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NDP52 и его новая роль в патогенезе.

Автофагика - это процесс, способствующий выживанию, который регулирует деградацию и обновление клеточных компонентов, что делает его важнейшим механизмом для клеточного гомеостазиза. Существуют выборочные формы автофагии, характерные для ряда субстратов, таких, как патогены (бактерии или вирусы), белковые агрегаты или излишние/поврежденные органеллы. Эти процессы включают в себя в качестве ключевых игроков автофагичные рецепторы, которые связывают груз, подлежащий деградации, с автофагическим оборудованием. Среди них NDP52 (известный также как КАКПО2) был охарактеризован как «бридж» между авто

Advanced Therapy Medicinal Products: Availability, Access and Expenditure in Italy.

BackgroundAdvanced therapy medicinal products (ATMPs) are an innovative output of biomedical research, characterized by a high level of uncertainty on long-term efficacy and safety, elevated price tags and often complex administration. All these elements compounded make their European authorization, national price negotiation for reimbursement and subsequent dispensation and administration to the patient less straightforward and often less successful than for less innovative drugs. To assess if these hurdles have affected patient access and how are ATMPs used in Italy, we have analysed availab

Multiple myeloma: unplanned diagnostic pathways and association with risk factors and survival - a nationwide register-based cohort study in Denmark.

BackgroundMultiple myeloma often presents with vague and non-specific symptoms. Many patients are diagnosed in unplanned rather than elective (planned) diagnostic pathways. This study investigates the diagnosis of multiple myeloma in unplanned pathways and the association with patient characteristics, disease profile, and survival.MethodsWe conducted a nationwide register-based study, including all patients diagnosed with multiple myeloma in Denmark in 2014-2018. Patients were categorised as diagnosed in an unplanned pathway if registered with an acute admission within 30 days prior to the mul

Impact of venous thromboembolism on the mortality in patients with cancer: a population-based cohort study.

BackgroundDespite recent improvements in the treatment of cancer, little is known about the long-term survival in patients with cancer and venous thromboembolism. We aimed to examine the five-year mortality of venous thromboembolism in cancer patients in a large population-based cohort study.MethodsUsing Danish healthcare registries from 1995 to 2020, we obtained data on cancer patients with venous thromboembolism and comparison cohorts of cancer patients without venous thromboembolism, matched in terms of cancer type, age, sex, and year of cancer diagnosis, and adjusted for level of comorbidi

Consensus on the Treatment and Follow-Up for Metastatic Castration-Resistant Prostate Cancer: A Report From the First Global Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

PurposeTo present a summary of the recommendations for the treatment and follow-up for metastatic castration-resistant prostate cancer (mCRPC) as acquired through a questionnaire administered to 99 physicians working in the field of prostate cancer in developing countries who attended the Prostate Cancer Consensus Conference for Developing Countries.MethodsA total of 106 questions out of more than 300 questions addressed the use of imaging in staging mCRPC, treatment recommendations across availability and response to prior drug treatments, appropriate drug treatments, and follow-up, and those

Chemotherapy-based versus chemotherapy-free stem cell mobilization (± plerixafor) in multiple myeloma patients: an Italian cost-effectiveness analysis.

Given the availability and efficacy of the mobilizing agent plerixafor in augmenting hematopoietic progenitor cell mobilization with granulocyte colony-stimulating factor (G-CSF), there is a strong case for comparing the cost-effectiveness of mobilization with G-CSF + cyclophosphamide versus G-CSF alone. This study investigated the cost and effectiveness (i.e., successful 4 million-CD34+ collection) of G-CSF alone versus high-dose cyclophosphamide (4 g/m2) + G-CSF mobilization (± on-demand plerixafor) in patients with multiple myeloma (MM) eligible for autograft in Italy. A decision tree-suppo

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… The loss of working hours was valued using the gross wage rate (i.e., net wage + income taxes + social security contributions; Table S13 ) [ 39 – 41 ]. …

Cost-effectiveness of Novel Treatment Sequences for Transplant-Ineligible Patients With Multiple Myeloma.

ImportanceAlthough the number of treatments for elderly patients with non-transplant-eligible (NTE) multiple myeloma (MM) has increased substantially, evidence is lacking on the clinical effectiveness and cost-effectiveness of novel treatment sequences.ObjectiveTo determine the optimal sequence of treatment for patients with NTE MM from the perspective of the patient, physician, and society.Design, setting, and participantsUsing data from a Dutch observational registry, this economic evaluation combined evidence from network meta-analyses in a patient-level simulation model and modeled time-to

Orchestrating an immune response against cancer with engineered immune cells expressing αβTCRs, CARs, and innate immune receptors: an immunological and regulatory challenge.

Over half a century ago, the first allogeneic stem cell transplantation (allo-SCT) initiated cellular immunotherapy. For several decades, little progress was made, and toxicity of allo-SCT remained a major challenge. However, recent breakthroughs have opened new avenues to further develop this modality and to provide less toxic and equally efficient interventions for patients suffering from hematological or solid malignancies. Current novel cellular immune interventions include ex vivo expansion and adoptive transfer of tumor-infiltrating immune cells or administration of drugs which antagoniz

Cost-effectiveness Analysis of Nutrition Facts Added-Sugar Labeling and Obesity-Associated Cancer Rates in the US.

ImportanceObesity-associated cancer burdens are increasing in the US. Nutrition policies, such as the Nutrition Facts added-sugar labeling, may reduce obesity-associated cancer rates.ObjectiveTo evaluate the cost-effectiveness of Nutrition Facts added-sugar labeling and obesity-associated cancer rates in the US.Design, setting, and participantsA probabilistic cohort state-transition model was used to conduct an economic evaluation of added-sugar labeling and 13 obesity-associated cancers among 235 million adults aged 20 years or older by age, sex, and race/ethnicity over a median follow-up of

The PRO-CAR-T™ study: achieving excellence in patient and public involvement and engagement.

BackgroundPatient and Public Involvement and Engagement (PPIE) is advocated in Patient Reported Outcome (PRO) research, but implementation remains inconsistent and often suboptimal. Many barriers exist, including a lack of understanding about how to apply the principles of PPIE in practice. This paper offers an example of how PPIE can be meaningfully integrated into the development of a digital PRO system within the complex and rapidly evolving field of advanced therapies. The aims are to offer practical insights about how PPIE was conceptualised and operationalised in the context of this stud

The Persistence of Stigma and Other Challenges Experienced by Medical Cannabis Users: A Thematic Synthesis of Qualitative Studies.

BackgroundThe legislation, practices, and guidance shaping patient and professional access to medical cannabis (MC) for managing chronic pain and other conditions vary widely across jurisdictions. Despite promising evidence of effectiveness, challenges persist for those trying to access or prescribe MC. Little is known about how patients navigate these complex environments. We aimed to understand the evidence related to personal lived experiences associated with using MC for chronic pain and other conditions in negotiating these challenges.SummaryWe used a framework by Thomas and Harden for co

Burden of Disease and Cost of Illness of Overweight and Obesity in Portugal.

IntroductionThe prevalence of overweight and obesity has increased in the last decades, posing significant health and economic impacts globally. These conditions are related to several non-communicable diseases, including cardiovascular disease, type II diabetes, and cancer. This study estimated the disease burden and healthcare costs associated with overweight and obesity in the adult population in mainland Portugal, in 2018.MethodBurden of disease was measured in disability-adjusted life years (DALYs) following Global Burden of Disease (GBD) methodology. DALYs were calculated as the sum of y

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… The World Health Organisation has published an overview of “best-buy” strategies including community public education and awareness for physical activity and taxes on sugar-sweetened beverages and front-of-package labelling [ 58 ]. …

Financial challenges of being on long-term, high-cost medications.

The isocitrate dehydrogenase (IDH) inhibitor, vorasidenib, may offer a promising new treatment option for patients with IDH-mutant gliomas. However, the indefinite nature of this targeted therapy raises significant financial concerns. High costs of targeted cancer therapies, often exceeding $150 000 annually, contribute to financial toxicity, characterized by medical debt, income loss, and psychological stress, and place stress on health systems. This review analyzes the drug approval and pricing mechanisms in various countries and their impact on healthcare costs and patient access, focusing

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… The high costs of medications can place a strain on the system, which can translate into increased premiums (and/or taxes) for residents, or redistribution of other finite healthcare resources. …

Oral foci of infection and their relationship with hospital stay after haematopoietic cell transplantation.

PurposeOral focus screening is recommended before HCT (haematopoietic cell transplantation). Acute foci are generally treated pre-HCT. However, it is unclear whether chronic foci should be treated pre-HCT. This study aimed to evaluate the association between number of foci and early post-HCT morbidity and mortality.MethodsPatients who received an oral screening pre-HCT at Radboudumc between 2013 and 2023, with a recent panoramic radiograph, were included. Foci were defined as teeth or implants with deep pockets, furcation radiolucencies, periapical radiolucencies, deep caries, partial eruption

High-Dose Intravenous Vitamin C Combined with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase II Trial.

UNLABELLED: High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event r

Attitudinal, regional and sex related vulnerabilities to COVID-19: Considerations for early flattening of curve in Nigeria.

Background: In Nigeria, the policies and interventions due to the COVID-19 pandemic are majorly directed at businesses and relief. There are no clear plans to identify individuals with comorbidities associated with high morbidity and fatality rates. This paper identifies comorbidities associated with high morbidity and fatalities of COVID-19 across countries and vulnerable groups in Nigeria. Methods: Peer-reviewed articles published between 2010 and 2020 retrieved from Google scholar, African Journal Online, EMBASE, Scopus, and MEDLINE/PubMed (central) were systematically reviewed. Results: Th

Contribution of Macrophages and T Cells in Skeletal Metastasis.

Bone is a common site for metastases with a local microenvironment that is highly conducive for tumor establishment and growth. The bone marrow is replete with myeloid and lymphoid linage cells that provide a fertile niche for metastatic cancer cells promoting their survival and growth. Here, we discuss the role of macrophages and T cells in pro- and anti-tumoral mechanisms, their interaction to support cancer cell growth, and their contribution to the development of skeletal metastases. Importantly, immunotherapeutic strategies targeting macrophages and T cells in cancer are also discussed in

Medicine manipulation: An alternative to mitigate therapeutic gaps in the Brazilian Unified Health System?

Despite the various initiatives carried out in Brazil and in the world, the challenge of offering essential medicines in adequate presentations remains, especially to the public affected by diseases considered neglected and the pediatric population, for whom the therapeutic options remain limited. The main objective of this study was to evaluate the production of manipulated medicines as a strategy to mitigate therapeutic and access gaps to essential medicines within the Brazilian public health system, called the Unified Health System (SUS). The evaluation, carried out between 2020 and 2021, i

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… For this study, neither the cost of taxes nor the cost of sales were added, which generally takes into account different factors, such as the consuming public, competition and the market, generally marked by the multiplication of the cost price of the raw material and packaging for a profitability value …

Molecular mechanisms of the preventable causes of cancer in the United States.

Annually, there are 1.6 million new cases of cancer and nearly 600,000 cancer deaths in the United States alone. The public health burden associated with these numbers has motivated enormous research efforts into understanding the root causes of cancer. These efforts have led to the recognition that between 40% and 45% of cancers are associated with preventable risk factors and, importantly, have identified specific molecular mechanisms by which these exposures modify human physiology to induce or promote cancer. The increasingly refined knowledge of these mechanisms, which we summarize here,

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… Success depends on a comprehensive tobacco control program that includes a combination of evidence-based policies (e.g., raising tobacco taxes and smoke-free air policies), public educational campaigns, and programs to prevent smoking uptake and aid cessation (The Community Guide, https://www.thecommunityguide.org … Presumably, as with smoking, the most effective approach would be to make the desired behavior the only or the easiest choice; for example, by banning or heavily taxing foods such as large sugary drinks ( https://www.theguardian.com/society/2017/feb/2022/mexico-sugar-tax-lower-consumption-second-year-running …

Rare disease patients protection: theoretical discussion and institutional construction of orphan drug designation in China.

Orphan drugs play a vital role, often described as the "public goods of public goods." As a result, they demand robust policy support. Among these, the designation of orphan drugs serves as the pivotal and core element of the national incentive mechanism for such drugs. The designation of orphan drugs is a prerequisite and a key system to determine whether pharmaceutical enterprises are eligible to access policy support, which directly determines the effective output of orphan drugs and the fairness of public policies. However, there is still an urgent need to explore this system in China theo