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Journal of Hematology & Oncology Mar 2023Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While survival for younger patients over the last several decades has improved nearly sixfold... (Review)
Review
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While survival for younger patients over the last several decades has improved nearly sixfold with the optimization of intensive induction chemotherapy and allogeneic stem cell transplantation (alloHSCT), this effect has been largely mitigated in older and less fit patients as well as those with adverse-risk disease characteristics. However, the last 10 years has been marked by major advances in the molecular profiling of AML characterized by a deeper understanding of disease pathobiology and therapeutic vulnerabilities. In this regard, the classification of AML subtypes has recently evolved from a morphologic to a molecular and genetic basis, reflected by recent updates from the World Health Organization and the new International Consensus Classification system. After years of stagnation in new drug approvals for AML, there has been a rapid expansion of the armamentarium against this disease since 2017. Low-intensity induction therapy with hypomethylating agents and venetoclax has substantially improved outcomes, including in those previously considered to have a poor prognosis. Furthermore, targeted oral therapies against driver mutations in AML have been added to the repertoire. But with an accelerated increase in treatment options, several questions arise such as how to best sequence therapy, how to combine therapies, and if there is a role for maintenance therapy in those who achieve remission and cannot undergo alloHSCT. Moreover, certain subtypes of AML, such as those with TP53 mutations, still have dismal outcomes despite these recent advances, underscoring an ongoing unmet need and opportunity for translational advances. In this review, we will discuss recent updates in the classification and risk stratification of AML, explore the literature regarding low-intensity and novel oral combination therapies, and briefly highlight investigative agents currently in early clinical development for high-risk disease subtypes.
Topics: Adult; Humans; Aged; Leukemia, Myeloid, Acute; Combined Modality Therapy; Hematopoietic Stem Cell Transplantation; Mutation; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36966300
DOI: 10.1186/s13045-023-01424-6 -
Journal of Crohn's & Colitis Jan 2020
Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal; Crohn Disease; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Induction Chemotherapy; Maintenance Chemotherapy; Rectal Fistula; Severity of Illness Index
PubMed: 31711158
DOI: 10.1093/ecco-jcc/jjz180 -
American Family Physician Dec 2015Insomnia affects 10% to 30% of the population with a total cost of $92.5 to $107.5 billion annually. Short-term, chronic, and other types of insomnia are the three major... (Review)
Review
Insomnia affects 10% to 30% of the population with a total cost of $92.5 to $107.5 billion annually. Short-term, chronic, and other types of insomnia are the three major categories according to the International Classification of Sleep Disorders, 3rd ed. The criteria for diagnosis are difficulty falling asleep, difficulty staying asleep, or early awakening despite the opportunity for sleep; symptoms must be associated with impaired daytime functioning and occur at least three times per week for at least one month. Factors associated with the onset of insomnia include a personal or family history of insomnia, easy arousability, poor self-reported health, and chronic pain. Insomnia is more common in women, especially following menopause and during late pregnancy, and in older adults. A comprehensive sleep history can confirm the diagnosis. Psychiatric and medical problems, medication use, and substance abuse should be ruled out as contributing factors. Treatment of comorbid conditions alone may not resolve insomnia. Patients with movement disorders (e.g., restless legs syndrome, periodic limb movement disorder), circadian rhythm disorders, or breathing disorders (e.g., obstructive sleep apnea) must be identified and treated appropriately. Chronic insomnia is associated with cognitive difficulties, anxiety and depression, poor work performance, decreased quality of life, and increased risk of cardiovascular disease and all-cause mortality. Insomnia can be treated with nonpharmacologic and pharmacologic therapies. Nonpharmacologic therapies include sleep hygiene, cognitive behavior therapy, relaxation therapy, multicomponent therapy, and paradoxical intention. Referral to a sleep specialist may be considered for refractory cases.
Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Cognitive Behavioral Therapy; Education, Medical, Continuing; Female; Humans; Middle Aged; Practice Guidelines as Topic; Pregnancy; Relaxation Therapy; Sleep Initiation and Maintenance Disorders; United States
PubMed: 26760592
DOI: No ID Found -
Current Oncology (Toronto, Ont.) Feb 2023Multiple myeloma remains an incurable disease with the usual disease course requiring induction therapy, autologous stem cell transplantation for eligible patients, and... (Review)
Review
Multiple myeloma remains an incurable disease with the usual disease course requiring induction therapy, autologous stem cell transplantation for eligible patients, and long-term maintenance. Risk stratification tools and cytogenetic alterations help inform individualized therapeutic choices for patients in hopes of achieving long-term remissions with preserved quality of life. Unfortunately, relapses occur at different stages of the course of the disease owing to the biological heterogeneity of the disease. Addressing relapse can be complex and challenging as there are both therapy- and patient-related factors to consider. In this broad scoping review of available therapies in relapsed/refractory multiple myeloma (RRMM), we cover the pharmacologic mechanisms underlying active therapies such as immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), monoclonal antibodies (mAbs), traditional chemotherapy, and Venetoclax. We then review the clinical data supporting the use of these therapies, organized based on drug resistance/refractoriness, and the role of autologous stem cell transplant (ASCT). Approaches to special situations during relapse such as renal impairment and extramedullary disease are also covered. Lastly, we look towards the future by briefly reviewing the clinical data supporting the use of chimeric antigen receptor (CAR-T) therapy, bispecific T cell engagers (BITE), and Cereblon E3 Ligase Modulators (CELMoDs).
Topics: Humans; Multiple Myeloma; Hematopoietic Stem Cell Transplantation; Quality of Life; Transplantation, Autologous; Neoplasm Recurrence, Local
PubMed: 36826140
DOI: 10.3390/curroncol30020179 -
Planta Medica Aug 2021Sleep disorders are common among the general population and can generate health problems such as insomnia and anxiety. In addition to standard drugs and psychological... (Review)
Review
Sleep disorders are common among the general population and can generate health problems such as insomnia and anxiety. In addition to standard drugs and psychological interventions, there are different complementary plant-based therapies used to treat insomnia and anxiety. This review aimed to find and examine the most recent research on the use of herbal medicines for treating anxiety and insomnia as compiled from clinical trials, as well as to assess the safety and efficacy of these medicines and to elucidate their possible mechanisms of action. The process entailed a search of PubMed, Scopus, and the Cochrane Library databases from 2010 to 2020. The search terms included "sleep disorder", "insomnia", "sedative", "hypnotic", "anxiety", "anxiolytic", and "clinical trial", combined with the search terms "herbs" and "medicinal plants", in addition to individual herbal medicines by both their common and scientific names. This updated review, which focuses mainly on clinical trials, includes research on 23 medicinal plants and their combinations. Essential oils and their associations have also been reviewed. The efficacy of medicinal plants depends on treatment duration, types of study subjects, administration route, and treatment method. More clinical trials with an adequate, standardized design are necessary, as are more preclinical studies to continue studying the mechanisms of action. As a result of our work, we can conclude that the 3 plants with the most potential are valerian, passionflower, and ashwagandha, with the combination of valerian with hops and passionflower giving the best results in the clinical tests.
Topics: Anxiety; Anxiety Disorders; Humans; Phytotherapy; Plants, Medicinal; Sleep Initiation and Maintenance Disorders
PubMed: 34116572
DOI: 10.1055/a-1510-9826 -
The Cochrane Database of Systematic... Sep 2012Although conventional non-pharmacological and pharmacological treatments for insomnia are effective in many people, alternative therapies such as acupuncture are widely... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although conventional non-pharmacological and pharmacological treatments for insomnia are effective in many people, alternative therapies such as acupuncture are widely practised. However, it remains unclear whether current evidence is rigorous enough to support acupuncture for the treatment of insomnia.
OBJECTIVES
To determine the efficacy and safety of acupuncture for insomnia.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, Dissertation Abstracts International, CINAHL, AMED, the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS), the World Health Organization (WHO) Trials Portal (ICTRP) and relevant specialised registers of the Cochrane Collaboration in October 2011. We screened reference lists of all eligible reports and contacted trial authors and experts in the field.
SELECTION CRITERIA
Randomised controlled trials evaluating any form of acupuncture for insomnia. They compared acupuncture with/without additional treatment against placebo or sham or no treatment or same additional treatment. We excluded trials that compared different acupuncture methods or acupuncture against other treatments.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias. We used odds ratio (OR) and mean difference for binary and continuous outcomes respectively. We combined data in meta-analyses where appropriate.
MAIN RESULTS
Thirty-three trials were included. They recruited 2293 participants with insomnia, aged 15 to 98 years, some with medical conditions contributing to insomnia (stroke, end-stage renal disease, perimenopause, pregnancy, psychiatric diseases). They evaluated needle acupuncture, electroacupuncture, acupressure or magnetic acupressure.Compared with no treatment (two studies, 280 participants) or sham/placebo (two studies, 112 participants), acupressure resulted in more people with improvement in sleep quality (compared to no treatment: OR 13.08, 95% confidence interval (CI) 1.79 to 95.59; compared to sham/placebo: OR 6.62, 95% CI 1.78 to 24.55). However, when assuming that dropouts had a worse outcome in sensitivity analysis the beneficial effect of acupuncture was inconclusive. Compared with other treatment alone, acupuncture as an adjunct to other treatment might marginally increase the proportion of people with improved sleep quality (13 studies, 883 participants, OR 3.08, 95% CI 1.93 to 4.90). On subgroup analysis, only needle acupuncture but not electroacupuncture showed benefits. All trials had high risk of bias and were heterogeneous in the definition of insomnia, participant characteristics, acupoints and treatment regimen. The effect sizes were generally small with wide confidence intervals. Publication bias was likely present. Adverse effects were rarely reported and they were minor.
AUTHORS' CONCLUSIONS
Due to poor methodological quality, high levels of heterogeneity and publication bias, the current evidence is not sufficiently rigorous to support or refute acupuncture for treating insomnia. Larger high-quality clinical trials are required.
Topics: Acupressure; Acupuncture Therapy; Humans; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders
PubMed: 22972087
DOI: 10.1002/14651858.CD005472.pub3 -
Frontiers in Immunology 2018Dendritic cells (DC) are professional antigen presenting cells, uniquely able to induce naïve T cell activation and effector differentiation. They are, likewise,... (Review)
Review
Dendritic cells (DC) are professional antigen presenting cells, uniquely able to induce naïve T cell activation and effector differentiation. They are, likewise, involved in the induction and maintenance of immune tolerance in homeostatic conditions. Their phenotypic and functional heterogeneity points to their great plasticity and ability to modulate, according to their microenvironment, the acquired immune response and, at the same time, makes their precise classification complex and frequently subject to reviews and improvement. This review will present general aspects of the DC physiology and classification and will address their potential and actual uses in the management of human disease, more specifically cancer, as therapeutic and monitoring tools. New combination treatments with the participation of DC will be also discussed.
Topics: Animals; Biomarkers; Cancer Vaccines; Cell Differentiation; Combined Modality Therapy; Dendritic Cells; Humans; Immune System; Immune System Phenomena; Immunotherapy; Neoplasms; Phenotype; Treatment Outcome; Tumor Microenvironment
PubMed: 30719026
DOI: 10.3389/fimmu.2018.03176 -
Journal of Cardiac Failure Mar 2023Vericiguat is a soluble guanylate cyclase stimulator approved by multiple global regulatory bodies and recommended in recently updated clinical practice guidelines to... (Review)
Review
Vericiguat is a soluble guanylate cyclase stimulator approved by multiple global regulatory bodies and recommended in recently updated clinical practice guidelines to reduce morbidity and mortality in patients with worsening chronic heart failure (HF) with reduced ejection fraction (HFrEF). Despite the growing armaments of evidence-based medical therapy for HFrEF that have demonstrated clinical outcome benefits, there is a need to address residual risk following worsening HF events. When considering therapies aimed to mitigate postevent cardiovascular risk, potential barriers preventing the prescription of vericiguat in eligible patients may include providers' lack of familiarity with it, clinical inertia, limited knowledge about monitoring response to therapy, and concerns about potential adverse effects as well as integration of its routine use during an era of in-person and telehealth hybrid ambulatory care. This review provides an overview of vericiguat therapy and proposes an evidence-based and practical guidance strategy toward implementing its use in various clinical settings. This review additionally summarizes patient counseling points for its initiation and maintenance.
Topics: Humans; Heart Failure; Treatment Outcome; Stroke Volume; Patient Care
PubMed: 36529314
DOI: 10.1016/j.cardfail.2022.10.431 -
Expert Opinion on Therapeutic Targets Jul 2017Currently the treatment of chronic pain is inadequate and compromised by debilitating central nervous system side effects. Here we discuss new therapeutic strategies... (Review)
Review
Currently the treatment of chronic pain is inadequate and compromised by debilitating central nervous system side effects. Here we discuss new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and safer treatment of chronic pain. Areas covered: The DRGs contain the cell bodies of primary sensory neurons including nociceptive neurons. After painful injuries, primary sensory neurons demonstrate maladaptive molecular changes in DRG cell bodies and in their axons. These changes result in hypersensitivity and hyperexcitability of sensory neurons (peripheral sensitization) and are crucial for the onset and maintenance of chronic pain. We discuss the following new strategies to target DRGs and primary sensory neurons as a means of alleviating chronic pain and minimizing side effects: inhibition of sensory neuron-expressing ion channels such as TRPA1, TRPV1, and Nav1.7, selective blockade of C- and Aβ-afferent fibers, gene therapy, and implantation of bone marrow stem cells. Expert opinion: These peripheral pharmacological treatments, as well as gene and cell therapies, aimed at DRG tissues and primary sensory neurons can offer better and safer treatments for inflammatory, neuropathic, cancer, and other chronic pain states.
Topics: Analgesics; Animals; Bone Marrow Transplantation; Cell- and Tissue-Based Therapy; Chronic Pain; Ganglia, Spinal; Genetic Therapy; Humans; Sensory Receptor Cells
PubMed: 28480765
DOI: 10.1080/14728222.2017.1328057 -
BMC Nephrology Aug 2016Fluid overload is frequently found in acute kidney injury patients in critical care units. Recent studies have shown the relationship of fluid overload with adverse... (Review)
Review
BACKGROUND
Fluid overload is frequently found in acute kidney injury patients in critical care units. Recent studies have shown the relationship of fluid overload with adverse outcomes; hence, manage and optimization of fluid balance becomes a central component of the management of critically ill patients.
DISCUSSION
In critically ill patients, in order to restore cardiac output, systemic blood pressure and renal perfusion an adequate fluid resuscitation is essential. Achieving an appropriate level of volume management requires knowledge of the underlying pathophysiology, evaluation of volume status, and selection of appropriate solution for volume repletion, and maintenance and modulation of the tissue perfusion. Numerous recent studies have established a correlation between fluid overload and mortality in critically ill patients. Fluid overload recognition and assessment requires an accurate documentation of intakes and outputs; yet, there is a wide difference in how it is evaluated, reviewed and utilized. Accurate volume status evaluation is essential for appropriate therapy since errors of volume evaluation can result in either in lack of essential treatment or unnecessary fluid administration, and both scenarios are associated with increased mortality. There are several methods to evaluate fluid status; however, most of the tests currently used are fairly inaccurate. Diuretics, especially loop diuretics, remain a valid therapeutic alternative. Fluid overload refractory to medical therapy requires the application of extracorporeal therapies. In critically ill patients, fluid overload is related to increased mortality and also lead to several complications like pulmonary edema, cardiac failure, delayed wound healing, tissue breakdown, and impaired bowel function. Therefore, the evaluation of volume status is crucial in the early management of critically ill patients. Diuretics are frequently used as an initial therapy; however, due to their limited effectiveness the use of continuous renal replacement techniques are often required for fluid overload treatment. Successful fluid overload treatment depends on precise assessment of individual volume status, understanding the principles of fluid management with ultrafiltration, and clear treatment goals.
Topics: Acute Kidney Injury; Body Fluids; Critical Care; Critical Illness; Disease Management; Fluid Therapy; Humans; Intensive Care Units; Renal Replacement Therapy
PubMed: 27484681
DOI: 10.1186/s12882-016-0323-6