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Journal of Scleroderma and Related... Jun 2024Systemic sclerosis is a rare disease with a high mortality rate. It is a multisystem connective tissue disease due to endothelial autoimmune activation along with tissue...
Systemic sclerosis is a rare disease with a high mortality rate. It is a multisystem connective tissue disease due to endothelial autoimmune activation along with tissue and vascular fibrosis, inducing vasculopathy, with an angiogenesis wasting. The endothelial damage provokes platelet activation and immune cell adhesion. The detachment of endothelial cells leads to the interaction of platelets and collagen present in the exposed subendothelial layer. This provokes the activation of several coagulative factors, inducing a pro-thrombotic condition by thrombin generation, which converts fibrinogen into fibrin. Moreover, thrombin has other functions, such as the induction of hyperplasia in smooth muscle cells and fibroblasts, thereby favouring fibrosis. An increased risk of venous thromboembolism has been found in systemic sclerosis, whereas pulmonary hypertension may be due to the obstruction of small pulmonary arteries. Pulmonary veno-occlusive disease may also occur. Warfarin showed inconsistent results, while the outcomes of a randomised, placebo-controlled clinical trial on apixaban versus placebo are still awaited. A new anticoagulation strategy based on anti-factor XI drugs is being developed, with the aim of achieving optimal anticoagulation along with a low risk of bleeding. The molecule types under investigation in this category include monoclonal antibodies, small molecules, natural inhibitors, antisense oligonucleotides, and aptamers. Patients with systemic sclerosis may be ideal candidates for clinical trials planned to analyse the efficacy and safety of these molecules.
PubMed: 38910594
DOI: 10.1177/23971983241256250 -
Yonsei Medical Journal Jul 2024Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and... (Comparative Study)
Comparative Study
PURPOSE
Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib.
MATERIALS AND METHODS
We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias.
RESULTS
Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, =0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, =0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank =0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank =0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all >0.05).
CONCLUSION
Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly.
Topics: Humans; Nivolumab; Carcinoma, Hepatocellular; Phenylurea Compounds; Pyridines; Sorafenib; Liver Neoplasms; Male; Female; Retrospective Studies; Middle Aged; Aged; Adult; Progression-Free Survival
PubMed: 38910299
DOI: 10.3349/ymj.2023.0263 -
International Ophthalmology Jun 2024In this study we investigated the efficacy of short-term intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) in treating traumatic submacular...
OBJECTIVE
In this study we investigated the efficacy of short-term intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) in treating traumatic submacular hemorrhage.
METHODS
A total of 115 patients were diagnosed with submacular hemorrhage between 2018 and 2022 at Shenzhen Eye Hospital. In a retrospective analysis, we examined 13 of these patients who presented with submacular hemorrhage and choroidal rupture due to ocular trauma. Eight patients were treated with intravitreal anti-VEGF injection and 5 with oral drugs. We systematically analyzed changes in their ocular conditions pre and post-treatment. The evaluations encompassed best-corrected visual acuity (BCVA), optical coherence tomography, fundus fluorescein angiography, and retinal imaging.
RESULTS
The 13 patients diagnosed with submacular hemorrhage comprised of 10 males and 3 female, with their age ranging between 27 and 64 years, with an average age of 38.1 years (standard deviation [SD]: 11.27). A statistically significant reduction in central foveal thickness (CFT) was observed following intravitreal injections of anti-VEGF drugs (P = 0.03). In control group, the CFT was reduced without statistical significance (P = 0.10). The BCVA of the patients in treatment group improved significantly from 1.15 (SD: 0.62. Range: 0.4-2) to 0.63 (SD: 0.59. Range: 0.1-1.6), indicating an average increase of 4.13 lines (SD: 3.36. Range: 0-9) as measured by the visual acuity test using an eye chart (P = 0.01). The difference between baseline visual acuity and final visual acuity was not statistically significant in control group (P = 0.51).
CONCLUSION
Short-term administration of anti-VEGF drugs exhibited significant efficacy in reducing submacular hemorrhage following ocular trauma and enhancing visual acuity.
Topics: Humans; Intravitreal Injections; Retrospective Studies; Male; Female; Middle Aged; Angiogenesis Inhibitors; Adult; Vascular Endothelial Growth Factor A; Visual Acuity; Retinal Hemorrhage; Tomography, Optical Coherence; Fluorescein Angiography; Eye Injuries; Treatment Outcome; Bevacizumab; Ranibizumab; Fundus Oculi; Follow-Up Studies
PubMed: 38909337
DOI: 10.1007/s10792-024-03168-9 -
Scientific Reports Jun 2024Angiogenesis is a key process for the proliferation and metastatic spread of cancer cells. Anti-angiogenic peptides (AAPs), with the capability of inhibiting...
Angiogenesis is a key process for the proliferation and metastatic spread of cancer cells. Anti-angiogenic peptides (AAPs), with the capability of inhibiting angiogenesis, are promising candidates in cancer treatment. We propose AAPL, a sequence-based predictor to identify AAPs with machine learning models of improved prediction accuracy. Each peptide sequence was transformed to a vector of 4335 numeric values according to 58 different feature types, followed by a heuristic algorithm for feature selection. Next, the hyperparameters of six machine learning models were optimized with respect to the feature subset. We considered two datasets, one with entire peptide sequences and the other with 15 amino acids from peptide N-termini. AAPL achieved Matthew's correlation coefficients of 0.671 and 0.756 for independent tests based on the two datasets, respectively, outperforming existing predictors by a range of 5.3% to 24.6%. Further analyses show that AAPL yields higher prediction accuracy for peptides with more hydrophobic residues, and fewer hydrophilic and charged residues. The source code of AAPL is available at https://github.com/yunzheng2002/Anti-angiogenic .
Topics: Machine Learning; Angiogenesis Inhibitors; Peptides; Algorithms; Amino Acid Sequence; Humans
PubMed: 38909149
DOI: 10.1038/s41598-024-65062-9 -
International Ophthalmology Jun 2024To identify risk factors influencing visual outcomes in patients with pathological myopia-associated choroidal neovascularization (PM-CNV) following intravitreal...
PURPOSE
To identify risk factors influencing visual outcomes in patients with pathological myopia-associated choroidal neovascularization (PM-CNV) following intravitreal injections of conbercept.
METHODS
A total of 86 eyes from 86 patients received intravitreal conbercept in a 1 + PRN regimen. After the initial injection, patients were followed for 12 months. They were categorized into two groups based on their 12-month visual acuity change: those who achieved greater than a one-line improvement in BCVA (improved group; n = 65) and those who experienced a one-line or lesser improvement or a decrease in BCVA (non-improved group; n = 21).
RESULTS
Over the 12-month period, the mean BCVA in the improved group significantly improved from 0.82 to 0.41 LogMAR. In the non-improved group, BCVA changed from 1.24 to 1.09 LogMAR. Similarly, the mean CRT decreased from 426.21 μm at baseline to 251.56 μm at 12 months in the improved group, and from 452.47 to 382.45 μm in the non-improved group. Multivariable logistic regression analyses revealed that older age (OR 1.287; 95% CI 1.019-1.625; P = 0.034), poorer baseline BCVA (OR 6.422; 95% CI 1.625-25.384; P = 0.008), the presence of subfoveal CNV (OR 4.817; 95% CI 1.242-18.681; P = 0.023), and organized interlacing patterns of CNV morphology (OR 5.593; 95% CI 1.397-22.392; P = 0.015) emerged as independent risk factors correlated with worsened visual prognosis following intravitreal conbercept injections.
CONCLUSIONS
Conbercept demonstrates significant efficacy and safety in treating PM-CNV. Key factors influencing visual recovery post-treatment include older age, poorer baseline BCVA, the presence of subfoveal CNV, and organized interlacing patterns of CNV morphology.
Topics: Humans; Choroidal Neovascularization; Intravitreal Injections; Male; Myopia, Degenerative; Female; Recombinant Fusion Proteins; Middle Aged; Visual Acuity; Prognosis; Tomography, Optical Coherence; Fluorescein Angiography; Retrospective Studies; Follow-Up Studies; Adult; Aged; Treatment Outcome; Angiogenesis Inhibitors; Fundus Oculi
PubMed: 38907787
DOI: 10.1007/s10792-024-03177-8 -
Cell Communication and Signaling : CCS Jun 2024Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating...
Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating mitochondrial transcription and oxidative phosphorylation. In our study, we examined the impact of POLRMT on angiogenesis and found that its silencing or knockout (KO) in human umbilical vein endothelial cells (HUVECs) and other endothelial cells resulted in robust anti-angiogenic effects, impeding cell proliferation, migration, and capillary tube formation. Depletion of POLRMT led to impaired mitochondrial function, characterized by mitochondrial depolarization, oxidative stress, lipid oxidation, DNA damage, and reduced ATP production, along with significant apoptosis activation. Conversely, overexpressing POLRMT promoted angiogenic activity in the endothelial cells. In vivo experiments demonstrated that endothelial knockdown of POLRMT, by intravitreous injection of endothelial specific POLRMT shRNA adeno-associated virus, inhibited retinal angiogenesis. In addition, inhibiting POLRMT with a first-in-class inhibitor IMT1 exerted significant anti-angiogenic impact in vitro and in vivo. Significantly elevated expression of POLRMT was observed in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. POLRMT endothelial knockdown inhibited pathological retinal angiogenesis and mitigated retinal ganglion cell (RGC) degeneration in DR mice. At last, POLRMT expression exhibited a substantial increase in the retinal proliferative membrane tissues of human DR patients. These findings collectively establish the indispensable role of POLRMT in angiogenesis, both in vitro and in vivo.
Topics: Humans; Animals; Human Umbilical Vein Endothelial Cells; Mice; Mitochondria; DNA-Directed RNA Polymerases; Diabetic Retinopathy; Mice, Inbred C57BL; Cell Proliferation; Neovascularization, Pathologic; Male; Neovascularization, Physiologic; Cell Movement; Apoptosis; Angiogenesis
PubMed: 38907279
DOI: 10.1186/s12964-024-01712-9 -
BMC Ophthalmology Jun 2024Retinopathy of prematurity (ROP) is a proliferative disorder of the developing retina. Intravitreal bevacizumab injection (IVB) is an emerging treatment for severe forms...
BACKGROUND
Retinopathy of prematurity (ROP) is a proliferative disorder of the developing retina. Intravitreal bevacizumab injection (IVB) is an emerging treatment for severe forms of ROP, which does not restrict the visual field in comparison to laser therapy. The present study aimed to determine and evaluate the risk factors for ROP recurrence following IVB injection.
MATERIALS AND METHODS
In this retrospective study, 98 eyes of 49 infants with ROP who had received IVB injections as the primary treatment for type 1 ROP are included.
RESULTS
Fifty-four eyes (55.1%) had aggressive retinopathy of prematurity (A-ROP), and forty-four (44.9%) had Stage III Plus ROP in Zone II. ROP recurred in 13 eyes (13.26%) of 8 infants. The mean period between IVB and the ROP recurrence was 8.08 (95% CI:5.32-10.83) weeks. The infants who had ROP recurrence had lower birth weight (P value = 0.002), lower postmenstrual age at IVB injection (P value = 0.001), lower IVB injection gap period from birth (P value = 0.044), higher oxygen therapy requirement rate after IVB injection (P value < 0.001, OR:19.0) and higher oxygen therapy duration (P value = 0.006). The ROP severity, gestational age at birth, and diet were not statistically different between the recurrence and complete regression groups. Out of 13 eyes treated with laser photocoagulation because of ROP relapse, macula dragging occurred in one eye, and all the cases met the complete regression.
CONCLUSION
Low birth weight and oxygen therapy are the most important risk factors for ROP relapse, which requires meticulous oxygen treatment guidelines for premature infants.
Topics: Humans; Retinopathy of Prematurity; Bevacizumab; Intravitreal Injections; Retrospective Studies; Angiogenesis Inhibitors; Female; Male; Recurrence; Infant, Newborn; Gestational Age; Vascular Endothelial Growth Factor A; Risk Factors; Infant; Follow-Up Studies; Infant, Premature
PubMed: 38907228
DOI: 10.1186/s12886-024-03528-0 -
Indian Journal of Ophthalmology Jul 2024
Comparative Study
Topics: Humans; Intravitreal Injections; Administration, Oral; Rifampin; Central Serous Chorioretinopathy; Vascular Endothelial Growth Factor A; Propranolol; Angiogenesis Inhibitors; Adrenergic beta-Antagonists
PubMed: 38905466
DOI: 10.4103/IJO.IJO_2774_23 -
Frontiers in Immunology 2024Psoriasis is an inflammatory disease with systemic manifestations that most commonly presents as itchy, erythematous, scaly plaques on extensor surfaces. Activation of...
Psoriasis is an inflammatory disease with systemic manifestations that most commonly presents as itchy, erythematous, scaly plaques on extensor surfaces. Activation of the IL-23/IL-17 pro-inflammatory signaling pathway is a hallmark of psoriasis and its inhibition is key to clinical management. Granzyme K (GzmK) is an immune cell-secreted serine protease elevated in inflammatory and proliferative skin conditions. In the present study, human psoriasis lesions exhibited elevated GzmK levels compared to non-lesional psoriasis and healthy control skin. In an established murine model of imiquimod (IMQ)-induced psoriasis, genetic loss of GzmK significantly reduced disease severity, as determined by delayed plaque formation, decreased erythema and desquamation, reduced epidermal thickness, and inflammatory infiltrate. Molecular characterization revealed that GzmK contributed to macrophage secretion of IL-23 as well as PAR-1-dependent keratinocyte proliferation. These findings demonstrate that GzmK enhances IL-23-driven inflammation as well as keratinocyte proliferation to exacerbate psoriasis severity.
Topics: Psoriasis; Animals; Keratinocytes; Humans; Mice; Cell Proliferation; Granzymes; Interleukin-23; Inflammation; Imiquimod; Disease Models, Animal; Mice, Knockout; Female; Male; Mice, Inbred C57BL
PubMed: 38903528
DOI: 10.3389/fimmu.2024.1398120 -
Frontiers in Immunology 2024Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other... (Review)
Review
Drug-induced immune thrombocytopenia is an adverse reaction marked by accelerated destruction of blood platelets. In cancer therapy, thrombocytopenia has many other causes including bone marrow suppression induced by chemotherapeutic agents, infection, and progression of cancer; drug-induced thrombocytopenia can easily be misdiagnosed or overlooked. Here, we present a case of an ovarian cancer patient with a history of mixed connective tissue disease who underwent surgery followed by treatment with paclitaxel, cisplatin, and bevacizumab. The patient developed acute isolated thrombocytopenia after the sixth cycle. Serum antiplatelet antibody testing revealed antibodies against glycoprotein IIb. After we analyzed the whole therapeutic process of this patient, drug-induced immune thrombocytopenia was assumed, and bevacizumab was conjectured as the most probable drug. Thrombocytopenia was ultimately successfully managed using recombinant human thrombopoietin, prednisone, and recombinant human interleukin-11. We provide a summary of existing literature on immune thrombocytopenia induced by bevacizumab and discuss related mechanisms and triggers for drug-induced immune thrombocytopenia. The present case underscores the potential of bevacizumab to induce immune-mediated thrombocytopenia, emphasizing the need for heightened vigilance towards autoimmune diseases or an autoimmune-activated state as plausible triggers for rare drug-induced immune thrombocytopenia in cancer therapy.
Topics: Female; Humans; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Mixed Connective Tissue Disease; Ovarian Neoplasms; Purpura, Thrombocytopenic, Idiopathic
PubMed: 38903494
DOI: 10.3389/fimmu.2024.1382964