Chronic Phase Research Articles

Impact of Pemphigus on Sleep Quality: A Prospective Observational Single-Center Case-Control Study.

Pemphigus, an autoimmune disorder, significantly impacts the quality of life for those affected. This study examined the sleep quality in patients with pemphigus, a domain for which the existing literature provides limited data without a focused analysis. A total of 156 individuals, 52 in the case and 104 in the control group, completed several questionnaires (Pittsburgh Sleep Quality Index [PSQI], General Health Questionnaire-12 [GHQ-12], and ABQOL [Autoimmune Bullous Disease Quality of Life]). Disease severity was evaluated using the Pemphigus disease area index (PDAI index). The case group exhibited significantly higher levels of psychological distress, reflected in GHQ-12 scores (P = 0.00), and notably poorer sleep quality compared to controls across various parameters (sleep latency [SL], disturbances [SDi], medication [SM], daytime sleep dysfunction [DSD]), and the global PSQI score (GS)] (P = 0.00)). Significant correlations were observed between PDAI scores and sleep duration (SDu) (P = 0.01), SM (P=0.03), SL (P =0.03), and GS (P=0.00). An association was found between the equivalent steroid intake and SDu (P=0.00) as well as GS (P=0.02). No statistically significant correlation emerged between disease duration and PSQI scores. Our findings indicated a correlation between poor sleep quality and cutaneous rather than mucosal manifestations (p=0.01). Pemphigus affects sleep quality. Severe disease showed heightened SDi, correlating with higher steroid doses, and in the chronic phase, the impact seems to have been more influenced by the pro-inflammatory stage of the disease. Patients with cutaneous pemphigus exhibited reduced sleep quality compared to those with oral pemphigus. Understanding that pemphigus worsens sleep quality can be beneficial for the holistic management of individuals with this condition.

A Recent Advance in the Diagnosis, Treatment, and Vaccine Development for Human Schistosomiasis.

Schistosomiasis, which affects a large number of people worldwide, is among the most overlooked parasitic diseases. The disease is mainly prevalent in sub-Saharan Africa, southeast Asian countries, and South America due to the lack of adequate sanitation. The disease is mainly associated with poor hygiene, sanitation, and contaminated water, so it is also known as a disease of poverty. Three Schistosoma species (S. mansoni, S. japonicum, and S. haematobium) cause significant human infections. Co-infections with Schistosoma and other parasites are widely common. All these parasites may cause intestinal or urogenital schistosomiasis, where the disease may be categorized into the acute, sensitized, and chronic phases. The disease is more prevalent among school children, which may cause anemia and reduce development. Chronic infections frequently cause significant liver, intestinal, and bladder damage. Women exposed to contaminated water while performing normal duties like washing clothes might acquire urogenital schistosomiasis (UGS), which can cause tissue damage and raise the risk of blood-borne disease transmission, including human immunodeficiency virus (HIV) transmission. Praziquantel (PZQ) is the World Health Organization (WHO)-prescribed treatment for individuals who are known to be infected, but it does not prevent further re-infections with larval worms. Vaccine development and new molecular-based diagnosis techniques have promised to be a reliable approach to the diagnosis and prevention of schistosomiasis. The current review emphasizes the recent advancement in the diagnosis of schistosomiasis by molecular techniques and the treatment of schistosomiasis by combined and alternative regimes of drugs. Moreover, this review has also focused on the recent outbreak of schistosomiasis, the development of vaccines, and their clinical trials.

Cardiac Arrhythmias and Autonomic Dysfunction Associated With COVID-19: A Scientific Statement From the American Heart Association.

Cardiac arrhythmias are commonly noted in patients during infections with and recovery from COVID-19. Arrhythmic manifestations span the spectrum of innocuous and benign to life-threatening and deadly. Various pathophysiological mechanisms have been proposed. Debate continues on the impact of incident and exacerbated arrhythmias on the acute and chronic (recovery) phase of the illness. COVID-19 and COVID-19 vaccine-associated myocardial inflammation and autonomic disruption remain concerns. As the pandemic has transformed to an endemic, with discovery of new SARS-CoV-2 variants, updated vaccines, and potent antiviral drugs, vigilance for COVID-19-associated arrhythmic and dysautonomic manifestations remains. The objective of this American Heart Association scientific statement is to review the available evidence on the epidemiology, pathophysiology, clinical presentation, and management of cardiac arrhythmias and autonomic dysfunction in patients infected with and recovering from COVID-19 and to provide evidence-based guidance. The writing committee's consensus on implications for clinical practice, gaps in knowledge, and directions for future research are highlighted.

Granulocyte colony-stimulating factor protects against arthritogenic alphavirus pathogenesis in a type I IFN-dependent manner.

Arthritogenic alphaviruses cause disease characterized by fever, rash, and incapacitating joint pain. Alphavirus infection stimulates robust inflammatory responses in infected hosts, leading to the upregulation of several cytokines, including granulocyte colony-stimulating factor (G-CSF). G-CSF is secreted by endothelial cells, fibroblasts, macrophages, and monocytes and binds to colony stimulating factor 3 receptor (CSF3R, also known as G-CSFR) on the surface of myeloid cells. G-CSFR signaling initiates proliferation, differentiation, and maturation of myeloid cells, especially neutrophils. Importantly, G-CSF has been found at high levels in both the acute and chronic phases of chikungunya disease; however, the role of G-CSF in arthritogenic alphavirus disease remains unexplored. Here, we sought to test the effect of G-CSF on chikungunya virus (CHIKV) and Mayaro virus (MAYV) infection using G-CSFR-deficient mice (G-CSFR-/-). We observed sustained weight loss in G-CSFR-/- mice following viand MAYV infection compared to wild-type mice. Furthermore, G-CSFR-/- mice had a significantly higher percentage of inflammatory monocytes and reduction in neutrophils throughout infection. The difference in weight loss in G-CSFR-/- mice induced by alphavirus infection was corrected by blocking type I IFN signaling. In summary, these studies show that type I IFN signaling contributes to G-CSFR mediated control of arthritogenic alphavirus disease.

SACR EPIDEMIC MODEL FOR THE SPREAD OF HEPATITIS B DISEASE BY CONSIDERING VERTICAL TRANSMISSION

Hepatitis B is an infectious disease that causes inflammation of the liver due to infection with the Hepatitis B virus. Hepatitis B is divided into two phases: the acute phase and the chronic phase. Hepatitis B virus (HBV) can be prevented through vaccination and treatment of susceptible and infected individuals. The spread of the virus can be modeled using mathematical modeling of epidemics. In this study, the model used consists of four classes, namely vulnerable individuals (S), acute individuals (A), chronic individuals (C), and recovered individuals (R). The purpose of this study is to explain the formation of the Hepatitis B disease epidemic model, analyze the stability of the model, perform simulations, and conduct parameter sensitivity analysis on the basic reproductive number. The result of this study is the construction of an epidemic model of the spread of hepatitis B disease in the form of a SACR model. This model takes into account the transmission that occurs not only through interactions between susceptible individuals and chronic individuals but also through the birth process, which occurs in chronic subpopulations because babies born can be chronically infected (vertical transmission from mother to baby). The model produces two equilibrium points, the disease-free equilibrium and the endemic equilibrium. Both points were analyzed for stability using the linearization method and were found to be asymptotically stable. Furthermore, the model simulation was carried out using the fourth-order Runge-Kutta method and sensitivity analysis of the basic reproduction number. From the results obtained, it can be concluded that the spread of hepatitis B disease can be minimized by reducing contact between susceptible and chronic individuals, increasing treatment of chronic individuals, and increasing the number of vaccinated individuals in susceptible populations.

The effectiveness of massage gun treatment combined with passive stretching in reducing non-specific lower back pain

Non-specific lower back pain is a common condition characterized by strain, muscle spasms, or weakness of the paraspinal muscles, particularly the multifidus muscle, which affects adjacent musculature such as the gluteus, hamstrings, and quadriceps. This study aimed to investigate whether massage gun treatment combined with passive stretching could reduce non-specific low back pain in patients experiencing subacute and chronic phases of this condition. This pseudo-experimental research employed a one-group pretest-posttest design with three treatments. Participants were selected using purposive sampling based on inclusion criteria: suffering from non-specific low back pain, willingness to participate, and age between 20 and 65 years. Exclusion criteria included anatomical abnormalities of the spine, fractures, open wounds, and specific spinal disorders. The visual analog scale (VAS) was used to measure pain intensity before and after each treatment session. Initial VAS scores averaged 65.6 units. Following the first treatment, scores decreased significantly to 52.1 units; subsequent reductions occurred at 42.1 units post-second treatment and 33.5 units post-third treatment. Statistical analysis revealed a significant difference across all three treatment sessions (p = 0.000 0.05), indicating a progressive improvement in pain control over time. Massage gun therapy coupled with passive stretching demonstrated efficacy in reducing non-specific lower back pain among participants. These findings suggest that repeated application of these interventions can lead to sustained improvements in pain management for individuals suffering from subacute and chronic non-specific low back pain conditions

Different expression patterns of inflammation-related genes and serum microRNAs in young-onset ischemic stroke

Brain ischemia results in the activation of a cascade of inflammatory responses, contributing to the pathogenesis of stroke. This study aimed to assess the patterns of possible changes in the expression of specific inflammation-associated protein-encoding genes and miRNAs in the peripheral blood between the acute and chronic phase of young-onset cryptogenic (Cryp) and large-artery atherosclerotic (LAA) stroke. Blood and serum were collected from patients with cryptogenic and large-artery atherosclerotic stroke at the stroke onset and 1-year follow-up. The relative expression of inflammation-related genes was analysed at the mRNA and miRNA levels using real-time quantitative PCR. Moreover, the relationship between the relative gene expression levels and clinical data was assessed using several different statistical approaches. Seventy-three patients were included in this study, with a median age of 47 (IQR, 9) years. Approximately 72% were men. In patients with cryptogenic stroke, at the mRNA level, ICAM1, CXCL8, TNF, NFKBIA, PYCARD, IL1B, and IL18 were observed to be upregulated at the stroke onset compared to the 1-year follow-up. In patients with LAA stroke, only the expression of NFKBIA was significantly higher during acute stroke. Further, the miRNA serum levels of miR-21, miR-122, and miR-155 were higher at the onset of stroke in patients with cryptogenic stroke but not in those with LAA stroke. The differences between the relative gene expression levels during acute stroke and at the 1-year follow-up were more pronounced in patients with cryptogenic stroke with no cardiovascular risk factors. The expression changes of inflammatory genes in whole blood and miRNAs in the serum differ in patients with cryptogenic and LAA stroke.

EEG synchronization patterns during a Go/No-Go task in individuals with aphasia in subacute and chronic phases of stroke

Stroke and subsequent neuroregenerative processes cause changes in neural organization of attentional functions. In this study, we attempted to identify differences in neural synchronization patterns during a visual Go/No-Go task in people with post-stroke aphasia in both subacute and chronic stroke phases. To identify neuronal underpinnings of the behavioral differences we investigated pairwise connectivity patterns using corrected imaginary phase locking value and graph-theoretic measures (efficiency, modularity and clustering coefficient) at global and local level in subacute (n = 13) and chronic stroke phases (n = 14) during a Go/No-Go task. We observed significantly lower phase synchronization in the Subacute Group in the alpha band in the connections spanning frontal and central areas of both hemispheres alongside lower local efficiency and clustering coefficient in the left frontal region. Additionally, we observed higher modularity in the beta band in the unaffected right parietal region in the Subacute Group which may denote inhibition of motor and attention functions. Those mechanisms could serve to align cognitive abilities between the damaged and healthy hemispheres, harmonizing the activity of the neuronal networks of both hemispheres disrupted by the effects of the stroke. Our findings have potential implications for rehabilitation therapies, which should take into account the pattern of connectivity changes during different phases of reovery.

Dose-escalation of second-line and first-line asciminib in chronic myeloid leukemia in chronic phase: the ASC2ESCALATE Phase IItrial.

Up to 40% of newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) discontinue treatment by 5 years, primarily due to resistance or intolerance. Rates of resistance to second-line (2L) treatment are also high. Some patients with resistance respond with dose escalation of tyrosine kinase inhibitors (TKIs). Asciminib demonstrated safety and efficacy across a broad dosage range. ASC2ESCALATE is an ongoing, Phase II, multicenter, single-arm, dose-escalation study of asciminib in 2L and first-line treatment of CML-CP. The primary end point is major molecular response at 12months in 2L. Secondary end points include molecular responses at and by scheduled time points, survival, and safety. ASC2ESCALATE is the first study investigating asciminib in CML-CP following failure of one prior TKI.Clinical Trial Registration: NCT05384587 (ClinicalTrials.gov).

Assessment of Alinity s Chagas® as a Primary Diagnostic Test for Chronic Chagas Disease in a Non-Endemic Area of Europe (Barcelona, Spain).

Chagas disease (CD) has become a worldwide problem due to globalization. In Europe, most cases are imported and are diagnosed in the chronic phase by two serological tests, as recommended by the World Health Organization. Chemiluminescent microparticle immunoassays (CMIAs) are an emerging alternative to the diagnostic standard. We aimed to validate the CMIA Alinity s Chagas® as a primary diagnostic test for chronic CD following its replacement of Architect Chagas®, with an amended signal-to-cut-off (S/CO) ratio of ≥6. Laboratory results and clinical data were collected retrospectively from 774 sera from an at-risk population tested for CD in Barcelona during 2020-2022. Negative results required no further testing, and those with a S/CO ratio ≥ 0.8 were confirmed by a second serological assay, according to the common practice. Four per cent of the samples (31/774) were determined to be seropositive by Alinity s, 93.5% of which (29/31) had an S/CO ratio ≥ 6. Almost all the samples could be directly classified by the corrected S/CO. Alinity s Chagas® was validated as a single test for chronic CD diagnosis by raising the S/CO to ≥6. Its implementation could provide faster results and help reduce CD underdiagnosis in non-endemic countries.

Glutamine Oxidation in Mouse Dorsal Root Ganglia Regulates Pain Resolution and Chronification.

Chronic pain remains a significant health challenge with limited effective treatments. This study investigates the metabolic changes underlying pain progression and resolution, uncovering a novel compensatory mechanism in sensory neurons. Using the hyperalgesic priming model in male mice, we demonstrate that nerve growth factor (NGF) initially disrupted mitochondrial pyruvate oxidation, leading to acute allodynia. Surprisingly, this metabolic disruption persisted even after the apparent resolution of allodynia. We discovered that during the resolution phase, sensory neurons exhibit increased glutamine oxidation and upregulation of the major glutamine transporter ASCT2 in dorsal root ganglia (DRGs). This compensatory response plays a crucial role in pain resolution, as demonstrated by our experiments. Knockdown of ASCT2 prevents the resolution of NGF-induced allodynia and precipitates the transition to a chronic state. Furthermore, we show that the glutamine catabolite α-ketoglutarate attenuated glycolytic flux and alleviated allodynia in both acute and chronic phases of the hyperalgesic priming model. The importance of ASCT2 is further confirmed in a translational model, where its knockdown prevented the resolution of allodynia following plantar incision. These findings highlight the pivotal role of metabolic changes in pain resolution and identify ASCT2-mediated glutamine metabolism as a potential therapeutic target for chronic pain. Understanding these endogenous mechanisms that promote pain resolution can guide the development of novel interventions to prevent the transition pain from acute to chronic.Significance Statement Chronic pain is a widespread health issue with limited effective treatments. This study unveils a critical metabolic mechanism in sensory neurons that determines whether acute pain resolves or becomes chronic. We discovered that pain resolution depends on a compensatory increase in glutamine metabolism, mediated by the transporter ASCT2, rather than normalization of initial metabolic disruptions. This finding significantly advances our understanding of pain chronification and identifies a novel therapeutic target. By elucidating how the body naturally resolves pain, we open new avenues for developing treatments that could prevent acute pain from transitioning to chronic pain or treat existing chronic pain. This research has the potential to transform pain management strategies and improve quality of life for millions of pain sufferers.

Micro- and Macrostructural Language Features in Vertebrobasilar or Carotid System Stroke Without Diagnosis of Aphasia.

This study aimed to investigate the macro- and microstructural features of language in patients with ischemic stroke without aphasia. Participants were grouped according to arterial system damage and given the Aphasia Language Assessment Test (ADD) to detect aphasia. A narrative sample was obtained and analyzed for macrostructural and microstructural features of the language. The study sample consisted of 31 participants with ischemic stroke (15 vertebrobasilar system [VBS] involvement and 16 carotid system [CS] involvement) and 31 healthy participants, totaling 62 individuals. The healthy control group scored higher than the stroke group on the microstructural feature type-token ratio and mean length of utterance in the narrative analysis and on the auditory comprehension, repetition, naming, grammar, speech act, and writing subtests in ADD. Effort behavior, errors, edits, repetitions, and pauses among microstructural features and uncertainty, filler expression, and anomia among macrostructural features were significantly higher in the vertebrobasilar and CS groups than in the healthy control group. The total ADD score and speech fluency and reading subtest scores were significantly higher in individuals with VBS damage than in individuals with CS lesions (p < .05). Language components may be impaired differently in patients with carotid and vertebrobasilar lesions. Speech and language disorders in individuals who have experienced cerebrovascular accidents should be evaluated in the subacute and chronic phases, and the therapeutic needs of patients with ischemic stroke should be determined, regardless of the presence of a clinical aphasia diagnosis.

Fractional CO2 laser for the treatment of Peyronie's disease: A pilot clinical trial.

Introduction: Fractional CO2 laser therapy is used to treat fibrosing conditions similar to Peyronie’s disease (PD). The aim of the study was to evaluate the safety and efficacy of using a fractional CO2 laser in the management of chronic phase PD. Methods: This was a single-site, non-randomized, open-label study using a fractional CO2 laser. Subjects underwent three treatment sessions every six weeks with a fractional CO2 device. Topical triamcinolone was applied immediately after each treatment. Between treatments, patients performed penile modeling three times daily. Penile curvature assessments, self-reported questionnaires, and adverse event screenings were completed at baseline, 24 weeks, and at 52 weeks. Results: Five patients were included in the study. The median baseline penile curvature was 37.0° (interquartile range [IQR] 33.0°, 53.0°), and at 52 weeks, this had reduced to a median curvature to 28.0° (IQR 17.50°, 44.0°, p=0.03), representing a median reduction in penile curvature by 24.3% (IQR 17.0%, 47.5%). The International Index of Erectile Function Overall scores were comparable at baseline and at 52 weeks (median: 59.0, IQR: 42.5, 66.5 vs. median: 60.0, IQR 53.5, 70.0 respectively, p=0.81). Patients did report significant improvement in overall Peyronies’ disease questionnaire (PDQ) scores from baseline to 52 weeks after laser treatment (median 26.0, IQR15.0, 29.5, vs. median: 14.0, IQR 7.0, 22.50, respectively, p=0.03). Four patients reported self-limiting side effects immediately after laser therapy that resolved spontaneously within two weeks. Conclusions: Fractional CO2 laser therapy may serve as a well-tolerated and minimally invasive therapy for PD in the future, with results at 52 weeks being encouraging.

Strategic nucleic acid detection approaches for diagnosing African swine fever (ASF): navigating disease dynamics.

African swine fever (ASF) is a devastating disease caused by African swine fever virus (ASFV) and leads to significant economic losses in the pig farming industry. Given the absence of an effective vaccine or treatment, the mortality rate of ASF is alarmingly close to 100%. Consequently, the ability to rapidly and accurately detect ASFV on site and promptly identify infected pigs is critical for controlling the spread of this pandemic. The dynamics of the ASF virus load and antibody response necessitate the adoption of various detection strategies at different stages of infection, a topic that has received limited attention to date. This review offers detailed guidance for choosing appropriate ASF diagnostic techniques tailored to the clinical manifestations observed from the acute to chronic phases, including asymptomatic cases. We comprehensively summarize and evaluate the latest advancements in ASFV detection methods, such as CRISPR-based diagnostics, biosensors, and microfluidics. Additionally, we address the challenges of false negatives or positives due to ASF variants or the use of injected live attenuated vaccines. This review provides an exhaustive list of diagnostic tests suitable for detecting each stage of symptoms and potential target genes for developing new detection methods. In conclusion, we highlight the current challenges and future directions in ASFV detection, underscoring the need for continued research and innovation in this field.

The utility of Insulin Like Growth Factor Binding Proteins (IGFBPs-1, 2, 3) with genes expression in resistance to Imatinib and Nilotinib in chronic myeloid leukemia: a pilot study from Delta Egypt

Introduction: Resistance to tyrosine kinase inhibitors (TKIs) is an obstacle facing CML patients in spite of the high cure rate. In this context, a study association between IGFBP (1, 2, 3) genes expression and their proteins in CML with the response to TKI has been implicated. Patients and methods: 115 newly diagnosed CML in chronic phase (CP) followed up over 12 months under TKI. 116 apparently healthy individuals were used as a control. RT-qPCR amplification was used for detecting IGFBPs genes expression, and ELISA technique was used for measuring serum IGFBPs. Results: IGFBP-1 and IGFBP-3 genes expression, as well as their serum levels, were significantly higher in CML patients, whereas IGFBP-2 gene expression was not. Interestingly, IGFBP-1 gene expression and IGFBP-1 serum levels were significantly higher in resistant patients compared to responder patients. However, the expression of IGFBP-2, 3 genes and their serum were insignificant. Conclusion: IGFBP-1 gene expression and its serum were significantly correlated with resistance. It is currently recommended that IGF-receptor inhibitors be developed and utilized. We are hoping to optimize the cure rate for CML treated with TKIs. Keywords: IGFBP-1-3; Gene expression; CML; Imatinib; Nilotinib.

Profiling hippocampal expression of long non-coding RNA GM12371 in a rat model of vascular dementia

BackgroundDementia, characterized by synaptic dysfunction and memory loss, presents a significant challenge in medical research. Long non-coding RNAs (lncRNAs), known for their crucial roles in regulating gene expression, represent a gap in knowledge regarding their specific involvement in synaptic structure, transmission, and plasticity. This study aims to investigate the dynamic changes in hippocampal lncRNA GM12371 expression in response to acute and chronic hypoperfusion in the rat brain using the 2VO model.MethodsThe 2VO model was induced by permanently occluding the common carotid arteries. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate hippocampal lncRNA GM12371 expression at both acute (day 4) and chronic (day 28) stages post-2VO surgery. Comparative analysis was conducted with a sham-operated group.ResultsA notable reduction in GM12371 expression was observed in the rat hippocampus on day 4 following 2VO surgery compared to the sham group (P < 0.05). However, there was no significant difference in GM12371 expression between the sham and 2VO-28 groups.ConclusionThese findings suggest that the downregulation of GM12371 is a response to acute hippocampal blood flow reduction but tends to normalize during the chronic phase of cerebral hypoperfusion. This dynamic regulation of GM12371 expression may be significant in the adaptive response to vascular dementia. Further clinical studies are warranted to investigate potential peripheral alterations in GM12371 expression in individuals with dementia.

PET imaging identifies anti-inflammatory effects of fluoxetine and a correlation of glucose metabolism during epileptogenesis with chronic seizure frequency

The serotonergic system has shown to be altered during epileptogenesis and in chronic epilepsy, making selective serotonin reuptake inhibitors interesting candidates for antiepileptogenic therapy. In this study, we aimed to evaluate disease-modifying effects of fluoxetine during experimental epileptogenesis.Status epilepticus (SE) was induced by lithium-pilocarpine, and female rats were treated either with vehicle or fluoxetine over 15 days. Animals were subjected to 18F-FDG (7 days post-SE), 18F-GE180 (15 days post-SE) and 18F-flumazenil positron emission tomography (PET, 21 days post-SE). Uptake (18F-FDG), volume of distribution (18F-GE180) and binding potential (18F-flumazenil) were calculated. In addition, hyperexcitability testing and video-EEG monitoring were performed.Fluoxetine treatment did not alter brain glucose metabolism. 18F-GE180 PET indicated lower neuroinflammation in the hippocampus of treated animals (−22.6%, p = 0.042), but no differences were found in GABAA receptor density. Video-EEG monitoring did not reveal a treatment effect on seizure frequency. However, independently of the treatment, hippocampal FDG uptake 7 days after SE correlated with seizure frequency during the chronic phase (r = −0.58; p = 0.015).Fluoxetine treatment exerted anti-inflammatory effects in rats during epileptogenesis. However, this effect did not alter disease outcome. Importantly, FDG-PET in early epileptogenesis showed biomarker potential as higher glucose metabolism correlated to lower seizure frequency in the chronic phase.

Pharmaceutical Care in Patients with Side Effects to Oral Antineoplastic Agents: A Case Report

Background Chronic myeloid leukaemia (CML) is a haematopoietic stem cell disease characterised by the proliferation of granulocytes and their immature myeloid precursors. The treatments recommended are oral treatments dispensed in the outpatient unit (OU) of the hospital’s pharmacy service (PS), where patient-centred pharmaceutical care (PC) is essential to enhance therapeutic adherence, detect drug interactions and create a pharmacist-patient relationship to educate the patient on the main potential toxicities derived from the treatment and warning signs or symptoms requiring immediate attention. Methods We present the case of a 55-year-old woman, followed up in consultation by the Haematology Service (HS) since October 2021 for CML in the chronic phase. Results She started treatment on nilotinib 300 mg every 12 hours. The patient attended OU and was offered PC. After 12 months, nilotinib was well tolerated, but our patient experienced a loss of effectiveness, so HS decided to switch to dasatinib 100 mg daily. After one year of treatment, our patient was presented with symptoms of swelling and dyspnoea on moderate exertion. In January 2024, following a joint Haematology-Pharmacy session, a switch to bosutinib 400 mg daily was decided. After 15 days of treatment, the patient presented without an appointment due to a pruritic generalised rash on the torso, face, and extremities, being diagnosed with leukocytoclastic vasculitis. Conclusion In conclusion, we describe case reports of a patient who has a lack of effectiveness and ARs in several TKIs and the importance of identifying side effects, through early and close PC, in order for the patient’s evolution to be favourable.

Anti-inflammatory and remyelinating effects of fexagratinib in experimental multiple sclerosis.

FGF, VEGFR-2 and CSF1R signalling pathways play a key role in the pathogenesis of multiple sclerosis (MS). Selective inhibition of FGFR by infigratinib in MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) prevented severe first clinical episodes by 40%; inflammation and neurodegeneration were reduced, and remyelination was enhanced. Multi-kinase inhibition of FGFR1-3, CSFR and VEGFR-2 by fexagratinib (formerly known as AZD4547) may be more efficient in reducing inflammation, neurodegeneration and regeneration in the disease model. Female C57BL/6J mice were treated with fexagratinib (6.25 or 12.5 mg·kg-1) orally or placebo over 10 days either from time of EAE induction (prevention experiment) or onset of symptoms (suppression experiment). Effects on inflammation, neurodegeneration and remyelination were assessed at the peak of the disease (Day 18/20 post immunization) and the chronic phase of EAE (Day 41/42). In the prevention experiment, treatment with 6.25 or 12.5 mg·kg-1 fexagratinib prevented severe first clinical episodes by 66.7% or 84.6% respectively. Mice treated with 12.5 mg·kg-1 fexagratinib hardly showed any symptoms in the chronic phase of EAE. In the suppression experiment, fexagratinib resulted in a long-lasting reduction of severe symptoms by 91 or 100%. Inflammation and demyelination were reduced, and axonal density, numbers of oligodendrocytes and their precursor cells, and remyelinated axons were increased by both experimental approaches. Multi-kinase inhibition by fexagratinib in a well-tolerated dose of 1 mg·kg-1 in humans may be a promising approach to reduce inflammation and neurodegeneration, to slow down disease progression and support remyelination in patients.

Large expansion of plasma commensal viruses is associated with SIV pathogenesis in Macaca leonina.

Human immunodeficiency virus-1 (HIV-1) infection disrupts the homeostatic equilibrium between the host and commensal microbes. However, the dynamic changes of plasma commensal viruses and their role in HIV/simian immunodeficiency virus (SIV) pathogenesis are rarely reported. Here, we investigated the longitudinal changes of plasma virome, inflammation levels, and disease markers using an SIV-infected Macaca leonina model. Large expansions of plasma Anelloviridae, Parvoviridae, Circoviridae and other commensal viruses, and elevated levels of inflammation and D-dimer were observed since the chronic phase of SIV infection. Anelloviridae abundance appears to correlate positively with the CD4+ T cell count but negatively with SIV load especially at the acute phase, whereas other commensal viruses' abundances show opposite correlations with the two disease markers. Antiretroviral therapy slightly reduces but does not substantially reverse the expansion of commensal viruses. Furthermore, 1387 primate anellovirus open reading frame 1 sequences of more than 1500 nucleotides were annotated. The data reveal different roles of commensal viruses in SIV pathogenesis.