Control Disease Progression Research Articles

Targeting CD5 chimeric antigen receptor-engineered natural killer cells against T-cell malignancies

BackgroundChimeric antigen receptor engineered T cells (CAR-T) have demonstrated promising clinical efficacy in B-cell malignancies, and the approach has been extended to T-cell malignancies. However, the use of allogeneic T cells in CAR therapy poses a challenge due to the risk of graft-versus-host disease. Recently, natural killer (NK) cells have exhibited “off‑the‑shelf” availability. The nanobody-based CAR structures have attracted much attention for their therapeutic potential owing to the advantages of nanobody, including small size, optimal stability, high affinity and manufacturing feasibility. CD5, a common surface marker of malignant T cells, has three scavenger receptor cysteine-rich domains (D1-D3) in the extracellular region. The present study aims to construct “off‑the‑shelf” CAR-NK cells targeting the membrane-proximal domain of CD5 derived from nanobody against T-cell malignancies.MethodsAnti-CD5-D3 nanobody was screened by phage display technology, followed by constructing fourth-generation CAR plasmids ectopically producing IL-15 to generate CD5 CAR-NK cells derived from peripheral blood. And the second-generation CD5 CAR-T cells based on nanobody were generated, referred to as 5D.b CAR-T and 12 C.b CAR-T. Furthermore, CAR-NK cells without IL-15 (IL-15△ CAR-NK) were generated to assess the impact on cytotoxicity of CAR-NK cells. Cytotoxic activity against CD5+ hematologic malignant cell lines and normal T cells was exerted in vitro and NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt mouse model transplanted with Jurkat-Luc cells was used to evaluate the antitumor efficacy of CD5 CAR-NK cells in vivo.ResultsTwo nanobodies (5D and 12 C) competed for binding to the epitope of CD5-D3. 12 C CAR-NK cells were superior to 5D CAR-NK cells in antitumor potential and 12 C.b CAR-T cells exhibited superior cytotoxic activity than 5D CAR-T cells ex vivo. So, 12 C was regarded as the optimal nanobody. 12 C CAR-NK cells and IL-15△ CAR-NK cells exhibited robust cytotoxicity against CD5+ malignant cell lines and controlled disease progression in xenograft mouse model. 12 C CAR-NK cells demonstrated greater antitumor activity compared to that of IL-15△ CAR-NK cells in vitro and in vivo.ConclusionsTaken together, the fourth-generation nanobody-derived anti-CD5 CAR-NK cells may be a promising therapeutic against T-cell malignancies.

Differentiation fate of a stem-like CD4 T cell controls immunity to cancer.

The T cell response to cancer controls disease progression and response to immunotherapy1-3. Despite extensive knowledge regarding CD8 T cells, how CD4 T cells contribute to this process is less well understood. Here we identified a population of PD1+TCF1+ CD4 T cells with stem-like properties that are capable of self-renewal and differentiation into canonical CD4 effector cells. Primarily residing in tumour-draining lymph nodes (TDLNs), these tumour-specific CD4 T cells are restricted by T regulatory (Treg) cells to a stem-like fate that predominantly generated induced Treg (iTreg) cells, limiting effector CD8 T cell responses to the tumour. By contrast, upon Treg depletion, stem-like CD4 T cells differentiated into T helper 1 (TH1) cells, and via IFNγ production induced robust effector differentiation from TCF1+ CD8 T cells in TDLNs, a state we defined as 'active'. Notably, enforcing TBET expression in transferred stem-like CD4 T cells was sufficient to overcome the established restricted T cell state. Despite the presence of Treg cells, endogenous stem-like CD4 T cells actively generated TH1 cells, which were required to restore TDLN effector CD8 T cell differentiation, enhance tumour control and rescue response to immunotherapy. In agreement, TH1 differentiation in patients with kidney cancer predicted successful immunotherapy responses and improved progression-free survival. Together, these findings identify a stem-like CD4 T cell population that through alternative differentiation fates controls the switch between restricted and active T cell states with implications for cancer immunotherapies.

The correlation between stigma and treatment adherence, quality of life in patients with rheumatoid arthritis: A mixed-methods study.

To investigate the current status of stigma in patients with rheumatoid arthritis (RA), and its correlation with treatment adherence and quality of life. The convenience sample of 266 patients diagnosed with RA was surveyed at the rheumatology and immunology outpatient department of a tertiary hospital in Jiangsu Province from May 2022 to September 2022. In addition to this, 20 RA patients were purposively sampled for semi-structured in-depth interviews, and the data were analysed using content analysis methods. The total stigma's score of the 266 participants was (47.8 ± 10.8), which indicates a moderate level of stigma. The mean scores for alienation, stereotype endorsement, perceived discrimination, and social withdrawal were (2.2 ± 0.7), (2.4 ± 0.7), (2.9 ± 0.6), and (2.2 ± 0.6) respectively. A comparison of the average family monthly income, family roles, duration, disease activity, duration of morning stiffness, visual analogue scale score, C-reactive protein, erythrocyte sedimentation rate, and total stigma score revealed significant differences (p < 0.05). The total treatment adherence score was negatively correlated with the total stigma's score and scores in each dimension (p < 0.05). Similarly, the total psychological health score and total physical health score were negatively correlated with the total stigma score and scores in each dimension (p < 0.05). The qualitative study identified six themes: self-denial, discrimination, lack of disease-related knowledge, high medical costs, increased life burden and resistance to stigma. Stigma affects RA patients' treatment adherence and quality of life negatively. Healthcare workers are advised to develop comprehensive intervention programs that address the current status of stigma, with the aim of controlling disease progression, reducing disability rates, and improving the quality of life for RA patients.

Retinal vascular abnormality of non-perfusion and neovascularization in a toddler with neurofibromatosis type 1.

This report describes the case of a 13-month-old boy diagnosed with neurofibromatosis type 1, who presented with retinal vascular abnormalities including extensive non-perfusion and neovascularization. We also discuss the observed changes following photocoagulation treatment. A 13-month-old boy presented to the Department of Ophthalmology at Peking University People's Hospital with a reduction in the width of the left palpebral fissure for the past 6 months. The boy exhibited more than six café-au-lait spots larger than 5 mm in diameter on his trunk and legs. Fundus examination of the left eye revealed significant neovascularization in the temporal periphery of the retina, with late leakage and non-perfusion also noted temporally in fluorescein angiography (FA). Magnetic resonance imaging of the brain and orbits showed an enlarged left sphenoid body, a widened left cavernous sinus, and a large plexiform neurofibroma. Laser treatment was performed on the left eye. Five months later, the neovascularization was controlled. Careful fundus examinations and systemic reviews, especially FA, are essential. Timely laser treatment is crucial for controlling disease progression and preventing retinal detachment.

Low-dose tolvaptan to control disease progression in Chinese patients with autosomal dominant polycystic kidney disease: a retrospective cohort study.

Tolvaptan has been shown to be effective in the treatment of autosomal dominant polycystic kidney disease (ADPKD). However, there is limited evidence regarding optimal dosing and its application within the Chinese population. In this study, we aimed to determine whether a lower tolvaptan dose could effectively control ADPKD in Chinese patients. This retrospective, single-center cohort study was conducted in a real-world setting and included all patients newly diagnosed with rapidly progressive ADPKD who initiated tolvaptan treatment and maintained it for at least 12 months. Data were collected at baseline and at 1, 2, 4, 8, and 12 months after treatment initiation. Patients began with morning/evening tolvaptan doses of 7.5 mg/7.5 mg, and the dose was subsequently adjusted based on effectiveness and tolerability. The patients were categorized by baseline estimated glomerular filtration rate (eGFR) and final daily tolvaptan dose. Changes in eGFR and other key physiological indicators after treatment were compared within each group. The study included 43 patients with ADPKD, of whom 20 were female, with a median age of 34.3 years (range, 16-85 years). At 12 months, eGFR improved by 5.48 mL/min/1.73 m2 [95% confidence interval (CI): 2.68-8.29] (P<0.001) compared to baseline. Significant improvements were observed in patients with baseline eGFR levels of 30-59, 60-89, and ≥90 mL/min/1.73 m2 (P=0.007, 0.045, and 0.02, respectively), as well as in medium and high dose groups (P=0.002 and 0.02, respectively). At 12 months, the annual height-adjusted total kidney volume (HtTKV) growth slope decreased by -0.17 %/year (95% CI: -0.33 to -0.01) (P=0.04). Significant decreases were observed in patients with an eGFR of 30-59 mL/min/1.73 m2 (P=0.008) and in the medium dose group (P=0.03). Thirst was reported in 22 (51.2%) patients, all of whom experienced mild symptoms. No liver-associated adverse events were noted. Tolvaptan is well tolerated at low initial doses in Chinese patients with ADPKD. Significant improvements in eGFR and reduced HtTKV growth were observed in the overall population and across various baseline eGFR and final dose groups.

Emapalumab as a therapeutic intervention for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: A case series.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is characterized by a severe cytokine storm, heightened inflammatory response, and immune-mediated damage to tissues and organs. Standard treatment protocols for hemophagocytic lymphohistiocytosis often fall short in effectively controlling EBV-HLH, leading to a need for novel therapeutic options. Emapalumab, a monoclonal antibody targeting interferon-gamma, has shown promise due to its targeted cytokine modulation capabilities and favorable safety profile. This study aimed to evaluate the efficacy and safety of emapalumab in pediatric patients with EBV-HLH. The case series involved 4 pediatric patients diagnosed with EBV-HLH who did not achieve disease control despite receiving comprehensive treatment. All 4 pediatric patients were diagnosed with EBV-HLH. Emapalumab was introduced as an adjunctive therapeutic intervention alongside the HLH-94 or L-DEP regimens for these patients. Among the 4 patients, 1 experienced severe multiorgan dysfunction and opted to discontinue therapy. The remaining 3 patients showed controlled disease progression with significant clinical improvements following emapalumab administration. These improvements included reduced levels of inflammatory markers, normalization of blood counts and liver function, and decreased Epstein-Barr virus viral load. The findings suggest that emapalumab may be an effective and safe treatment option for pediatric EBV-HLH. However, further research is necessary to confirm these outcomes, especially in critically ill patients.

Role of HLA-B*58:01-restricted CD8+ T cells in HIV-1 subtype AE infection

Abstract HLA-B*58:01 and HLA-B*57 are protective alleles against HIV-1 subtype B or C infection whereas these HLA alleles have not been reported as protective in HIV-1 subtype AE infection. Although HLA-B*58:01-restricted and HLA-B*57-restricted HIV-1-specific CD8+ T cells have been thoroughly analyzed in subtype B or C infection, they have only been partially analyzed in subtype AE infection. We identified six HLA-B*58:01-restricted subtype AE epitopes in Vietnamese individuals infected with subtype AE. HLA-B*58:01-restricted T-cell responses to Gag epitopes, which may control disease progression in HLA-B*58:01+ and HLA-B*57+ individuals infected with subtype B or C, were not protective in subtype AE infection. These findings suggest that the loss of HLA-B*58:01-restricted T cells specific for some Gag epitopes and/or their reduced ability may account for the lack of protective effects conferred by HLA-B*58:01 in subtype AE infection.

Red Blood Cell Membrane Spontaneously Coated Nanoprodrug Based on Phosphatidylserine for Antiatherosclerosis Applications.

Atherosclerosis (AS) is characterized by the accumulation of lipids within the walls of coronary arteries, leading to arterial narrowing and hardening. It serves as the primary etiology and pathological basis for cardiovascular diseases affecting the heart and brain. However, conventional pharmacotherapy is constrained by inadequate drug delivery and pronounced toxic side effects. Moreover, the inefficacy of nanomedicine delivery systems in controlling disease progression may be attributed to nonspecific clearance by the mononuclear phagocyte system. Thus, a biomimetic platform spontaneously enveloped by red blood cell membrane is exploited for anti-atherosclerosis applications, offering favorable biocompatibility. The CLIKKPF polypeptide is introduced to develop red blood cell membrane spontaneously encapsulated nanotherapeutics only through simple coincubation. Given the functional modifications, RBC@P-LVTNPs is beneficial to facilitate the target drug delivery to the atherosclerotic lesion, responding precisely to the pathological ROS accumulation, thereby accelerating the on-demand drug release. Both in vivo and in vitro results also confirm the significant therapeutic efficacy and favorable biocompatibility of the biomimetic nanomedicine delivery system, thus providing a promising candidate for nanotherapeutics against AS.

Key genes and regulatory networks for diabetic retinopathy based on hypoxia-related genes: a bioinformatics analysis.

To prevent neovascularization in diabetic retinopathy (DR) patients and partially control disease progression. Hypoxia-related differentially expressed genes (DEGs) were identified from the GSE60436 and GSE102485 datasets, followed by gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Potential candidate drugs were screened using the CMap database. Subsequently, a protein-protein interaction (PPI) network was constructed to identify hypoxia-related hub genes. A nomogram was generated using the rms R package, and the correlation of hub genes was analyzed using the Hmisc R package. The clinical significance of hub genes was validated by comparing their expression levels between disease and normal groups and constructing receiver operating characteristic curve (ROC) curves. Finally, a hypoxia-related miRNA-transcription factor (TF)-Hub gene network was constructed using the NetworkAnalyst online tool. Totally 48 hypoxia-related DEGs and screened 10 potential candidate drugs with interaction relationships to upregulated hypoxia-related genes were identified, such as ruxolitinib, meprylcaine, and deferiprone. In addition, 8 hub genes were also identified: glycogen phosphorylase muscle associated (PYGM), glyceraldehyde-3-phosphate dehydrogenase spermatogenic (GAPDHS), enolase 3 (ENO3), aldolase fructose-bisphosphate C (ALDOC), phosphoglucomutase 2 (PGM2), enolase 2 (ENO2), phosphoglycerate mutase 2 (PGAM2), and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). Based on hub gene predictions, the miRNA-TF-Hub gene network revealed complex interactions between 163 miRNAs, 77 TFs, and hub genes. The results of ROC showed that the except for GAPDHS, the area under curve (AUC) values of the other 7 hub genes were greater than 0.758, indicating their favorable diagnostic performance. PYGM, GAPDHS, ENO3, ALDOC, PGM2, ENO2, PGAM2, and PFKFB3 are hub genes in DR, and hypoxia-related hub genes exhibited favorable diagnostic performance.

Genetic background affects neutrophil activity and determines the severity of autoinflammatory osteomyelitis in mice.

The knowledge about the contribution of the innate immune system to health and disease is expanding. However, to obtain reliable results, it is critical to select appropriate mouse models for in vivo studies. Data on genetic and phenotypic changes associated with different mouse strains can assist in this task. Such data can also facilitate our understanding of how specific polymorphisms and genetic alterations affect gene function, phenotypes, and disease outcomes. Extensive information is available on genetic changes in all major mouse strains. However, comparatively little is known about their impact on immune response and in particular on innate immunity. Here, we analyzed a mouse model of chronic multifocal osteomyelitis (CMO), an autoinflammatory disease driven exclusively by the innate immune system, which is caused by an inactivating mutation in the Pstpip2 gene. We investigated how the genetic background of BALB/c, C57BL/6J, and C57BL/6NCrl strains alters the molecular mechanisms controlling disease progression. While all mice developed the disease, symptoms were significantly milder in BALB/c and partially also in C57BL/6J when compared to C57BL/6NCrl. Disease severity correlated with the number of infiltrating neutrophils and monocytes and with the production of chemokines attracting these cells to the site of inflammation. It also correlated with increased expression of genes associated with autoinflammation, rheumatoid arthritis, neutrophil activation, and degranulation, resulting in altered neutrophil activation in vivo. Together, our data demonstrate striking effects of genetic background on multiple parameters of neutrophil function and activity influencing the onset and course of the CMO disease.

Deep learning fusion framework for automated coronary artery disease detection using raw heart sound signals

One of the most common cardiovascular diseases is coronary artery disease (CAD). Thus, it is crucial for early CAD diagnosis to control disease progression. Computer-aided CAD detection often converts heart sounds into graphics for analysis. However, this method relies heavily on the subjective experience of experts. Therefore, in this study, we proposed a method for CAD detection using raw heart sound signals by constructing a fusion framework with two CAD detection models: a multidomain feature model and a medical multidomain feature fusion model. We collected heart sound signal datasets from 400 participants, extracting 206 multidomain features and 126 medical multidomain features. The designed framework fused the same one-dimensional deep learning features with different multidomain features for CAD detection. The experimental results showed that the multidomain feature model and the medical multidomain feature fusion model achieved areas under the curve (AUC) of 94.7 % and 92.7 %, respectively, demonstrating the effectiveness of the fusion framework in integrating one-dimensional and cross-domain heart sound features through deep learning algorithms, providing an effective solution for noninvasive CAD detection.

Brachytherapy in Brain Metastasis Treatment: A Scoping Review of Advances in Techniques and Clinical Outcomes.

Brain metastases pose a significant therapeutic challenge in the field of oncology, necessitating treatments that effectively control disease progression while preserving neurological and cognitive functions. Among various interventions, brachytherapy, which involves the direct placement of radioactive sources into or near tumors or into the resected cavity, can play an important role in treatment. Current literature describes brachytherapy's capacity to deliver targeted, high-dose radiation while minimizing damage to adjacent healthy tissues-a crucial consideration in the choice of treatment modality. Furthermore, advancements in implantation techniques as well as in the development of different isotopes have expanded its efficacy and safety profile. This review delineates the contemporary applications of brachytherapy in managing brain metastases, examining its advantages, constraints, and associated clinical outcomes, and provides a comprehensive understanding of advances in the use of brachytherapy for brain metastasis treatment, with implications for improved patient outcomes and enhanced quality of life.

A five-in-one novel MOF-modified injectable hydrogel with thermo-sensitive and adhesive properties for promoting alveolar bone repair in periodontitis: Antibacterial, hemostasis, immune reprogramming, pro-osteo-/angiogenesis and recruitment

Periodontitis is a chronic inflammatory disease caused by plaque that destroys the alveolar bone tissues, resulting in tooth loss. Poor eradication of pathogenic microorganisms, persistent malignant inflammation and impaired osteo-/angiogenesis are currently the primary challenges to control disease progression and rebuild damaged alveolar bone. However, existing treatments for periodontitis fail to comprehensively address these issues. Herein, an injectable composite hydrogel (SFD/CS/ZIF-8@QCT) encapsulating quercetin-modified zeolitic imidazolate framework-8 (ZIF-8@QCT) is developed. This hydrogel possesses thermo-sensitive and adhesive properties, which can provide excellent flowability and post-injection stability, resist oral fluid washout as well as achieve effective tissue adhesion. Inspirationally, it is observed that SFD/CS/ZIF-8@QCT exhibits a rapid localized hemostatic effect following implantation, and then by virtue of the sustained release of zinc ions and quercetin exerts excellent collective functions including antibacterial, immunomodulation, pro-osteo-/angiogenesis and pro-recruitment, ultimately facilitating excellent alveolar bone regeneration. Notably, our study also demonstrates that the inhibition of osteo-/angiogenesis of PDLSCs under the periodontitis is due to the strong inhibition of energy metabolism as well as the powerful activation of oxidative stress and autophagy, whereas the synergistic effects of quercetin and zinc ions released by SFD/CS/ZIF-8@QCT are effective in reversing these biological processes. Overall, our study presents innovative insights into the advancement of biomaterials to regenerate alveolar bone in periodontitis.

General characteristics of orbital metastasis in breast cancer: a narrative review of case reports.

Breast-cancer metastasis has seen an increased incidence in recent years, owing to advancements in surveillance, diagnostic imaging, histopathological assessment, and treatment modalities. Metastasis to various sites, including the bone, lung, liver, and brain, is common in cancer patients. Orbital metastasis (OM) from breast cancer can lead to a range of symptoms, such as pain, palpebral ptosis, diplopia, ocular pain, vision loss, and a recessed eyeball. To explore the topic of systemic malignancies metastasizing to the orbit, a search was conducted on the PubMed service using keywords such as "orbit," "orbital," "cancer," "malignancy," and "metastasis." This review article aims to summarize the findings from the identified literature. Overall, 103 patients with breast cancer from 77 articles were investigated. The patients' mean age ± standard deviation was 58.73 ± 11.86years. Types of breast pathology observed in the evaluated patients included lobular (32.1%), ductal pathology (35.9%), and unspecified (32%). The most common symptom was vision change 37.9% and diplopia 26.2%. Despite the rarity of OM in breast cancer, it is crucial to consider this condition due to its potential to exacerbate the functional status of the neoplastic disease. The primary treatment approach for orbital metastasis involves radiation therapy, often combined with systemic chemotherapy, hormone therapy or targeted therapy. These interventions aim to minimize symptoms and control disease progression. It is encouraging that advancements in medication, along with timely diagnosis and treatment, have the potential to improve outcomes for patients with orbital metastasis. However, further research is necessary to comprehensively evaluate all aspects of breast cancer metastasis to rare organs. A deeper understanding of the underlying mechanisms and identification of potential therapeutic targets could enhance treatment strategies and ultimately improve patient prognosis.

Risk factors of disease activity and renal damage in patients with systemic lupus erythematosus.

To evaluate the clinical features of patients with Systemic Lupus Erythematosus (SLE) and explore the risk factors of disease activity and renal damage. A retrospective study involving 194 patients were performed. Patients were divided into lupus nephritis (LN) group (63.40%) and non-LN group (36.60%), different disease activity group, and different renal function group according to the clinical data. Multivariate logistic regression analysis showed that albumin (ALB), uric acid (UC), total cholesterol (TC), and anti-dsDNA antibodies were the influencing factors of LN in patients with SLE (P < 0.05); ALB, UC, and complement 3(C3) were the influencing factors of lupus disease activity (P < 0.05); UC, C3, and hemoglobin (HB) were the influencing factors of abnormal renal function in SLE patients. The results of the ROC curve showed that ALB, UA, and TC had certain predictive value for combined LN in patients with SLE, and the predictive value of ALB was greater than that of TC (P < 0.05); ALB, UA, and C3 being predictors of the activity of patients with SLE; BUN, UA, and HB all had certain predictive value for the abnormal renal function in patients with LN. SLE patients have the high incidence of renal impairment. The results of this study suggest that patients with SLE should regularly monitor the levels of ALB, UA, TC, C3, and HB, as well as pay attention to the intervention of hyperlipidemia and hyperuricemia in patients with SLE to better control disease progression.

Reviewing the Structure-Function Paradigm in Polyglutamine Disorders: A Synergistic Perspective on Theoretical and Experimental Approaches.

Polyglutamine (polyQ) disorders are a group of neurodegenerative diseases characterized by the excessive expansion of CAG (cytosine, adenine, guanine) repeats within host proteins. The quest to unravel the complex diseases mechanism has led researchers to adopt both theoretical and experimental methods, each offering unique insights into the underlying pathogenesis. This review emphasizes the significance of combining multiple approaches in the study of polyQ disorders, focusing on the structure-function correlations and the relevance of polyQ-related protein dynamics in neurodegeneration. By integrating computational/theoretical predictions with experimental observations, one can establish robust structure-function correlations, aiding in the identification of key molecular targets for therapeutic interventions. PolyQ proteins' dynamics, influenced by their length and interactions with other molecular partners, play a pivotal role in the polyQ-related pathogenic cascade. Moreover, conformational dynamics of polyQ proteins can trigger aggregation, leading to toxic assembles that hinder proper cellular homeostasis. Understanding these intricacies offers new avenues for therapeutic strategies by fine-tuning polyQ kinetics, in order to prevent and control disease progression. Last but not least, this review highlights the importance of integrating multidisciplinary efforts to advancing research in this field, bringing us closer to the ultimate goal of finding effective treatments against polyQ disorders.

Bibliometric analysis and description of research trends in the treatment of psoriasis with biologic agents in the past two decades (2004–2023)

Background Biologics are essential in treating psoriasis. In recent years, the pathogenesis exploration and development of new target drugs have provided a more complete evidence-based foundation for the biological treatment of psoriasis. This study aims to use bibliometrics to analyze the research status and development trends of biologics in psoriasis. Methods The bibliometric analysis of publications related to biologics in psoriasis from 2004 to 2023 was conducted using the Web of Science Core Collection (WoSCC) database as the search data source. To perform the bibliometric analysis and create visual knowledge graphs, CiteSpace, the Bibliometrix R package, and VOSviewers were utilized. Results The study included a total of 3800 articles. The United States had the highest number of publications. The leading authors and institutions were Steven R. Feldman and the University of Manchester, respectively, in the global partnership. The cluster plot divided all keywords into 11 categories. Currently, Secukinumab and Guselkumab are representative biological agents being studied due to their considerable efficacy and long-term safety. Conclusions Targeted therapy has emerged as a significant trend in the current treatment of psoriasis. Early and active use of biologics can effectively control disease progression, prevent or delay the occurrence of comorbidities, and may even alter the natural course of psoriasis. However, further investigation is required to fully understand the specific mechanisms of psoriasis and the use of biological agents.

#2926 The impact of GLP-1 receptor agonists on metabolic control and diabetic kidney disease progression

Abstract Background and Aims Diabetic kidney disease is the leading cause of end-stage kidney disease in developed world. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are a class of drugs that have shown benefits beyond glycemic control, with a reduction in cardiovascular risk and renoprotective effects. The aim of this study was to assess the effect of GLP-1 RA in metabolic control and progression of CKD. Our objective was to analyze the impact and efficacy of GLP-1 RA in patients with chronic kidney disease (CKD). Method This was a retrospective cohort study, that included type 2 diabetic patients with CKD, followed in Nephrology outpatient clinic, who started treatment with GLP-1 RA between January 2019 and February 2022. Clinical, demographic and laboratory data were collect at the initiation of the therapy, 6 months and 1 year during follow-up. Results A total of 66 patients were included, of whom 63.6% (n = 42) males with a mean age of 67.8 ± 10.9 years. 95.5% (n = 63) had history of hypertension, 59.1% (n = 39) heart failure and 16.7% (n = 11) peripheral arterial disease. The median estimated glomerular filtration rate (eGFR) at beginning of the treatment was 45 [31.8-65] mL/min/1.73 m2, mean HbA1c of 9.1 ± 1.7%, and mean weight 89.4 ± 15.4 kg. The most frequently prescribed GLP-1 RA were liraglutide (34.8%, n = 23) and dulaglutide (34.8%, n = 23), followed by semaglutide (21.2%, n = 14) and exenatide (1.5%, n = 1). Regarding concomitant therapy, all of the patients were on renin-angiotensin-aldosterone system antagonists, 90.9% (n = 60) were on SGLT2 inhibitors, and 68.2% (n = 45) were on insulin. At 6 months follow-up, there was a statistically significant reduction in HbA1c (9.2 ± 1.8 VS 7.8 ± 1.7, p &amp;lt; 0.001) and weight (89.4 ± 15.4 VS 86.8 ± 15.7, p = 0.002). There were no significant differences in eGFR, lipidic profile and albuminuria. At 1 year follow-up, there was significant reduction of HbA1c (Z = −4.6, p &amp;lt; 0.001), weight (Z = −3.1, p = 0.002), and a statistically significant increase of eGFR (49.5 ± 25.4 VS 56.9 ± 27.0, p = 0.007), with no significant differences in lipidic profile and albuminuria. During the follow-up period, 5 patients voluntarily discontinued the treatment, and 1 patient suspended it due to gastrointestinal adverse effects. Conclusion Our study findings reinforce the existing evidence supporting the renoprotective effects of GLP-1 RA. We observed a notable improvement in metabolic control, as evidenced by significant reduction of HbA1c and weight, particularly at the 6th month. There were no significant differences in albuminuria during the follow up time, but an unexpected increase in eGFR.

Progress in lipoarabinomannan antigen detection for tuberculosis diagnosis in people living with HIV/AIDS

Tuberculosis (TB) is the leading cause of death among people living with HIV/AIDS (PLWHA), posing a significant disease burden. Early TB screening in PLWHA is a key intervention to reduce transmission and control disease progression. ​Lipoarabinomannan (LAM) is a glycolipid of Mycobacterium tuberculosis (MTB) that can be detected in the urine of tuberculosis patients. LAM is useful for the rapid and accurate diagnosis of tuberculosis. This article reviews LAM and its application and limitations in the diagnosis of PLWHA, hoping to provide a reference for the diagnosis of tuberculosis in PLWHA.

The fibrosis-4 index is a prognostic factor for cholangiocarcinoma patients who received immunotherapy.

Research of immunotherapy for cholangiocarcinoma has yielded some results, but more clinical data are needed to prove its efficacy and safety. Moreover, there is a need to identify accessible indexes for selecting patients who may benefit from such treatments. The medical records of 66 cholangiocarcinoma patients who underwent immunotherapy were retrospectively collected. The effectiveness of immunotherapy was assessed by tumor response, progression-free survival (PFS), and overall survival (OS), while safety was evaluated by adverse events during treatment. Univariate and multivariate Cox regression analyses were performed to identify prognostic risk factors for PFS and OS, and Kaplan-Meier curves of potential prognostic factors were drawn. Overall, in this study, immunotherapy achieved an objective response rate of 24.2% and a disease control rate of 89.4% for the included patients. The median PFS was 445 days, and the median OS was 772.5 days. Of the 66 patients, 65 experienced adverse events during treatment, but none had severe consequences. Multivariate Cox analysis indicated that tumor number is a prognostic risk factor for disease progression following immunotherapy in cholangiocarcinoma patients, while tumor differentiation and the fibrosis-4 (FIB-4) index are independent risk factors for OS. In general, immunotherapy for cholangiocarcinoma is safe, with adverse events remaining within manageable limits, and it can effectively control disease progression in most patients. The FIB-4 index may reflect the potential benefit of immunotherapy for patients with cholangiocarcinoma.