognostic validity related to anti-tumor immunity, suggesting that leveraging AI could improve clinical understanding and outcomes in TNBC patients.
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