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A SITC vision: adapting clinical trials to accelerate drug development in cancer immunotherapy.

Clinical trials of cancer immunotherapy (IO) were historically based on a drug development paradigm built for chemotherapies. The remarkable clinical activity of programmed cell death protein 1/programmed death ligand 1 blockade, chimeric antigen receptor-T cells, and T cell engagers yielded new insights into how the mechanistic underpinnings of IO are reflected in the clinic. These insights and the sheer number of novel immunotherapies currently in the pipeline have made it clear that our strategies and tools for IO drug development must adapt. Recent innovations like engineered T cells and t

Что едят австра利йцы? Систематический обзор диетических паттернов и нежелательных здоровых последствий.

CONTEXT: Недостаточная диета является одним из основных факторов, влияющих на текущую нагрузку хронических заболеваний. В Австралии факторы питания вносят вклад в одну пятую часть нагрузки хронических заболеваний. Понимание диетических паттернов взрослых Австралии и суммирование их влияния на хронические состояния являются необходимыми для улучшения интервенций, направленных на поведение питания. OBJECTIVE: Настоящая систематическая проверка направлена на обобщение диетических паттернов взрослых Австралии, полученных с использованием методов постаппаративного и гибридного анализа, и их ассоци

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… Wu F, Wills K, Laslett LL, Oldenburg B, Jones G, Winzenberg T. Associations of dietary patterns with bone mass, muscle strength and balance in a cohort of Australian middle-aged women. Br J Nutr. 2017;118:598-606. 85. Zabetian-Targhi F, Srikanth VK, Smith KJ, et al. …

Цифровой дистанционный мониторинг людей с множественным склерозом.

ВВЕДЕНИЕ: Множественный склероз (MS) является хроническим нейродегенеративным заболеванием, которое затрагивает более 2,8 млн. человек во всем мире и приводит к значительным симптомам моторного и немоторного происхождения. Эффективный мониторинг заболеваний имеет решающее значение для улучшения результатов лечения пациентов, но часто затрудняется ограниченностью редких клинических оценок. Цифровые средства дистанционного мониторинга с использованием больших данных, и МА открывает новые возможности для отслеживания симптомов в режиме реального времени и выявления развития заболеваний. МЕТОДЫ: В

Создание Visualization of Digital Mobility Outlooks: Delphi-Type Process with Peoples.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Последние технологические достижения в области изношенных устройств открывают новые возможности для измерения мобильности в реальных условиях. " Mobilise-D " подтвердила результаты цифровой мобильности для получения новых результатов и конечных точек в клинических исследованиях 4 различные долгосрочные заболевания (болезнь Паркинсона, множественный склероз, хроническая обструктивная легочная болезнь и проксимальный бедренный перелом). Эти результаты также дают уникальную информацию, которая имеет важное значение для пациентов; однако имеется ограниченная литера

A probiotic approach identifies a Treg-centred immunoregulation via modulation of gut microbiota metabolites in people with multiple sclerosis and healthy individuals.

BACKGROUND: Modulation of the gut microbiota composition has been suggested as a potential disease modifying therapy in immune-mediated diseases such as multiple sclerosis (MS). However, a conclusive mechanism linking gut microbiota modulation to peripheral immune responses has remained elusive so far. METHODS: In this exploratory cohort study, people with MS (pwMS) and healthy controls (HC) supplemented a lactobacilli-rich probiotic for two or six weeks and were additionally investigated six weeks after the last intake. Immune cell phenotyping was performed in blood samples, complemented by

Re-estimation of the burden of serious fungal diseases in Uganda.

BACKGROUND: It is of utmost importance to monitor any change in the epidemiology of fungal diseases that may arise from a change in the number of the at-risk population or the availability of local data. OBJECTIVE: We sought to update the 2015 publication on the incidence and prevalence of serious fungal diseases in Uganda. METHODS: Using the Leading International Fungal Education methodology, we reviewed published data on fungal diseases and drivers of fungal diseases in Uganda. Regional or global data were used where there were no Ugandan data. RESULTS: With a population of ~45 million, w

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… New Engl J Med 1981 ; 305 : 1431 – 1438 . 6975437 10.1056/NEJM198112103052402 84 Wills NK Lawrence DS Botsile E , et al . The prevalence of laboratory-confirmed Pneumocystis jirovecii in HIV-infected adults in Africa: a systematic review and meta-analysis . …

Polycythemia Vera: Barriers to and Strategies for Optimal Management.

Polycythemia vera (PV) is a subtype of myeloproliferative neoplasms characterized by impaired quality of life and severe complications. Despite the increasingly in-depth knowledge of this condition, it necessitates a multifaceted management approach to mitigate symptoms and prevent thrombotic and hemorrhagic events, ensuring prolonged survival. The therapeutic landscape has been revolutionized in recent years, where venesection and hydroxycarbamide associated with antiplatelet therapy have a central role and are now accompanied by other drugs, such as interferon and Janus kinase inhibitors. On

'I think it affects every aspect of my life, really': Cancer survivors' experience of living with chronic pain after curative cancer treatment in England, UK.

AimTo explore cancer survivors' experiences of living with chronic pain after curative cancer treatment in England, UK.MethodsA qualitative study using telephone interviews with adult cancer survivors experiencing chronic pain after curative cancer treatment. Interview data was analysed using a reflexive thematic approach [1-3].FindingsNineteen participants: 14 female, 5 male, mean age 62.4 years, 1.5-48 years since cancer diagnosis, eight tumour groups represented. Six participants (31.6%) developed chronic pain more than ten years after completing cancer treatment (range 0-25 years). Five th

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

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… J Infect Dis ( 2002 ) 185 ( 8 ): 1025–34 . doi: 10.1086/339963 11930311 25 Weekes MP Wills MR Mynard K Carmichael AJ Sissons JG . …

Связь сексуальных отношений с гиперсексуальностью и проблемным использованием порнографии

Предыдущие исследования показали, что конкретные подходы, связанные с моральными убеждениями, могут играть важную роль в развитии и сохранении проблемных симптомов сексуального поведения. Однако, хотя другие виды отношения, такие, как сексуальное отношение, потенциально весьма актуальны, они пока еще не изучены в этой связи. Мы изучили, каким образом четыре аспекта сексуального поведения: дискредитация, контроль за рождаемостью, соединение и инструментальность, способствуют проблематичному использованию порнографии (PPU) и симптомам гиперсексуального расстройства (HD), контролируя религиозност

"Is this the GVHD?" A qualitative exploration of quality of life issues in individuals with graft-versus-host disease following allogeneic stem cell transplant and their experiences of a specialist multidisciplinary bone marrow transplant service.

BackgroundGraft-versus-host disease (GVHD) is a significant cause of morbidity and mortality following allogeneic stem cell transplantation. These patients face unique challenges due to the complexity of GVHD which can affect multiple organ systems, and the toxicity of treatments. Despite the known impact on quality of life (QOL), qualitative data within the bone marrow transplantation (BMT) literature is rare, and there has been no qualitative work exploring patient experience of specialist healthcare provision for GVHD in the United Kingdom.MethodsWe conducted a primary explorative qualitati

Mechanistic Quantitative Pharmacology Strategies for the Early Clinical Development of Bispecific Antibodies in Oncology.

Bispecific antibodies (bsAbs) have become an integral component of the therapeutic research strategy to treat cancer. In addition to clinically validated immune cell re-targeting, bsAbs are being designed for tumor targeting and as dual immune modulators. Explorative preclinical and emerging clinical data indicate potential for enhanced efficacy and reduced systemic toxicity. However, bsAbs are a complex modality with challenges to overcome in early clinical trials, including selection of relevant starting doses using a minimal anticipated biological effect level approach, and predicting effic

Forgoing life-sustaining treatment - a comparative analysis of regulations in Japan, Korea, Taiwan, and England.

BackgroundRegulations on forgoing life-sustaining treatment (LST) have developed in Asian countries including Japan, Korea and Taiwan. However, other countries are relatively unaware of these due to the language barrier. This article aims to describe and compare the relevant regulatory frameworks, using the (more familiar) situation in England as a point of reference. We undertook literature reviews to ascertain the legal and regulatory positions on forgoing LST in Japan, Korea, Taiwan, and England.Main textFindings from a literature review are first presented to describe the development of th

The Reversal of Immune Exclusion Mediated by Tadalafil and an Anti-tumor Vaccine Also Induces PDL1 Upregulation in Recurrent Head and Neck Squamous Cell Carcinoma: Interim Analysis of a Phase I Clinical Trial.

Myeloid Derived suppressor cells (MDSCs) play a key role in the progression and recurrence of human malignancies and in restraining the efficacy of adjuvant therapies. We have previously shown that Tadalafil lowers MDSCs and regulatory T cells (Treg) in the blood and in the tumor, primes a tumor specific immune response, and increases the number of activated intratumoral CD8+T cells in patients with primary Head and Neck Squamous Cell Carcinoma (HNSCC). However, despite these important immune modulatory actions, to date no clinically significant effects have been reported following PDE5 inhibi

Mucosal-Associated Invariant T Cells Display Diminished Effector Capacity in Oesophageal Adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is an aggressive malignancy with poor prognosis, and incidence is increasing rapidly in the Western world. Mucosal-associated invariant T (MAIT) cells recognize bacterial metabolites and kill infected cells, yet their role in OAC is unknown. We aimed to elucidate the role of MAIT cells during cancer development by characterizing the frequency, phenotype, and function of MAIT cells in human blood and tissues, from OAC and its pre-malignant inflammatory condition Barrett's oesophagus (BO). Blood and tissues were phenotyped by flow cytometry and conditioned media

Care of cancer patients at the end of life in a German university hospital: A retrospective observational study from 2014.

BackgroundCancer care including aggressive treatment procedures during the last phase of life in patients with incurable cancer has increasingly come under scrutiny, while integrating specialist palliative care at an early stage is regarded as indication for high quality end-of-life patient care.AimTo describe the demographic and clinical characteristics and the medical care provided at the end of life of cancer patients who died in a German university hospital.MethodsRetrospective cross-sectional study on the basis of anonymized hospital data for cancer patients who died in the Munich Univers

Rare Diseases of the Orbit.

This article provides an overview of rare orbital diseases. Congenital malformations, inflammatory diseases, benign and malignant neoplasias are described. Although it represents a relatively small area of the body the orbit contains multiple different tissues. Therefore, a great variety of diseases can be found within the orbital space. That is the reason, why both the completeness and the level of detail in the description of particular diseases must be somewhat limited. Nevertheless, clinical manifestations, important aspects of diagnosis, treatment strategies, and, when specific data are a

Interventions for preventing falls in older people in care facilities and hospitals.

BackgroundFalls in care facilities and hospitals are common events that cause considerable morbidity and mortality for older people. This is an update of a review first published in 2010 and updated in 2012.ObjectivesTo assess the effects of interventions designed to reduce the incidence of falls in older people in care facilities and hospitals.Search methodsWe searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (August 2017); Cochrane Central Register of Controlled Trials (2017, Issue 8); and MEDLINE, Embase, CINAHL and trial registers to August 2017.Selection crite

Challenges and Potential Solutions to Advance Global Cancer Drug Development.

Despite recent advancements in oncology drug development, patient access to innovative cancer therapies remains inadequate. There is an urgent need for more patient-centric approaches, with meaningful patient input from trial design through to health technology assessment (HTA) consultation. Multi-stakeholder consensus calls for better representation of the diversity of the target population and integration of patients' preferences in clinical cancer research by systematically collecting patient-reported outcomes using standardized methods, and acknowledging trade-offs between survival and lon

Апиген как потенциальный модулятор нейроинфламмации в многоразовом склерозе: обзор.

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы (CNS), характеризующееся нейроинфламмацией и обезвоживанием. Несмотря на то, что в течение последнего десятилетия расширились возможности лечения MS, нынешняя терапия направлена главным образом на периферийные иммунные системы и часто связана со значительными побочными эффектами. Кроме того, эта терапия до сих пор не предлагает решений для последующего нейродегенерации, сопровождающего развитие болезни. Результаты исследований, проведенных с использованием клеточных и животных моделей и исследований