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Comparison of the Efficacy of Zoledronate and Denosumab in Patients with Acute Osteoporotic Vertebral Compression Fractures: A Randomized Controlled Trial.

Background: The comparison of the efficacy of zoledronate and denosumab for treating osteoporosis is controversial, and few randomized controlled trials have compared these two drugs in practical patients with acute osteoporotic vertebral compression fractures (OVCFs). We conducted a randomized controlled study to compare the efficacy of zoledronate and denosumab in patients with acute OVCF, with a focus on the occurrence of new OVCF. Methods: We enrolled 206 subjects who had their first acute OVCF, without any previous history of osteoporosis medication. The patients were randomly assigned to

Corneal confocal microscopy to detect early immune-mediated small nerve fibre loss in AL amyloidosis.

ObjectiveLight chain (AL) amyloidosis is a life-threatening disorder characterised by extracellular deposition of amyloid leading to dysfunction of multiple organs. Peripheral nerve involvement, particularly small fibre neuropathy, may be associated with poorer survival. Corneal confocal microscopy (CCM) is a rapid and non-invasive imaging technique to quantify corneal small nerve fibres and immune cells in vivo. We aimed to evaluate CCM as a tool for early diagnosis of peripheral nerve involvement in AL amyloidosis.MethodsCCM and nerve conduction studies (NCS) were undertaken in 21 newly diag

Therapeutic effects of the novel subtype-selective histone deacetylase inhibitor chidamide on myeloma-associated bone disease.

Histone deacetylases are promising therapeutic targets in hematological malignancies. In the work herein, we investigated the effect of chidamide, a new subtype-selective histone deacetylase inhibitor that was independently produced in China, on multiple myeloma and its associated bone diseases using different models. The cytotoxicity of chidamide toward myeloma is due to its induction of cell apoptosis and cell cycle arrest by increasing the levels of caspase family proteins p21 and p27, among others. Furthermore, chidamide exhibited significant cytotoxicity against myeloma cells co-cultured

Unmasking TRALI: a case report of multiple myeloma and transfusion-associated event.

INTRODUCTION AND IMPORTANCE: Transfusion-related acute lung injury (TRALI) is a relatively rare but severe respiratory complication that can occur following the transfusion of blood products. Despite its infrequent occurrence, TRALI is a leading cause of transfusion-related mortality, underscoring the need for rapid diagnosis and appropriate management. However, diagnosis remains challenging due to its clinical overlap with other causes of acute respiratory distress syndrome (ARDS). CASE PRESENTATION: This report describes the case of a 57-year-old woman with multiple myeloma (MM) who develop

Apoptosis and (in) Pain-Potential Clinical Implications.

The deregulation of apoptosis is involved in the development of several pathologies, and recent evidence suggests that apoptosis may be involved in chronic pain, namely in neuropathic pain. Neuropathic pain is a chronic pain state caused by primary damage or dysfunction of the nervous system; however, the details of the molecular mechanisms have not yet been fully elucidated. Recently, it was found that nerve endings contain transient receptor potential (TRP) channels that sense and detect signals released by injured tissues and respond to these damage signals. TRP channels are similar to the

Gabapentinoids and unexplained death in general practice: Case series and feasibility study arising from a critical incident.

BACKGROUND: Prescribing epidemiology in general practice shows gabapentinoid drugs to be independently associated with unexpected, drug-related death. There is an increasing trend of gabapentinoid deaths throughout Europe and North America. OBJECTIVES: The overall aim of this study was to assess how patient, practice and health system factors might be associated with gabapentinoid prescribing in primary care. METHODS: Case series following a critical incident of an unexpected death in a patient prescribed a gabapentinoid drug in a single general practice. Unexpected and expected deaths in pa

Совпадение в полном тексте источника
… Most of the deaths of patients were expected and planned for in terms of a gabapentinoid drug accompanying an opiate drug use for terminal care pain relief. The majority of patients were elderly with significant multimorbidity, receiving polypharmacy drug regimes. …

Utilization of redox modulating small molecules that selectively act as pro-oxidants in cancer cells to open a therapeutic window for improving cancer therapy.

There is a rapidly growing body of literature supporting the notion that differential oxidative metabolism in cancer versus normal cells represents a metabolic frailty that can be exploited to open a therapeutic window into cancer therapy. These cancer cell-specific metabolic frailties may be amenable to manipulation with non-toxic small molecule redox active compounds traditionally thought to be antioxidants. In this review we describe the potential mechanisms and clinical applicability in cancer therapy of four small molecule redox active agents: melatonin, vitamin E, selenium, and vitamin C

Medication-Related Osteonecrosis of the Jaw (MRONJ): A Review of Pathophysiology, Risk Factors, Preventive Measures and Treatment Strategies.

Medication-related osteonecrosis of the jaw (MRONJ) is a major problem that can occur in people taking certain medications such bisphosphonates and denosumab. It can be used to treat osteoporosis or cancer. Bisphosphonate exposure, dental diseases and procedures, age, sex, anatomical factors, medical issues, and hereditary factors are all variables that enhance the risk of MRONJ. Even though MRONJ and antiresorptive medications have a close association, the pathophysiology of MRONJ is unknown. Careful dental preparation and oral hygiene instructions significantly minimize the risk of osteonecr

COVID-19 Therapeutic Options Under Investigation.

Since its emergence in China in December 2019, COVID-19 has quickly spread around the globe causing a pandemic. Vaccination or the development of herd immunity seems the only way to slow down the spread of the virus; however, both are not achievable in the near future. Therefore, effective treatments to mitigate the burden of this pandemic and reduce mortality rates are urgently needed. Preclinical and clinical studies of potential antiviral and immunomodulatory compounds and molecules to identify safe and efficacious therapeutics for COVID-19 are ongoing. Two compounds, remdesivir, and dexame

Assessing palliative care needs in adult patients with hematological malignancies and their caregivers: implications for referral practice.

BackgroundPatients with hematological malignancies frequently experience complex physical, psychological, and spiritual concerns due to disease progression and intensive therapies. Despite these needs, palliative care services are often underutilized. This study aimed to assess the palliative care needs of adult patients with hematological malignancies and their caregivers in a tertiary care setting in India.MethodsA descriptive survey was conducted from October 2022 to February 2023, involving 200 patients and their caregivers in oncology wards. The Needs Assessment Tool for Progressive Disea

Dual Roles of NIX/BNIP3L in Tumors: Friend or Foe.

Cancer is one of the leading causes of disease-related death worldwide, and targeting key regulatory genes to induce programmed cell death in tumor cells has emerged as a crucial therapeutic strategy, following surgery, radiotherapy, and chemotherapy. As a mitochondrial outer membrane protein, NIX/BNIP3L can both mediate apoptosis to inhibit tumor cell growth and promote tumor cell survival by clearing intracellular reactive oxygen species (ROS) through mitophagy. Therefore, we summarize a brief overview of the structure and function of NIX/BNIP3L, as well as the mechanisms of NIX/BNIP3L gener

Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with anakinra.

High-dose chemotherapy causes intestinal inflammation and subsequent breakdown of the mucosal barrier, permitting translocation of enteric pathogens, clinically manifesting as fever. Antibiotics are mainstay for controlling these complications, however, they are increasingly recognized for their detrimental effects, including antimicrobial resistance and dysbiosis. Here, we show that mucosal barrier injury induced by the mucotoxic chemotherapeutic agent, high-dose melphalan (HDM), is characterized by hyper-active IL-1b/CXCL1/neutrophil signaling. Inhibition of this pathway with IL-1RA, anakinr

Prognosis factors in the treatment of bisphosphonate-related osteonecrosis of the jaw - Prognostic factors in the treatment of BRONJ.

ObjectivesBisphosphonate-related osteonecrosis of the jaw (BRONJ) is a relatively rare but serious side effect of bisphosphonate (BP)-based treatments. This retrospective study aimed to investigate the risk factors and predictive markers in cases where patients were refractory to a recommended conservative treatment offered in our hospital.Patients and methodsThis single-center study collated the medical records of all patients treated for BRONJ between 2004 and 2011. A complete medical history, including detailed questionnaires, was collected for all patients, focusing on identifying underlyi

Обоснование и проектирование многоцентрового, национального, случайного, открытого испытания на этапе III: аллогенная трансплантация стволовых клеток как потенциальное лечение пациентов с повторной или прогрессирующей множественной миеломой (AlloRelapseM Study).

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Несмотря на значительные улучшения в лечении миеломы, большинство пациентов, в конечном счете, вновь вернулись к нормальной жизни или добились прогресса. Пациенты с множественной миеломой, которые вновь вернулись после начальной высокодозированной химиотерапии с аутологическими стволовыми клетками, имеют средний прогресс свободного выживания вплоть до 2-3 годы в зависимости от факторов риска, таких, как продолжительность предыдущей ремиссии. В последние годы появляется все больше данных, свидетельствующих о том, что пересадка стволовых клеток может стать перспективным ва

С-терминальный связывающий белок 2 - новый дезинфицирующий опухоль, направленный на MYC-IRF4 ось в множестве миеломы.

Клетки с множественной миеломой (MM) подвержены зависимости от MYC, а их непосредственные цели по трансактивации IRF4 направлены на распространение и выживание. MYC и IRF4 по-прежнему считаются "ненаркоманными", поскольку большинство мелких ингибиторов молекулярного происхождения страдают от низкой производительности, неоптимальных фармакокинетических свойств и нежелательных нецелевых эффектов. Косвенное подавление MYC/IRF4 проявляется в качестве терапевтической уязвимости MM. Здесь мы обнаружили неоцененную опухоль, впечатляющую роль связующего белка С-терминала 2 (CTBP2) в MM путем сильного

Multiple Myeloma-Derived Extracellular Vesicles Induce Osteoclastogenesis through the Activation of the XBP1/IRE1α Axis.

Bone disease severely affects the quality of life of over 70% of multiple myeloma (MM) patients, which daily experience pain, pathological fractures, mobility issues and an increased mortality. Recent data have highlighted the crucial role of the endoplasmic reticulum-associated unfolded protein response (UPR) in malignant transformation and tumor progression; therefore, targeting of UPR-related molecules may open novel therapeutic avenues. Endoplasmic reticulum (ER) stress and UPR pathways are constitutively activated in MM cells, which are characterized by an increased protein turnover as a

Sex-specific effects of predator scent stress on fear, anxiety-like behavior and methamphetamine seeking in rats.

UNLABELLED: Recombinant hepatitis B vaccine Engerix B((R)) [Hep-B(Eng)] is a noninfectious subunit hepatitis B viral vaccine indicated for the active immunisation of adults, children and infants against hepatitis B virus infection. It contains hepatitis B surface antigen (HBsAg) which is produced by the yeast Saccharomyces cerevisiae by use of recombinant DNA technology. In adults and children seroprotection rates [anti-HBsAg antibody (anti-HBs) titres >or=10 IU/L] were 93 to 100% 1 month after completion of the immunisation schedule with Hep-B(Eng) [0, 1, 6-month schedule]. A more rapid immun

Epigenetic Modifiers as Novel Therapeutic Targets and a Systematic Review of Clinical Studies Investigating Epigenetic Inhibitors in Head and Neck Cancer.

The survival rate of head and neck squamous cell carcinoma patients with the current standard of care therapy is suboptimal and is associated with long-term side effects. Novel therapeutics that will improve survival rates while minimizing treatment-related side effects are the focus of active investigation. Epigenetic modifications have been recognized as potential therapeutic targets in various cancer types, including head and neck cancer. This review summarizes the current knowledge on the function of important epigenetic modifiers in head and neck cancer, their clinical implications and di

Recent Advances in the Applications of Small Molecules in the Treatment of Multiple Myeloma.

Therapy for multiple myeloma (MM), a hematologic neoplasm of plasma cells, has undergone remarkable changes over the past 25 years. Small molecules (molecular weight of less than one kDa), together with newer immunotherapies that include monoclonal antibodies, antibody-drug conjugates, and most recently, chimeric antigen receptor (CAR) T-cells, have combined to double the disease's five-year survival rate to over 50% during the past few decades. Despite these advances, the disease is still considered incurable, and its treatment continues to pose substantial challenges, since therapeutic refra

Non-viral approaches in CAR-NK cell engineering: connecting natural killer cell biology and gene delivery.

Natural Killer (NK) cells are exciting candidates for cancer immunotherapy with potent innate cytotoxicity and distinct advantages over T cells for Chimeric Antigen Receptor (CAR) therapy. Concerns regarding the safety, cost, and scalability of viral vectors has ignited research into non-viral alternatives for gene delivery. This review comprehensively analyses recent advancements and challenges with non-viral genetic modification of NK cells for allogeneic CAR-NK therapies. Non-viral alternatives including electroporation and multifunctional nanoparticles are interrogated with respect to CAR