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Phase 2 study of natalizumab plus standard corticosteroid treatment for high-risk acute graft-versus-host disease.

Graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract is the main cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation. Ann Arbor (AA) scores derived from serum biomarkers at onset of GVHD quantify GI crypt damage; AA2/3 scores correlate with resistance to treatment and higher NRM. We conducted a multicenter, phase 2 study using natalizumab, a humanized monoclonal antibody that blocks T-cell trafficking to the GI tract through the α4 subunit of α4β7 integrin, combined with corticosteroids as primary treatment for patients with new onset AA2/3 GV

TIGIT/PVR axis regulates anti-tumor immunity in hematologic malignancies.

Hematologic malignancy stands as a grave form of cancer characterized by its arduous treatment and heightened likelihood of recurrence. Over the recent years, immunotherapy has progressively evolved into a pivotal approach for addressing hematologic malignancies. As a novel inhibitory receptor of NK and T cells, TIGIT is similar to PD-1, and blocking TIGIT can play a huge anti-tumor effect. At present, target TIGIT is still in clinical trials. Within this context, the TIGIT/PVR axis, serving as a pivotal element within the immunomodulatory framework, assumes a critical role in tumor immunity o

Upheaval in cancer care during the COVID-19 outbreak.

On Monday, 23 March 2020, Nigeria recorded its first mortality from the novel global COVID-19 outbreak. Before this, the country reported 36 confirmed cases (at the time of writing) and has discharged home two cases after weeks of care at a government-approved isolation centre in Lagos State. This first mortality was that of a 67-year-old man with a history of multiple myeloma, a type of blood cancer. He was undergoing chemotherapy and had just returned to Nigeria following medical treatment in the United Kingdom. The novel COVID-19 pandemic has grounded several global activities including the

Case Report: Application of ex-vivo drug sensitivity testing to identify personalized treatment options for an adolescent with diffuse midline glioma.

Diffuse midline glioma (DMG) is a pediatric brain cancer that has a dismal prognosis with limited treatment options. We present the treatment course and outcome of an adolescent male diagnosed with a thalamic DMG carrying a histone H3.3 K27M (H3K27M) alteration. Tumor biopsies were taken at diagnosis for histological analysis, molecular profiling, and ex vivo drug sensitivity testing (DST). Seven months after diagnosis, the patient had recurrent/progressive disease after radiotherapy and an ineffective molecular-guided therapy based on tumor molecular profiling. The patient then started a nove

Trametinib: A Targeted Therapy in Metastatic Melanoma.

Trametinib is a MEK inhibitor approved both as a single agent and in combination with dabrafenib for the treatment of BRAF V600E or V600K mutated melanoma. It is a once-daily oral medication that was approved based on progression-free survival and overall survival advantage compared to chemotherapy. Most common side effects include rash, diarrhea, peripheral edema, and fatigue. When used in combination with dabrafenib, pyrexia and nausea are also common. Most side effects can be managed effectively with dose interruptions, supportive care, and/or dose reductions. Ongoing trials are investigati

A Borate-Based Bioactive Glass Advances Wound Healing in Non-Healing Wagner Grade 1 Diabetic Foot Ulcers: A Randomised Controlled Clinical Trial.

A novel advanced synthetic bioactive glass matrix was studied in patients with non-healing diabetic foot ulcers (DFUs). Bioactive glasses can be constructed to be biocompatible, with water-soluble materials in multiple geometries including fibre scaffolds that mimic the 3D architecture of a fibrin clot. In this trial, chronic, Wagner Grade 1 DFUs were randomised to receive borate-based bioactive glass Fibre Matrix (BBGFM) plus standard of care (SOC) therapy for 12 weeks or SOC alone. The primary study endpoint was the proportion of subjects that obtained complete wound closure at 12 weeks. Sec

Research in haematological cancers: What do patients in the Netherlands prioritise?

IntroductionThe experiential knowledge of patients can provide research communities with complementary perspectives on disease. The aim of this study was to identify and prioritise everyday problems and research needs of haematological cancer patients and people who have undergone a stem cell transplantation.MethodsA mixed-method participatory research approach (the Dialogue Model) was applied, including interviews (n = 19), four focus group discussions (n = 27), a questionnaire (n = 146) and a stakeholder dialogue meeting (n = 30) with patients in the Netherlands.ResultsPatients' physical dis

Improvements in Air Quality and Health Outcomes Among California Medicaid Enrollees Due to Goods Movement Actions.

INTRODUCTION: In 2006, the California Air Resources Board (CARB) and local air quality management districts implemented an Emission Reduction Plan for Ports and Goods Movement program (referred to hereinafter as GM policy actions) (CARB 2006). The GM policy actions comprise approximately 200 actions with an estimated investment value of $6 to $10 billion. These actions targeted the major sources and polluters related to goods movements, such as highways; ports and railyard trucks; ship fuel and shore power; cargo equipment; and locomotives. These actions aimed to reduce total statewide domesti

Occupational exposure to ionizing radiation and risk of lymphoma subtypes: results of the Epilymph European case-control study.

BackgroundEvidence linking risk of lymphoma and B-cell lymphoma subtypes to ionizing radiation is inconclusive, particularly at low exposure levels.MethodsWe investigated risk of lymphoma (all subtypes), B-cell lymphomas, and its major subtypes, associated with low-level occupational exposure to ionizing radiation, in 2346 lymphoma cases and 2463 controls, who participated in the multicenter EpiLymph case-control study. We developed a job-exposure matrix to estimate exposure to ionizing radiation, distinguishing between internal and external radiation, and we applied it to the lifetime occupat

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… Baggage control personnel in ship boarding was considered as unexposed, as the use of x -rays for screening baggage and personal belongings before allowing boarding onto ships was introduced when recruitment of study subjects was approximately completed. …

Balancing Quality, Cost, and Access During Delivery of Newer Cellular and Immunotherapy Treatments.

Purpose of reviewThe chimeric antigen receptor (CAR) T-cell therapy is currently changing the landscape of hematologic malignancies with multiple FDA-approved cell therapy products in the USA. The current administration process of the CAR T-cell therapy is complicated, labor-intensive, and expensive.Recent findingsThe chimeric antigen receptor (CAR) T-cell therapy is currently changing the landscape of hematologic malignancies with multiple FDA-approved cell therapy products in the USA. The current administration process of the CAR T-cell therapy is complicated, labor-intensive, and expensive.

Incorporating patients' input in the development and validation of patient-reported outcome measures in oncology: a comprehensive scoping review.

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Vitamin D Deficiency-Associated Neuropathic Pain Examined in a Chronic Pain Management Program.

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First-in-human Study of AZD5153, A Small-molecule Inhibitor of Bromodomain Protein 4, in Patients with Relapsed/Refractory Malignant Solid Tumors and Lymphoma.

AZD5153, a reversible, bivalent inhibitor of the bromodomain and extraterminal family protein BRD4, has preclinical activity in multiple tumors. This first-in-human, phase I study investigated AZD5153 alone or with olaparib in patients with relapsed/refractory solid tumors or lymphoma. Adults with relapsed tumors intolerant of, or refractory to, prior therapies received escalating doses of oral AZD5153 once daily or twice daily continuously (21-day cycles), or AZD5153 once daily/twice daily continuously or intermittently plus olaparib 300 mg twice daily, until disease progression or unacceptab

Acute promyelocytic leukaemia in a Nigerian patient-a case report depicting challenges in the management of haematological malignancies in Nigeria.

IntroductionHaematological malignancies (HMs) account for approximately 10% of all malignancies in sub-Saharan Africa (SSA), and their incidence is rapidly increasing. Successful management of these malignancies depends on early presentation, diagnosis and prompt initiation of treatment. However, in SSA and many low and middle-income countries, several barriers hinder the effective management of these malignancies. This case report of a patient with acute promyelocytic anaemia highlights the challenges in managing HM.Case summaryA 31-year-old woman presented to a primary health care centre wit

Prevention of CMV/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation: results from the randomized phase I/IIa MULTIVIR-01 study.

INTRODUCTION: Allogeneic stem cell transplantation is used to cure hematologic malignancies or deficiencies of the hematopoietic system. It is associated with severe immunodeficiency of the host early after transplant and therefore early reactivation of latent herpesviruses such as CMV and EBV within the first 100 days are frequent. Small studies and case series indicated that application of herpes virus specific T cells can control and prevent disease in this patient population. METHODS: We report the results of a randomized controlled multi centre phase I/IIa study (MULTIVIR-01) using a new

Therapeutic Apheresis Using a β2-Microglobulin Removal Column Reduces Circulating Tumor Cell Count.

An elevated serum β2-microglobulin (β2M) level is indicative of impaired glomerular filtration and prerenal diseases, such as malignant tumors, autoimmune disorders, and liver diseases. An elevated serum β2M level has been shown to promote metastasis via the induction of epithelial-mesenchymal transition (EMT) in cancer cells. However, the therapeutic potential of targeting β2M remains unclear. Here, we aimed to investigate the efficacy of Filtor, a small polymethyl methacrylate fiber-based β2M removal column, in reducing the β2M level and suppressing cancer cell-induced EMT and metastasis. We

PROTECT Trial: A cluster-randomized study with hydroxychloroquine versus observational support for prevention or early-phase treatment of Coronavirus disease (COVID-19): A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: Hydroxychloroquine has shown to have antiviral activity in vitro against coronaviruses, specifically SARS-CoV-2. It is believed to block virus infection by increasing endosomal pH required for virus cell fusion and glycosylation of viral surface proteins. In addition to its antiviral activity, hydroxychloroquine has an immune-modulating activity that may synergistically enhance its antiviral effect in vivo, making it a potentially promising drug for the prevention and the cure of SARS-CoV-19. However, randomized controlled trials are needed to assess whether it can be used safely t

Characteristics and advances in signaling pathways, cellular communication, cell junctions, and oxidative stress in lymphedema.

Lymphedema is a chronic inflammatory disease without an effective treatment method, and it results in a high disease burden and psychological distress in patients. Although there have been significant advances in targeted therapies, there are still no effective options to treat this refractory disease. In recent years, new advances and breakthroughs have been made in signaling pathways, including RAS/MAPK, PI3K/AKT, VEGF-C/VEGFR-3, HGF/MET, and TGF-β1, which are important for understanding the pathogenesis and disease progression of lymphedema. Mutations in genes encoding cell junctions affect

Распределение основных HLA-A, -B, -DR и -DQ Loci потенциально ассоциируется с множественным склерозом в здоровом населении Южного Марокко.

Справочная информация: Многие факторы способствуют развитию и развитию молекулы Множественного склероза (MS), включая молекулы лейкоцита (HLA). Некоторые из них считаются предрасположенными, например DRB1*15, DRB1*13, DRB1*03, DQB1*04, DQB1*06, DQB1*02, в то время как HLA A2, HLA B44, DRB1*11 и DRB1*12 считаются скорее защитными. Данные о таких ассоциациях марокканского населения остаются неизвестными. Цель этого исследования состояла в том, чтобы определить частотность использования классов I (A и B) и II (DR и DQ) HLA, связанных с множественным склерозом (MS) в здоровом населении на юге Маро

Изучение клинической полезности нееврофильтрованных световых цепочек для управления множественным склерозом.

Множественный склероз (MS) — хроническое нервно-воспалительное и нейродегенеративное заболевание, которое воздействует почти на здоровье человека. 1 million взрослых в Соединенных Штатах. В связи с непредсказуемостью курса лечения заболеваний, разнообразием фенотипов и целым рядом имеющихся в настоящее время методов лечения, позволяющих видоизменить заболевания, требуется индивидуализированный подход к управлению MS. Существует неудовлетворенная потребность в выявлении, подтверждении и включении прогнозных, мониторинговых и прогнозных биомаркеров в обычную клиническую практику для MS. Усиливаю