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1.
Gulf J Oncolog ; 1(45): 49-63, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38774933

RESUMO

INTRODUCTION: rhTSH-assisted radioiodine therapy of multinodular goiter is not fully known and only a few studies, with a limited number of patients have evaluated the effect of rhTSH assisted radioiodine therapy beyond 1 year. Though there is an effective and safe management of benign non-toxic MNG available, it is not applicable to all patient categories in Kuwait covering the impact of the past environmental events (Gulf War) and the genetic relation. The proposed project aims to address those points raised, that is exclusive to the Kuwait population. MATERIALS AND METHODS: In this cohort study, 2 groups of patients, group one (G1) and group two (G2) patients (N=50, ≥18 years old) went undergo evaluated according to a proposed criteria followed by FNA to exclude cancer, toxicity and those who have refused surgery. All patients had a CT scan, TSH, T3, T4 and CBC and complete biomedical tests at a 6-months interval during the treatment period and the follow up. The Volumetric application of GE 670 SPECT/CT (i.e. Xeleris) and in-house developed MATLAB used for quantitative measurement. All patients had a 131-I uptake at baseline and 24 intervals post intramuscular a single dose of 0.3mg or 0.1mg (group 1, group 2) of rhTSH. RESULTS: There was no significant difference in TSH levels at 24-month follow-up between the two groups (p=0.327), whereas there was a statistically significant difference at the baseline and at the 6-months interval between the 2 groups for T4. Post treatment follow up at the 24-hour time point, Group 1 displayed significantly higher uptake than Group 2 (G1:41.74 ± 6.27 vs. G2:34.80 ± 3.84, p < 0.001). The change in I131 uptake from baseline to 24 hours was significantly greater in Group 1compared to Group 2 (p < 0.001). The ROC analysis (AUC) post treatment indicated an excellent discriminatory power for AUC (0.960) and (p < 0.001). There was a much better correlation posttreatment between BMI and thyroid volume for group 1 (R2=0.661) than for group 2 (R2=0.008). Our results suggest 42.1% thyroid volume reduction for group 1 and 20% for group 2. CONCLUSION: The study underscores the potential benefits of the higher rhTSH dose (0.3mg) in managing multinodular non-toxic goiter for the Kuwaiti population and the region considering the impact of dietary, and experience to the drastic environmental exposure.


Assuntos
Bócio Nodular , Radioisótopos do Iodo , Humanos , Masculino , Kuweit , Radioisótopos do Iodo/uso terapêutico , Feminino , Bócio Nodular/radioterapia , Pessoa de Meia-Idade , Adulto , Tireotropina , Proteínas Recombinantes/uso terapêutico
3.
Medicine (Baltimore) ; 103(19): e38106, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728498

RESUMO

RATIONALE: Recombinant human endostatin (Endostar) is extensively utilized in China for the clinical management of patients with driver gene-negative non-small cell lung cancer (NSCLC) at stage TNM IV. This report describes the case of a lung cancer patient treated exclusively with Endostar maintenance therapy, who experienced a rapid deterioration in respiratory function. PATIENT CONCERNS: The case involved a patient with a pathologically confirmed squamous cell carcinoma of the left lung, treated in our department. Following 1 month of albumin-bound paclitaxel chemotherapy and localized radiotherapy for the left lung lesion, the patient initiated treatment with a single agent, Endostar 30mg, on October 19, 2021. The medication was administered via intravenous infusion over a 7 days. DIAGNOSIS: On October 23, 2021, the patient exhibited symptoms of chest constriction, discomfort, coughing, and sputum production. By October 28, the patient presented with pronounced dyspnea and respiratory distress. An emergency CT scan detected pericardial tamponade and significant deviations in several blood parameters from pretreatment values. INTERVENTIONS: Percardial puncture and catheter drainage were recommended as therapeutic intervention. OUTCOMES: Considering the patient advanced age, the patient and their family opted to refuse this medical procedure, leading to the patient unfortunate demise on November 2, 2021. LESSONS: Medical professionals should remain vigilant for the potential, albeit rare, risk of Endostar inducing acute pericardial tamponade, a severe and potentially fatal complication.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Tamponamento Cardíaco , Endostatinas , Neoplasias Pulmonares , Proteínas Recombinantes , Humanos , Carcinoma Pulmonar de Células não Pequenas/complicações , Endostatinas/uso terapêutico , Neoplasias Pulmonares/complicações , Masculino , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/terapia , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Evolução Fatal , Idoso , Pessoa de Meia-Idade , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico
4.
N Engl J Med ; 390(18): 1690-1698, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38718359

RESUMO

In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP.


Assuntos
Proteína ADAMTS13 , Púrpura Trombocitopênica Trombótica , Feminino , Humanos , Proteína ADAMTS13/imunologia , Proteína ADAMTS13/uso terapêutico , Complexo Antígeno-Anticorpo/sangue , Complexo Antígeno-Anticorpo/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/imunologia , Púrpura Trombocitopênica Trombótica/terapia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico , Adulto , Negro ou Afro-Americano , Troca Plasmática , Resultado do Tratamento
5.
Nat Commun ; 15(1): 4119, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750020

RESUMO

Sepsis results from systemic, dysregulated inflammatory responses to infection, culminating in multiple organ failure. Here, we demonstrate the utility of CD5L for treating experimental sepsis caused by cecal ligation and puncture (CLP). We show that CD5L's important features include its ability to enhance neutrophil recruitment and activation by increasing circulating levels of CXCL1, and to promote neutrophil phagocytosis. CD5L-deficient mice exhibit impaired neutrophil recruitment and compromised bacterial control, rendering them susceptible to attenuated CLP. CD5L-/- peritoneal cells from mice subjected to medium-grade CLP exhibit a heightened pro-inflammatory transcriptional profile, reflecting a loss of control of the immune response to the infection. Intravenous administration of recombinant CD5L (rCD5L) in immunocompetent C57BL/6 wild-type (WT) mice significantly ameliorates measures of disease in the setting of high-grade CLP-induced sepsis. Furthermore, rCD5L lowers endotoxin and damage-associated molecular pattern (DAMP) levels, and protects WT mice from LPS-induced endotoxic shock. These findings warrant the investigation of rCD5L as a possible treatment for sepsis in humans.


Assuntos
Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos , Sepse , Animais , Sepse/imunologia , Sepse/tratamento farmacológico , Camundongos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Fagocitose , Quimiocina CXCL1/metabolismo , Quimiocina CXCL1/genética , Modelos Animais de Doenças , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Ceco/cirurgia , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Humanos , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Ligadura , Lipopolissacarídeos , Choque Séptico/imunologia
6.
Orphanet J Rare Dis ; 19(1): 189, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715031

RESUMO

BACKGROUND: Mucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of ß-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII. METHODS: This disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (N ≈ 50 planned) treated with vestronidase alfa or any other management approach. Data are monitored and recorded in compliance with Good Clinical Practice guidelines and planned interim analyses of captured data are performed annually. Here we summarize the safety and efficacy outcomes as of 17 November 2022. RESULTS: As of the data cutoff date, 35 patients were enrolled: 28 in the Treated Group and seven in the Untreated Group. Mean (SD) age at MPS VII diagnosis was 4.5 (4.0) years (range, 0.0 to 12.4 years), and mean (SD) age at DMP enrollment was 13.9 (11.1) years (range, 1.5 to 50.2 years). Ten patients (29%) had a history of nonimmune hydrops fetalis. In the 23 patients who initiated treatment prior to DMP enrollment, substantial changes in mean excretion from initial baseline to DMP enrollment were observed for the three urinary glycosaminoglycans (uGAGs): dermatan sulfate (DS), -84%; chondroitin sulfate (CS), -55%; heparan sulfate (HS), -42%. Also in this group, mean reduction from initial baseline to months 6, 12, and 24 were maintained for uGAG DS (-84%, -87%, -89%, respectively), CS (-70%, -71%, -76%, respectively), and HS (+ 3%, -32%, and - 41%, respectively). All adverse events (AEs) were consistent with the known vestronidase alfa safety profile. No patients discontinued vestronidase alfa. One patient died. CONCLUSIONS: To date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing.


Assuntos
Terapia de Reposição de Enzimas , Glucuronidase , Mucopolissacaridose VII , Proteínas Recombinantes , Humanos , Mucopolissacaridose VII/tratamento farmacológico , Glucuronidase/uso terapêutico , Glucuronidase/metabolismo , Masculino , Pré-Escolar , Feminino , Criança , Terapia de Reposição de Enzimas/métodos , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Lactente , Estudos Longitudinais , Adolescente
7.
N Engl J Med ; 390(19): 1745-1755, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38749032

RESUMO

BACKGROUND: Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. METHODS: We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. RESULTS: A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P = 0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P = 0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. CONCLUSIONS: Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).


Assuntos
Hemorragia Cerebral , Inibidores do Fator Xa , Fator Xa , Hematoma , Proteínas Recombinantes , Humanos , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Idoso , Masculino , Feminino , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/induzido quimicamente , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Fator Xa/uso terapêutico , Fator Xa/efeitos adversos , Hematoma/induzido quimicamente , Hematoma/tratamento farmacológico , Idoso de 80 Anos ou mais , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Doença Aguda
8.
Drug Des Devel Ther ; 18: 1083-1101, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585254

RESUMO

The clinical use of agalsidase alfa as enzyme replacement therapy (ERT) for Fabry disease (FD) has spread since 2001, and a large body of evidence of its effectiveness has been collected. This review presents the clinical and laboratory results achieved with agalsidase alfa, which has been published in the literature. Agalsidase alfa infusion slows down or stops the progression of renal damage, expressed by reduction or stabilization of the annual decline of the glomerular filtration rate; yearly decrease of glomerular filtration rate (slope) sometimes is reduced until its stabilization. ERT prevents or reduces the occurrence of hypertrophic cardiomyopathy or slows the increase over time if it is already present. Moreover, regarding neurological manifestations, ERT improves neuropathic pain and quality of life, and recent data indicated that it may also prevent the burden of cerebrovascular disease. In addition to ERT's clinical benefits, crucial topics like the most appropriate time to start therapy and the role of anti-drug antibodies (ADA) are analyzed. Treatment with agalsidase alfa in patients with FD substantially improves their outcomes and enhances their quality of life in patients with FD.


Assuntos
Doença de Fabry , Isoenzimas , Humanos , Doença de Fabry/tratamento farmacológico , Terapia de Reposição de Enzimas/métodos , Qualidade de Vida , Resultado do Tratamento , alfa-Galactosidase/uso terapêutico , Anticorpos , Proteínas Recombinantes/uso terapêutico
9.
J Paediatr Child Health ; 60(2-3): 53-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572627

RESUMO

AIM: Hormone replacement therapy with testosterone for pubertal induction in boys with congenital hypogonadotropic hypogonadism (CHH) achieves virilization but not spermatogenesis. By contrast, human chorionic gonadotropin (hCG) and recombinant follicle stimulating hormone (rFSH) provides both virilization and spermatogenesis. Fertility outcomes of boys treated with recombinant therapy during adolescence have been infrequently described. We report fertility induction and pregnancy outcomes in CHH patients treated with recombinant gonadotropins during puberty. METHODS: Data of six subjects with CHH (n = 3 Kallmann syndrome & n = 3 Isolated hypogonadotropic hypogonadism) treated with hCG and FSH for pubertal induction were reviewed. Of these, five underwent subsequent fertility induction while one desired fertility at the end of pubertal induction. RESULTS: Partners of all subjects achieved pregnancies using hCG and rFSH, all with full term live births. All infants were clinically normal. CONCLUSION: This study provides early evidence of proof of concept of use of gonadotropin induction of puberty being beneficial in subsequent fertility outcome.


Assuntos
Gonadotropina Coriônica , Hipogonadismo , Adulto , Gravidez , Lactente , Feminino , Adolescente , Humanos , Masculino , Gonadotropina Coriônica/uso terapêutico , Hipogonadismo/tratamento farmacológico , Hormônio Foliculoestimulante , Testosterona/uso terapêutico , Fertilidade , Proteínas Recombinantes/uso terapêutico , Puberdade , Virilismo
10.
Int Wound J ; 21(4): e14851, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38563121

RESUMO

Scarring following oral and maxillofacial trauma can have significant aesthetic and functional repercussions. Recombinant human epidermal growth factor (rhEGF) has emerged as a potential therapeutic agent to enhance wound healing and minimise scar formation. This retrospective study analysed data from March 2020 to June 2023 at a single institution. A total of 105 patients were divided into a control group (n = 70) receiving standard treatment and an observation group (n = 35) receiving standard treatment plus rhEGF. The primary outcomes were the incidence of scar hyperplasia and infection rates, with the secondary outcome being scar aesthetics measured by the visual analogue scale (VAS). No significant differences were found in baseline characteristics between the two groups. The observation group showed a significant reduction in scar hyperplasia (14.3% vs. 57.1%, χ2 = 20.98, p < 0.01) and infection rates (5.7% vs. 21.4%, χ2 = 4.246, p < 0.05) compared to the control group. VAS scores indicated a superior aesthetic outcome in the observation group at all post-treatment timepoints (p < 0.01). rhEGF treatment in oral and maxillofacial trauma patients resulted in favourable healing outcomes and reduced scar formation, improving aesthetic results. These findings highlight the therapeutic potential of rhEGF and underscore the need for larger-scale trials to further investigate its benefits.


Assuntos
Cicatriz , Traumatismos Maxilofaciais , Humanos , Cicatriz/tratamento farmacológico , Hiperplasia/tratamento farmacológico , Estudos Retrospectivos , Proteínas Recombinantes/uso terapêutico , Fator de Crescimento Epidérmico/uso terapêutico , Cicatrização , Traumatismos Maxilofaciais/tratamento farmacológico
11.
J Stroke Cerebrovasc Dis ; 33(6): 107310, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636321

RESUMO

OBJECTIVES: Heparin-induced thrombocytopenia is a known complication of heparin exposure with potentially life-threatening sequelae. Direct thrombin inhibitors can be substituted for heparin in patients with heparin-induced thrombocytopenia that require anticoagulation. However, the use of direct thrombin inhibitors as a substitute for heparin has not been widely reported in the neuroendovascular literature. MATERIALS AND METHODS: Here we report the first use of the direct thrombin inhibitor bivalirudin in a neuroendovascular procedure as a substitute for heparin in a patient with a ruptured pseudoaneurysm and heparin-induced thrombocytopenia, and review the literature on the use of bivalirudin and argatroban for such patients. RESULTS: Bivalirudin was safely and effectively used in the case reported, with no thrombotic or hemorrhagic complications. Our literature review revealed a paucity of studies on the use of heparin alternatives, including bivalirudin, in neuroendovascular procedures in patients with heparin-induced thrombocytopenia. CONCLUSIONS: Heparin-induced thrombocytopenia is an important iatrogenic disease process in patients undergoing neuroendovascular procedures, and developing protocols to diagnose and manage heparin-induced thrombocytopenia is important for healthcare systems. While further research needs to be done to establish the full range of anticoagulation options to substitute for heparin, our case indicates bivalirudin as a potential candidate.


Assuntos
Anticoagulantes , Antitrombinas , Heparina , Hirudinas , Fragmentos de Peptídeos , Proteínas Recombinantes , Trombocitopenia , Humanos , Masculino , Pessoa de Meia-Idade , Falso Aneurisma/cirurgia , Falso Aneurisma/tratamento farmacológico , Aneurisma Roto/cirurgia , Aneurisma Roto/diagnóstico por imagem , Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Antitrombinas/uso terapêutico , Substituição de Medicamentos , Procedimentos Endovasculares/efeitos adversos , Heparina/efeitos adversos , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/tratamento farmacológico , Fragmentos de Peptídeos/uso terapêutico , Fragmentos de Peptídeos/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombocitopenia/tratamento farmacológico , Resultado do Tratamento
13.
ACS Appl Mater Interfaces ; 16(17): 21438-21449, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38626407

RESUMO

Thrombolytic therapy is one of the most effective treatments for thrombus dissolution and recanalization of blocked vessels in thrombotic diseases. However, the application of the thrombolytic strategy has been limited due to unsatisfactory thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications. Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology, which exhibits a better thrombolytic efficacy than urokinase and recombinant streptokinase. Inspired by the natural affinity of platelets in hemostasis and pathological thrombosis, we developed a platelet membrane (PM)-coated r-SAK (PM-r-SAK). Results from animal experiments and human in vitro studies showed that the PM-r-SAK had a thrombolytic efficacy equal to or better than its 4-fold dose of r-SAK. In a totally occluded rabbit femoral artery thrombosis model, the PM-r-SAK significantly shortened the initial recanalization time compared to the same dose and 4-fold dose of r-SAK. Regarding the recanalized vessels, the PM-r-SAK prolonged the time of reperfusion compared to the same dose and 4-fold dose of r-SAK, though the differences were not significant. An in vitro thrombolytic experiment demonstrated that the thrombolytic efficacy of PM-r-SAK could be inhibited by platelet-poor plasma from patients taking aspirin and ticagrelor. PM coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the PM-r-SAK and can be inhibited by aspirin- and ticagrelor-treated plasma.


Assuntos
Plaquetas , Fibrinolíticos , Metaloendopeptidases , Trombose , Animais , Coelhos , Humanos , Trombose/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Fibrinolíticos/química , Fibrinolíticos/uso terapêutico , Fibrinolíticos/farmacologia , Metaloendopeptidases/metabolismo , Terapia Trombolítica , Proteínas Recombinantes/uso terapêutico , Masculino , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos
14.
Am J Cardiovasc Drugs ; 24(3): 385-398, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38683263

RESUMO

AIM: The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI. METHODS: Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72-0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57-0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66-0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72-0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13-2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24-0.65; P = 0.0003). CONCLUSION: Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI.


Assuntos
Antitrombinas , Heparina , Hirudinas , Fragmentos de Peptídeos , Intervenção Coronária Percutânea , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Proteínas Recombinantes , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Hirudinas/efeitos adversos , Hirudinas/administração & dosagem , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Fragmentos de Peptídeos/uso terapêutico , Fragmentos de Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Heparina/efeitos adversos , Heparina/uso terapêutico , Heparina/administração & dosagem , Antitrombinas/uso terapêutico , Antitrombinas/efeitos adversos , Hemorragia/induzido quimicamente , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
ACS Biomater Sci Eng ; 10(5): 3188-3202, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38592024

RESUMO

Chronic wound repair is a clinical treatment challenge. The development of multifunctional hydrogels is of great significance in the key aspects of treating chronic wounds, including reducing oxidative stress, promoting angiogenesis, and improving the natural remodeling of extracellular matrix and immune regulation. In this study, we prepared a composite hydrogel, sodium alginate (SA)@MnO2/recombinant humanized collagen III (RHC)/mesenchymal stem cells (MSCs), composed of SA, MnO2 nanoparticles, RHC, and MSCs. The hydrogel has high mechanical properties and good biocompatibility. In vitro, SA@MnO2/RHC/MSCs hydrogel effectively enhanced the formation of intricate tubular structures and angiogenesis and showed synergistic effects on cell proliferation and migration. In vivo, the SA@MnO2/RHC/MSCs hydrogel enhanced diabetes wound healing, rapid re-epithelization, favorable collagen deposition, and abundant wound angiogenesis. These findings demonstrated that the combined effects of SA, MnO2, RHC, and MSCs synergistically accelerate healing, resulting in a reduced healing time. These observed healing effects demonstrated the potential of this multifunctional hydrogel to transform chronic wound care and improve patient outcomes.


Assuntos
Hidrogéis , Compostos de Manganês , Células-Tronco Mesenquimais , Óxidos , Cicatrização , Cicatrização/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Animais , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Humanos , Óxidos/química , Óxidos/farmacologia , Diabetes Mellitus Experimental , Proliferação de Células/efeitos dos fármacos , Colágeno/química , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Alginatos/química , Alginatos/farmacologia , Masculino , Camundongos
17.
Toxicon ; 243: 107717, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38614245

RESUMO

Cancer-related pain is considered one of the most prevalent symptoms for those affected by cancer, significantly influencing quality of life and treatment outcomes. Morphine is currently employed for analgesic treatment in this case, however, chronic use of this opioid is limited by the development of analgesic tolerance and adverse effects, such as digestive and neurological disorders. Alternative therapies, such as ion channel blockade, are explored. The toxin Phα1ß has demonstrated efficacy in blocking calcium channels, making it a potential candidate for alleviating cancer-related pain. This study aims to assess the antinociceptive effects resulting from intravenous administration of the recombinant form of Phα1ß (r-Phα1ß) in an experimental model of cancer-related pain in mice, tolerant or not to morphine. The model of cancer-induced pain was used to evaluate these effects, with the injection of B16F10 cells, followed by the administration of the r-Phα1ß, and evaluation of the mechanical threshold by the von Frey test. Also, adverse effects were assessed using a score scale, the rotarod, and open field tests. Results indicate that the administration of r-Phα1ß provoked antinociception in animals with cancer-induced mechanical hyperalgesia, with or without morphine tolerance. Previous administration of r-Phα1ß was able to recover the analgesic activity of morphine in animals tolerant to this opioid. r-Phα1ß was proved safe for these parameters, as no adverse effects related to motor and behavioral activity were observed following intravenous administration. This study suggests that the concomitant use of morphine and r-Phα1ß could be a viable strategy for pain modulation in cancer patients.


Assuntos
Administração Intravenosa , Dor do Câncer , Tolerância a Medicamentos , Morfina , Animais , Morfina/administração & dosagem , Morfina/uso terapêutico , Morfina/farmacologia , Dor do Câncer/tratamento farmacológico , Camundongos , Analgésicos/uso terapêutico , Analgésicos/farmacologia , Venenos de Aranha , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/administração & dosagem , Masculino , Proteínas Recombinantes/uso terapêutico , Modelos Animais de Doenças , Hiperalgesia/tratamento farmacológico
18.
J Clin Immunol ; 44(5): 107, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676811

RESUMO

PURPOSE: Patients with adenosine deaminase 1 deficient severe combined immunodeficiency (ADA-SCID) are initially treated with enzyme replacement therapy (ERT) with polyethylene glycol-modified (PEGylated) ADA while awaiting definitive treatment with hematopoietic stem cell transplant (HSCT) or gene therapy. Beginning in 1990, ERT was performed with PEGylated bovine intestinal ADA (ADAGEN®). In 2019, a PEGylated recombinant bovine ADA (Revcovi®) replaced ADAGEN following studies in older patients previously treated with ADAGEN for many years. There are limited longitudinal data on ERT-naïve newborns treated with Revcovi. METHODS: We report our clinical experience with Revcovi as initial bridge therapy in three newly diagnosed infants with ADA-SCID, along with comprehensive biochemical and immunologic data. RESULTS: Revcovi was initiated at twice weekly dosing (0.2 mg/kg intramuscularly), and monitored by following plasma ADA activity and the concentration of total deoxyadenosine nucleotides (dAXP) in erythrocytes. All patients rapidly achieved a biochemically effective level of plasma ADA activity, and red cell dAXP were eliminated within 2-3 months. Two patients reconstituted B-cells and NK-cells within the first month of ERT, followed by naive T-cells one month later. The third patient reconstituted all lymphocyte subsets within the first month of ERT. One patient experienced declining lymphocyte counts with improvement following Revcovi dose escalation. Two patients developed early, self-resolving thrombocytosis, but no thromboembolic events occurred. CONCLUSION: Revcovi was safe and effective as initial therapy to restore immune function in these newly diagnosed infants with ADA-SCID, however, time course and degree of reconstitution varied. Revcovi dose may need to be optimized based on immune reconstitution, clinical status, and biochemical data.


Assuntos
Adenosina Desaminase , Agamaglobulinemia , Terapia de Reposição de Enzimas , Imunodeficiência Combinada Severa , Humanos , Adenosina Desaminase/deficiência , Adenosina Desaminase/genética , Imunodeficiência Combinada Severa/terapia , Lactente , Agamaglobulinemia/terapia , Masculino , Feminino , Recém-Nascido , Animais , Resultado do Tratamento , Reconstituição Imune , Proteínas Recombinantes/uso terapêutico
20.
Int J Med Sci ; 21(4): 703-713, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464833

RESUMO

Background: Renal anaemia and left ventricular hypertrophy are the main complications of chronic kidney disease and are shared among dialysis patients. This retrospective study aimed to compare the efficacies of the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat and recombinant human erythropoietin in reversing ventricular remodeling in dialysis patients with renal anaemia. Methods: A total of 204 participants underwent baseline examinations, including echocardiograms and laboratory tests, before being administered either treatment for at least 24 weeks from January 2018 to October 2021, after which follow-up examinations were conducted at 6 months. Propensity score matching based on key variables included age, gender, cardiovascular diseases, cardiovascular medications, dialysis course and the vascular access at baseline was performed to include populations with similar characteristics between groups. Results: In total, 136 patients were included with roxadustat or recombinant human erythropoietin. The left ventricular mass index after treatment with roxadustat and recombinant human erythropoietin both significantly decreased after 6 months, but there was no significant difference in the change in left ventricular mass index between the two groups. In addition, the left ventricular end-diastolic diameters and left ventricular wall thickness, systolic blood pressure, and diastolic blood pressure significantly decreased in the roxadustat group. Roxadustat and recombinant human erythropoietin also increased haemoglobin significantly, but there was no significant difference in the change in haemoglobin between the two groups. The results of multiple linear regression showed that the change in haemoglobin was independent factor affecting the improvement of left ventricular mass index. Conclusions: The increase of haemoglobin was associated with improving left ventricular hypertrophy in dialysis patients. However, the beneficial effects between roxadustat and recombinant human erythropoietin on left ventricular mass index did not show clear superiority or inferiority in six months.


Assuntos
Anemia , Eritropoetina , Insuficiência Renal Crônica , Humanos , Anemia/tratamento farmacológico , Anemia/etiologia , Eritropoetina/uso terapêutico , Glicina/uso terapêutico , Hemoglobinas/análise , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Isoquinolinas/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Estudos Retrospectivos , Remodelação Ventricular
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