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Journal of Medicine and Life Feb 2022Many aspects make irritable bowel syndrome (IBS) challenging for both patients and physicians. The unclear pathogenesis with many pathways to be explored, bothering... (Review)
Review
Many aspects make irritable bowel syndrome (IBS) challenging for both patients and physicians. The unclear pathogenesis with many pathways to be explored, bothering symptoms that affect the quality of life, and many subtypes of the condition are only a few reasons that make IBS difficult to control and obtain satisfactory results. Treatment options start with general advice for lifestyle, continue with non-pharmaceutical treatments, and finally touch classic treatments. In this review, pharmaceutical treatment options are not accounted for. Consensus groups and meta-analyses have concluded guidelines that overall are the same, with variations in the strength of recommendations and some cultural and geographical particularities. Dietary interventions, probiotics, and fibers can be seen as non-pharmaceutical treatments that coexist in various protocols because of the relevant evidence regarding their efficacy in treating IBS symptoms.
Topics: Diet; Disaccharides; Fermentation; Humans; Irritable Bowel Syndrome; Monosaccharides; Probiotics; Quality of Life
PubMed: 35419092
DOI: 10.25122/jml-2022-0028 -
Current Problems in Cancer Feb 2022Chimeric antigen receptor-modified (CAR) T-cell therapy targeting CD19 has revolutionized the treatment of relapsed or refractory B-cell lymphomas. Based on... (Review)
Review
Chimeric antigen receptor-modified (CAR) T-cell therapy targeting CD19 has revolutionized the treatment of relapsed or refractory B-cell lymphomas. Based on unprecedented response rates and durability of response in high risk B-cell lymphoma patients, anti-CD19 CAR T-cell therapy was rapidly approved by the FDA for a variety of lymphoma subtypes. Anti-CD19 CAR T-cell therapy is now considered standard of care for patients with relapsed or refractory (R/R) aggressive non-Hodgkin's Lymphoma (NHL) after 2 or more lines of therapy. Three second-generation anti-CD19 CAR T-cell products have been FDA approved for R/R aggressive B-cell lymphoma and FDA approval has been obtained for Mantle Cell Lymphoma and Follicular lymphoma as well. This has ensured broad access to CAR T-cell therapy for patients with NHL and new real-world trials have helped confirm feasibility of CAR T-cell therapy for a broad patient population. The emergence of CAR T-cell therapy will likely provide a new patient population who is status post anti-CD19 CAR T-cell therapy. Investigation of mechanisms of failure of CAR T-cell therapy and clinical trials to study strategies to address this are thus required. Here we provide a thorough review on the use of the FDA approved anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma, and touch on mechanisms of failure of CAR T-cell therapy and potential approaches which are currently under investigation to address this.
Topics: Adult; Antigens, CD19; Humans; Immunotherapy, Adoptive; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasm Recurrence, Local
PubMed: 35012754
DOI: 10.1016/j.currproblcancer.2021.100826 -
International Journal of Molecular... Mar 2021Tryptophan is an essential amino acid critical for protein synthesis in humans that has emerged as a key player in the microbiota-gut-brain axis. It is the only... (Review)
Review
Tryptophan is an essential amino acid critical for protein synthesis in humans that has emerged as a key player in the microbiota-gut-brain axis. It is the only precursor for the neurotransmitter serotonin, which is vital for the processing of emotional regulation, hunger, sleep, and pain, as well as colonic motility and secretory activity in the gut. Tryptophan catabolites from the kynurenine degradation pathway also modulate neural activity and are active in the systemic inflammatory cascade. Additionally, tryptophan and its metabolites support the development of the central and enteric nervous systems. Accordingly, dysregulation of tryptophan metabolites plays a central role in the pathogenesis of many neurologic and psychiatric disorders. Gut microbes influence tryptophan metabolism directly and indirectly, with corresponding changes in behavior and cognition. The gut microbiome has thus garnered much attention as a therapeutic target for both neurologic and psychiatric disorders where tryptophan and its metabolites play a prominent role. In this review, we will touch upon some of these features and their involvement in health and disease.
Topics: Brain; Colon; Enteric Nervous System; Gastrointestinal Microbiome; Homeostasis; Humans; Hunger; Kynurenine; Pain; Serotonin; Sleep; Tryptophan
PubMed: 33804088
DOI: 10.3390/ijms22062973 -
Current Neuropharmacology 2020The trigeminal nerve is the largest of all cranial nerves. It has three branches that provide the main sensory innervation of the anterior two-thirds of the head and... (Review)
Review
The trigeminal nerve is the largest of all cranial nerves. It has three branches that provide the main sensory innervation of the anterior two-thirds of the head and face. Trigeminal neuralgia (TN) is characterized by sudden, severe, brief, and stabbing recurrent episodes of facial pain in one or more branches of the trigeminal nerve. Pain attacks can occur spontaneously or can be triggered by non-noxious stimuli, such as talking, eating, washing the face, brushing teeth, shaving, a light touch or even a cool breeze. In addition to pain attacks, a proportion of the patients also experience persistent background pain, which along with autonomic signs and prolonged disease duration, represent predictors of worse treatment outcomes. It is now widely accepted that the presence of a neurovascular compression at the trigeminal root entry zone is an anatomic abnormality with a high correlation with classical TN. However, TN may be related to other etiologies, thus presenting different and/or additional features. Since the 1960s, the anticonvulsant carbamazepine is the drug of choice for TN treatment. Although anti-epileptic drugs are commonly used to treat neuropathic pain in general, the efficacy of carbamazepine has been largely limited to TN. Carbamazepine, however, is associated with dose-limiting side-effects, particularly with prolonged usage. Thus, a better understanding and new treatment options are urgently warranted for this rare, but excruciating disease.
Topics: Carbamazepine; Humans; Neuralgia; Trigeminal Nerve; Trigeminal Neuralgia
PubMed: 31608834
DOI: 10.2174/1570159X17666191010094350 -
Biomedicine & Pharmacotherapy =... Mar 2022When peripheral neuropathy occurs due to chemotherapy treatment, it is referred to as chemotherapy-induced peripheral neuropathy (CIPN). Typically, symptoms are sensory... (Review)
Review
When peripheral neuropathy occurs due to chemotherapy treatment, it is referred to as chemotherapy-induced peripheral neuropathy (CIPN). Typically, symptoms are sensory rather than motor and include reduced feeling and heightened sensitivity to pressure, pain, temperature, and touch. The pathophysiology of CIPN is very complex, and it involves multiple mechanisms leading to its development which will be described specifically for each chemotherapeutic class. There are currently no approved or effective agents for CIPN prevention, and Duloxetine is the only medication that is an effective treatment against CIPN. There is an unavoidable necessity to develop preventative and treatment approaches for CIPN due to its detrimental impact on patients' lives. The purpose of this review is to examine CIPN, innovative pharmacological and nonpharmacological therapy and preventive strategies for this illness, and future perspectives for this condition and its therapies.
Topics: Analgesics; Antineoplastic Agents; Antioxidants; Complementary Therapies; Humans; Neuroprotective Agents; Patient Acuity; Peripheral Nervous System Diseases; Risk Factors; Serotonin and Noradrenaline Reuptake Inhibitors; Voltage-Gated Sodium Channel Blockers
PubMed: 35104697
DOI: 10.1016/j.biopha.2022.112671 -
Nature Nov 2020The anterolateral pathway consists of ascending spinal tracts that convey pain, temperature and touch information from the spinal cord to the brain. Projection neurons...
The anterolateral pathway consists of ascending spinal tracts that convey pain, temperature and touch information from the spinal cord to the brain. Projection neurons of the anterolateral pathway are attractive therapeutic targets for pain treatment because nociceptive signals emanating from the periphery are channelled through these spinal projection neurons en route to the brain. However, the organizational logic of the anterolateral pathway remains poorly understood. Here we show that two populations of projection neurons that express the structurally related G-protein-coupled receptors (GPCRs) TACR1 and GPR83 form parallel ascending circuit modules that cooperate to convey thermal, tactile and noxious cutaneous signals from the spinal cord to the lateral parabrachial nucleus of the pons. Within this nucleus, axons of spinoparabrachial (SPB) neurons that express Tacr1 or Gpr83 innervate distinct sets of subnuclei, and strong optogenetic stimulation of the axon terminals induces distinct escape behaviours and autonomic responses. Moreover, SPB neurons that express Gpr83 are highly sensitive to cutaneous mechanical stimuli and receive strong synaptic inputs from both high- and low-threshold primary mechanosensory neurons. Notably, the valence associated with activation of SPB neurons that express Gpr83 can be either positive or negative, depending on stimulus intensity. These findings reveal anatomically, physiologically and functionally distinct subdivisions of the SPB tract that underlie affective aspects of touch and pain.
Topics: Animals; Axons; Female; Male; Mechanotransduction, Cellular; Mice; Neural Pathways; Pain; Philosophy; Receptors, G-Protein-Coupled; Sensory Receptor Cells; Skin; Spinal Cord; Synapses; Touch
PubMed: 33116307
DOI: 10.1038/s41586-020-2860-1 -
American Journal of Physiology. Cell... Mar 2023PIEZO1 and PIEZO2 are mechanosensitive cation channels that are highly expressed in numerous tissues throughout the body and exhibit diverse, cell-specific functions in... (Review)
Review
PIEZO1 and PIEZO2 are mechanosensitive cation channels that are highly expressed in numerous tissues throughout the body and exhibit diverse, cell-specific functions in multiple organ systems. Within the musculoskeletal system, PIEZO1 functions to maintain muscle and bone mass, sense tendon stretch, and regulate senescence and apoptosis in response to mechanical stimuli within cartilage and the intervertebral disc. PIEZO2 is essential for transducing pain and touch sensations as well as proprioception in the nervous system, which can affect musculoskeletal health. PIEZO1 and PIEZO2 have been shown to act both independently as well as synergistically in different cell types. Conditions that alter PIEZO channel mechanosensitivity, such as inflammation or genetic mutations, can have drastic effects on these functions. For this reason, therapeutic approaches for PIEZO-related disease focus on altering PIEZO1 and/or PIEZO2 activity in a controlled manner, either through inhibition with small molecules, or through dietary control and supplementation to maintain a healthy cell membrane composition. Although many opportunities to better understand PIEZO1 and PIEZO2 remain, the studies summarized in this review highlight how crucial PIEZO channels are to musculoskeletal health and point to promising possible avenues for their modulation as a therapeutic target.
Topics: Cell Membrane; Ion Channels; Mechanotransduction, Cellular; Muscles; Musculoskeletal System; Humans
PubMed: 36717101
DOI: 10.1152/ajpcell.00544.2022 -
BMJ (Clinical Research Ed.) Mar 2021To describe the comparative efficacy of drug and non-drug interventions for reducing symptoms of depression in people with dementia who experience depression as a... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To describe the comparative efficacy of drug and non-drug interventions for reducing symptoms of depression in people with dementia who experience depression as a neuropsychiatric symptom of dementia or have a diagnosis of a major depressive disorder.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Medline, Embase, the Cochrane Library, CINAHL, PsycINFO, and grey literature between inception and 15 October 2020.
ELIGIBILITY CRITERIA FOR STUDY SELECTION
Randomised trials comparing drug or non-drug interventions with usual care or any other intervention targeting symptoms of depression in people with dementia.
MAIN OUTCOME MEASURES
Pairs of reviewers screened studies, abstracted aggregate level data, and appraised risk of bias with the Cochrane risk of bias tool, which facilitated the derivation of standardised mean differences and back transformed mean differences (on the Cornell scale for depression in dementia) from bayesian random effects network meta-analyses and pairwise meta-analyses.
RESULTS
Of 22 138 citations screened, 256 studies (28 483 people with dementia) were included. Missing data posed the greatest risk to review findings. In the network meta-analysis of studies including people with dementia without a diagnosis of a major depressive disorder who were experiencing symptoms of depression (213 studies; 25 177 people with dementia; between study variance 0.23), seven interventions were associated with a greater reduction in symptoms of depression compared with usual care: cognitive stimulation (mean difference -2.93, 95% credible interval -4.35 to -1.52), cognitive stimulation combined with a cholinesterase inhibitor (-11.39, -18.38 to -3.93), massage and touch therapy (-9.03, -12.28 to -5.88), multidisciplinary care (-1.98, -3.80 to -0.16), occupational therapy (-2.59, -4.70 to -0.40), exercise combined with social interaction and cognitive stimulation (-12.37, -19.01 to -5.36), and reminiscence therapy (-2.30, -3.68 to -0.93). Except for massage and touch therapy, cognitive stimulation combined with a cholinesterase inhibitor, and cognitive stimulation combined with exercise and social interaction, which were more efficacious than some drug interventions, no statistically significant difference was found in the comparative efficacy of drug and non-drug interventions for reducing symptoms of depression in people with dementia without a diagnosis of a major depressive disorder. Clinical and methodological heterogeneity precluded network meta-analysis of studies comparing the efficacy of interventions specifically for reducing symptoms of depression in people with dementia and a major depressive disorder (22 studies; 1829 patients).
CONCLUSIONS
In this systematic review, non-drug interventions were found to be more efficacious than drug interventions for reducing symptoms of depression in people with dementia without a major depressive disorder.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42017050130.
Topics: Antidepressive Agents; Cognitive Behavioral Therapy; Combined Modality Therapy; Dementia; Depression; Exercise Therapy; Humans; Network Meta-Analysis; Social Support; Therapy, Soft Tissue
PubMed: 33762262
DOI: 10.1136/bmj.n532 -
Complementary Therapies in Clinical... Aug 2022Reflexology is a complementary therapy focusing mainly on the application of pressure on the feet, hands and ears. A small but growing evidence base suggests that...
Reflexology is a complementary therapy focusing mainly on the application of pressure on the feet, hands and ears. A small but growing evidence base suggests that positive outcomes can be gained in the management and improvement of symptoms across a range of conditions. Biological plausibility is a key concept in the determination of the usefulness of therapies. Research which tests for safety and efficacy alongside the underpinning mechanism of action are therefore important. This paper explores the potential mechanism of action for the outcomes associated with reflexology treatment as reflected in the current evidence. The influences of therapeutic touch, relaxation, placebo effects and the similarities with other therapeutic methods of structural manipulation are considered. The lack of clarity around the precise definition of reflexology and the challenges of researching the therapy as a treatment tailored to individual need are discussed. A deeper understanding of the mechanism of action for reflexology may help to further develop research into safety and efficacy. Such an understanding may lead to the integration of knowledge which may provide both symptomatic support and longer term preventative health benefits.
Topics: Complementary Therapies; Ear; Foot; Hand; Humans; Massage; Musculoskeletal Manipulations; Placebo Effect; Relaxation Therapy; Therapeutic Touch
PubMed: 35613519
DOI: 10.1016/j.ctcp.2022.101606 -
Blood Sep 2023The intricate interplay of anemia and iron overload under the pathophysiological umbrella of ineffective erythropoiesis in non-transfusion-dependent β-thalassemia...
The intricate interplay of anemia and iron overload under the pathophysiological umbrella of ineffective erythropoiesis in non-transfusion-dependent β-thalassemia (NTDT) results in a complex variety of clinical phenotypes that are challenging to diagnose and manage. In this article, we use a clinical framework rooted in pathophysiology to present 4 common scenarios of patients with NTDT. Starting from practical considerations in the diagnosis of NTDT, we delineate our strategy for the longitudinal care of patients who exhibit different constellations of symptoms and complications. We highlight the use of transfusion therapy and novel agents, such as luspatercept, in the patient with anemia-related complications. We also describe our approach to chelation therapy in the patient with iron overload. Although tackling every specific complication of NTDT is beyond the scope of this article, we touch on the management of the various morbidities and multisystem manifestations of the disease.
Topics: Humans; beta-Thalassemia; Iron Chelating Agents; Thalassemia; Iron Overload; Chelation Therapy
PubMed: 37478396
DOI: 10.1182/blood.2023020683