Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.491.523
Filtrar
1.
Int. microbiol ; 27(1): 265-276, Feb. 2024. graf
Artigo em Inglês | IBECS | ID: ibc-230259

RESUMO

Background: Metformin (MET) is a first-line therapy for type-2 diabetes mellitus (T2DM). Liraglutide (LRG) is a glucagon-like peptide-1 receptor agonist used as a second-line therapy in combination with MET. Methods: We performed a longitudinal analysis comparing the gut microbiota of overweight and/or pre-diabetic participants (NCP group) with that of each following their progression to T2DM diagnosis (UNT group) using 16S ribosomal RNA gene sequencing of fecal bacteria samples. We also examined the effects of MET (MET group) and MET plus LRG (MET+LRG group) on the gut microbiota of these participants following 60 days of anti-diabetic drug therapy in two parallel treatment arms. Results: In the UNT group, the relative abundances of Paraprevotella (P = 0.002) and Megamonas (P = 0.029) were greater, and that of Lachnospira (P = 0.003) was lower, compared with the NCP group. In the MET group, the relative abundance of Bacteroides (P = 0.039) was greater, and those of Paraprevotella (P = 0.018), Blautia (P = 0.001), and Faecalibacterium (P = 0.005) were lower, compared with the UNT group. In the MET+LRG group, the relative abundances of Blautia (P = 0.005) and Dialister (P = 0.045) were significantly lower than in the UNT group. The relative abundance of Megasphaera in the MET group was significantly greater than in the MET+LRG group (P = 0.041). Conclusions: Treatment with MET and MET+LRG results in significant alterations in gut microbiota, compared with the profiles of patients at the time of T2DM diagnosis. These alterations differed significantly between the MET and MET+LRG groups, which suggests that LRG exerted an additive effect on the composition of gut microbiota.(AU)


Assuntos
Humanos , Diabetes Mellitus Tipo 2 , Metformina , Microbioma Gastrointestinal , Liraglutida/farmacologia , RNA Ribossômico 16S , Microbiologia , Técnicas Microbiológicas , China , Liraglutida/uso terapêutico
6.
Rev. esp. quimioter ; 37(1): 17-28, Feb. 2024.
Artigo em Inglês | IBECS | ID: ibc-230419

RESUMO

Despite having emerged from pandemic status, the incidence of COVID-19 episodes has recently increased in Spain, including pediatric cases and admissions to Intensive Care Units. Several recombinant variants are circulating among us, particularly XBB arising from two Omicron BA.2 sublineages with mutations in the genes encoding the spicule proteins that could increase binding to the ACE2 receptor and be more prone to immune escape. Faced with these, 3 pharmaceutical companies have developed vaccines adapted to the XBB.1.5 sublineage that are already available for administration in our setting with risks that should not be different from those of previous mRNA vaccines and with clearly favorable benefit/risk ratios. They should be applied to patients with potential for poor COVID-19 evolution and to collectives that have a particular relationship of proximity with them. Their application should be understood not only from a perspective of individual convenience but also from that of collective responsibility. The most convenient seems to be a simultaneous immunization of COVID-19 and influenza in our environment. In the therapeutic aspect, there is little to expect right now from antisera, but the already known antiviral drugs are still available and indicated, although their efficacy will have to be reevaluated due to their impact on populations that are mostly immunized and with a better prognosis than in the past. In our opinion, it is necessary to continue to make a reasonable and timely use of masks and other non-pharmacological means of protection. (AU)


Pese a haber salido de la situación de pandemia, la incidencia de episodios de COVID-19 ha aumentado recientemente en España, incluidos los casos pediátricos y los ingresos en Unidades de Cuidados Intensivos. Circulan entre nosotros diversas variantes recombinantes, particularmente la XBB surgidas de dos sublinajes Omicron BA.2 con mutaciones en los genes que codifican las proteínas de la espícula y que pudieran aumentar la unión al receptor ACE2 y ser más propensas al escape inmune. Frente a ellas, 3 empresas farmacéuticas han elaborado vacunas adaptadas al sublinaje XBB.1.5 que ya se encuentran disponibles para su administración en nuestro medio con riesgos que no deben ser diferentes a los de las vacunas mRNA previas y con relaciones beneficio/riesgos claramente favorables. Deben aplicarse a pacientes con potencial de mala evolución de COVID-19 y a los colectivos que tienen una particular relación de proximidad con ellos. Su aplicación debe ser entendida no sólo desde una perspectiva de conveniencia individual sino desde la de la responsabilidad colectiva. Lo más conveniente parece hacer una inmunización simultánea de COVID-19 y gripe en nuestro medio. En el aspecto terapéutico hay poco que esperar ahora mismo de los antisueros pero siguen estando disponibles e indicados los fármacos antivirales ya conocidos aunque su eficacia tendrá que reevaluarse por su impacto en poblaciones mayoritariamente inmunizadas y con pronóstico mejor que las de tiempos pasados. A nuestro juicio, es necesario seguir haciendo un uso razonable y puntual de mascarillas y otros medios no farmacológicos de protección. (AU)


Assuntos
Humanos , /prevenção & controle , /terapia , /instrumentação , /métodos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Máscaras , Vacinas/administração & dosagem , Vacinas/provisão & distribuição , Vacinas/uso terapêutico , Ritonavir
7.
Expert Rev Neurother ; 24(3): 291-298, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38299536

RESUMO

INTRODUCTION: An aripiprazole long-acting injectable (LAI) antipsychotic is now available for gluteal administration every 2 months via two different formulations: aripiprazole lauroxil (AL) and aripiprazole monohydrate (Ari 2MRTU). These longer dosing regimens of aripiprazole LAI offer new potential benefits for patients. AREAS COVERED: The authors review the evidence supporting the efficacy and safety of aripiprazole LAIs given every 2 months for the treatment of schizophrenia or bipolar disorder (BD) in adults. The article culminates with the authors' expert perspectives on the subject. EXPERT OPINION: AL 1064 mg every 2 months has established efficacy for the treatment of schizophrenia based on pharmacokinetic bridging studies and prospective data for treatment of an acute exacerbation of schizophrenia. In an open-label trial, Ari 2MRTU showed efficacy for the treatment of schizophrenia and BD type I based on pharmacokinetic parameters (comparable to aripiprazole once-monthly 400 mg); it also showed efficacy regarding the secondary endpoints. Multiple doses of AL 1064 mg or Ari 2MRTU 960 mg are generally well tolerated, in line with the safety profile of oral aripiprazole, with the exception of the injection-site reactions. While AL may require a 1-day initiation regimen, Ari 2MRTU 960 covers all the recommended doses of oral aripiprazole (10-20 mg).


Assuntos
Antipsicóticos , Transtorno Bipolar , Esquizofrenia , Adulto , Humanos , Aripiprazol/uso terapêutico , Esquizofrenia/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Estudos Prospectivos , Preparações de Ação Retardada/uso terapêutico
8.
Expert Rev Hematol ; 17(1-3): 95-100, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38299464

RESUMO

BACKGROUND: An accurate assessment of tumor viability after first-line treatment is critical for predicting treatment failure in peripheral T-cell lymphomas (PTCLs). 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been adopted as the preferred assessment method in clinical trials, but its impact in clinical practice should be examined. This study aims to determine the prognostic significance of18F-FDG-PET/CT for survival following first-line treatment in PTCL patients. RESEARCH DESIGN AND METHODS: Retrospective observational study including 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. RESULTS: Fifty patients were evaluated with18F-FDG-PET/CT following first-line therapy: 58% were18F-FDG-PET/CT-negative and 42% were18F-FDG-PET/CT-positive. Disease progression occurred in 37.9% of18F-FDG-PET/CT-negative patients and in 80.9% of18F-FDG-PET/CT-positive patients (p = 0.0037). Median progression-free survival and overall survival were 67 and 74 months for18F-FDG-PET/CT-negative patients, and 5 (p < 0.0001) and 10 months (p < 0.0001), respectively, in18F-FDG-PET/CT-positive patients. After multivariate analysis, only B symptoms emerged as a negative predictive factor of complete response (RR 7.08; 95% CI 1.60-31.31; p = 0.001). CONCLUSIONS: 18F-FDG-PET/CT identifies high-risk PTCL patients who will have poor prognosis and survival following first-line treatment. However, more research is needed to confirm the best treatment options for PTCL patients.


Assuntos
Linfoma de Células T Periférico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18/uso terapêutico , Prognóstico , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/tratamento farmacológico , Estudos Retrospectivos
9.
mSphere ; 9(2): e0058323, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38299852

RESUMO

Periprosthetic joint infection (PJI) after total joint arthroplasty is a major concern requiring multiple surgeries and antibiotic interventions. Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli are the predominant causes of these infections. Due to biofilm formation, antibiotic treatment for patients with PJI can prolong resistance, further complicating the use of current treatments. Previous research has shown that cathodic voltage-controlled electrical stimulation (CVCES) is an effective technique to prevent/treat implant-associated biofilm infections on titanium (Ti) surfaces. This study thus evaluated the efficacy of CVCES via the use of 10% betadine alone and in combination with CVCES to eradicate lab-grown biofilms on cemented and cementless cobalt-chromium (CoCr) and Ti surfaces. CVCES treatment alone for 24 hours demonstrated no detectable CFU for E. coli and P. aeruginosa biofilms on cementless CoCr implants. In the presence of cement, E. coli biofilms had 106 CFUs/implant remaining after CVCES treatment alone; however, P. aeruginosa biofilms on cemented implants were reduced to below detectable limits. The use of 10% betadine treatment for 3 minutes followed by 24-hour CVCES treatment brought CFU levels to below detectable limits in E. coli and P. aeruginosa. The same was true for S. aureus biofilms on cementless patellofemoral implants as well as femoral and tibial implants. These treatment methods were not sufficient for eradication of S. aureus biofilms on cemented implants. These results suggest that CVCES alone and CVCES with 10% betadine are effective approaches to treating biofilms formed by certain bacterial species potentially leading to the treatment of PJI.IMPORTANCEPeriprosthetic joint infections (PJIs) are problematic due to requiring multiple surgeries and antibiotic therapies that are responsible for increased patient morbidity and healthcare costs. These infections become resistant to antibiotic treatment due to the formation of biofilms on the orthopedic surfaces. Cathodic voltage-controlled electrical stimulation (CVCES) has previously been shown to be an effective technique to prevent and treat biofilm infections on different surfaces. This study shows that CVCES can increase the efficacy of 10% betadine irrigation used in debridement, antibiotics, and implant retention by 99.9% and clear infection to below detection limits. PJI treatments are at times limited, and CVCES could be a promising technology to improve patient outcomes.


Assuntos
Infecção Hospitalar , Infecções Relacionadas à Prótese , Humanos , Povidona-Iodo , Staphylococcus aureus , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/prevenção & controle , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Titânio , Estimulação Elétrica
10.
mSphere ; 9(2): e0057723, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38299868

RESUMO

Since 2016, in Colombia, ongoing transmission of Candida auris has been reported in multiple cities. Here, we provide an updated description of C. auris genomic epidemiology and the dynamics of antifungal resistance in Colombia. We sequenced 99 isolates from C. auris cases with collection dates ranging from June 2016 to January 2021; the resulting sequences coupled with 103 previously generated sequences from C. auris cases were described in a phylogenetic analysis. All C. auris cases were clade IV. Of the 182 isolates with antifungal susceptibility data, 67 (37%) were resistant to fluconazole, and 39 (21%) were resistant to amphotericin B. Isolates predominately clustered by country except for 16 isolates from Bogotá, Colombia, which grouped with isolates from Venezuela. The largest cluster (N = 166 isolates) contained two subgroups. The first subgroup contained 26 isolates, mainly from César; of these, 85% (N = 22) were resistant to fluconazole. The second subgroup consisted of 47 isolates from the north coast; of these, 81% (N = 38) were resistant to amphotericin B. Mutations in the ERG11 and TAC1B genes were identified in fluconazole-resistant isolates. This work describes molecular mechanisms associated with C. auris antifungal resistance in Colombia. Overall, C. auris cases from different geographic locations in Colombia exhibited high genetic relatedness, suggesting continued transmission between cities since 2016. These findings also suggest a lack of or minimal introductions of different clades of C. auris into Colombia. IMPORTANCE: Candida auris is an emerging fungus that presents a serious global health threat and has caused multiple outbreaks in Colombia. This work discusses the likelihood of introductions and local transmission of C. auris and provides an updated description of the molecular mechanisms associated with antifungal resistance in Colombia. Efforts like this provide information about the evolving C. auris burden that could help guide public health strategies to control C. auris spread.


Assuntos
Antifúngicos , Candidíase , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Anfotericina B , Candida auris , Fluconazol , Colômbia/epidemiologia , Candida/genética , Candidíase/microbiologia , Filogenia , Genômica
11.
Arch Orthop Trauma Surg ; 144(3): 1281-1287, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38305894

RESUMO

INTRODUCTION: Given the significant therapeutic gap for osteoporosis, this study aims to investigate the most common osteoporosis-related fracture. The analysis will also consider patients' serum vitamin D levels and the indications for basic osteoporosis diagnostic tests and osteoporosis therapy prior to fracture. MATERIALS AND METHODS: This prospective clinical trial included patients with distal radius fractures who underwent surgery at our hospital between 1 April 2021 and 7 April 2022. Blood samples were taken from all participants and existing risk factors for osteoporosis were recorded. In addition, the indication for a guideline-based osteoporosis diagnosis was assessed and the risk of another future fracture with FRAX® was calculated. This information was used to decide whether there was an indication for specific osteoporosis therapy. RESULTS: A diagnosis gap of 53% and a treatment gap of 84% were identified among the 102 patients investigated. The patients' ages ranged from 46 to 91 years, with an average vitamin D level of 57 nmol/l, which was below the recommended level of 75 nmol/l. It was noted on a monthly basis that the vitamin D level (without substitution) never exceeded the recommended value of 75 nmol/l in any month. Three-quarters of patients had indications for a baseline osteoporosis diagnosis, yet less than 50% received one. According to FRAX® data, 57% of patients had indications for specific osteoporosis treatment before experiencing the fracture. CONCLUSION: Even without a previous distal radius fracture, many patients are in need of osteoporosis diagnosis or treatment. Our research suggests that patients with distal radius fractures should have their vitamin D levels checked via a blood test and be evaluated for osteoporosis. As endogenous vitamin D levels are often inadequate, year-round vitamin D supplementation should be considered for the prevention of osteomalacia and as a basis for the treatment of osteoporosis. GERMAN CLINICAL TRIAL REGISTER ID: DRKS00028085.


Assuntos
Osteoporose , Fraturas por Osteoporose , Fraturas do Rádio , Fraturas do Punho , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Densidade Óssea , Osteoporose/diagnóstico , Fraturas por Osteoporose/tratamento farmacológico , Fraturas do Rádio/complicações , Fraturas do Rádio/terapia , Fatores de Risco , Vitamina D/uso terapêutico , Estudos Prospectivos
12.
Biofabrication ; 16(2)2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38306674

RESUMO

Glandular cancers are amongst the most prevalent types of cancer, which can develop in many different organs, presenting challenges in their detection as well as high treatment variability and failure rates. For that purpose, anticancer drugs are commonly tested in cancer cell lines grown in 2D tissue culture on plastic dishesin vitro, or in animal modelsin vivo. However, 2D culture models diverge significantly from the 3D characteristics of living tissues and animal models require extensive animal use and time. Glandular cancers, such as prostate cancer-the second leading cause of male cancer death-typically exist in co-centrical architectures where a cell layer surrounds an acellular lumen. Herein, this spatial cellular position and 3D architecture, containing dual compartments with different hydrogel materials, is engineered using a simple co-axial nozzle setup, in a single step utilizing prostate as a model of glandular cancer. The resulting hydrogel soft structures support viable prostate cancer cells of different cell lines and enable over-time maturation into cancer-mimicking aggregates surrounding the acellular core. The biofabricated cancer mimicking structures are then used as a model to predict the inhibitory efficacy of the poly ADP ribose polymerase inhibitor, Talazoparib, and the antiandrogen drug, Enzalutamide, in the growth of the cancer cell layer. Our results show that the obtained hydrogel constructs can be adapted to quickly obtain 3D cancer models which combine 3D physiological architectures with high-throughput screening to detect and optimize anti-cancer drugs in prostate and potentially other glandular cancer types.


Assuntos
Antineoplásicos , Neoplasias da Próstata , Humanos , Animais , Masculino , Hidrogéis/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Linhagem Celular
13.
Blood Cancer J ; 14(1): 24, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307865

RESUMO

Multiple myeloma is a genetically complex and heterogenous malignancy with a 5-year survival rate of approximately 60%. Despite advances in therapy, patients experience cycles of remission and relapse, with each successive line of therapy associated with poorer outcomes; therefore, therapies with different mechanisms of action against new myeloma antigens are needed. G protein-coupled receptor class C group 5 member D (GPRC5D) has emerged as a novel therapeutic target for the treatment of multiple myeloma. We review the biology and target validation of GPRC5D, and clinical data from early phase trials of GPRC5D-targeting bispecific antibodies, talquetamab and forimtamig, and chimeric antigen receptor T cell (CAR-T) therapies, MCARH109, OriCAR-017, and BMS-986393. In addition to adverse events (AEs) associated with T-cell-redirection therapies irrespective of target, a consistent pattern of dermatologic and oral AEs has been reported across several trials of GPRC5D-targeting bispecific antibodies, as well as rare cerebellar events with CAR-T therapy. Additional studies are needed to understand the underlying mechanisms involved in the development of skin- and oral-related toxicities. We review the strategies that have been used to manage these GPRC5D-related toxicities. Preliminary efficacy data showed overall response rates for GPRC5D-targeting T-cell-redirecting therapies were ≥64%; most responders achieved a very good partial response or better. Pharmacokinetics/pharmacodynamics showed that these therapies led to cytokine release and T-cell activation. In conclusion, results from early phase trials of GPRC5D-targeting T-cell-redirecting agents have shown promising efficacy and manageable safety profiles, including lower infection rates compared with B-cell maturation antigen- and Fc receptor-like protein 5-targeting bispecific antibodies. Further clinical trials, including those investigating GPRC5D-targeting T-cell-redirecting agents in combination with other anti-myeloma therapies and with different treatment modalities, may help to elucidate the future optimal treatment regimen and sequence for patients with multiple myeloma and improve survival outcomes. Video Summary.


Assuntos
Anticorpos Biespecíficos , Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Mieloma Múltiplo/tratamento farmacológico , Anticorpos Biespecíficos/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Imunoterapia Adotiva/métodos , Receptores Acoplados a Proteínas G
14.
Expert Rev Neurother ; 24(3): 235-249, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38315124

RESUMO

INTRODUCTION: Lennox-Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterized by treatment-refractory seizures, including tonic/atonic 'drop' seizures, and intellectual impairment and slow spike-wave discharges on the electroencephalogram. Fenfluramine, previously prescribed as a weight-loss drug but then withdrawn, has recently been approved in the US, EU, and UK for the adjunct treatment of seizures associated with LGS. AREAS COVERED: The authors review the efficacy and safety findings from clinical trials of fenfluramine in LGS. The authors then discuss the evidence for adverse effects that may be of particular concern to fenfluramine, namely cardiac abnormalities, and weight loss, in the context of the use of fenfluramine for the treatment of the refractory seizures in LGS. EXPERT OPINION: Fenfluramine has demonstrated efficacy in reducing the frequency of seizures in LGS, notably drop seizures, in short-term and long-term clinical trials. Valvular heart disease and pulmonary hypertension have not been reported at the low doses (≤26 mg/day) used in these studies, however, data are limited. Due to its novel mechanism of action, fenfluramine may be of benefit in LGS which has not responded adequately to other antiseizure medications. However, none of these medications, including fenfluramine, achieves the ultimate goal of seizure freedom in most cases.


Assuntos
Epilepsia Generalizada , Síndrome de Lennox-Gastaut , Humanos , Criança , Síndrome de Lennox-Gastaut/tratamento farmacológico , Fenfluramina/uso terapêutico , Convulsões/tratamento farmacológico , Eletroencefalografia , Epilepsia Generalizada/tratamento farmacológico , Anticonvulsivantes/uso terapêutico
15.
Phys Med Biol ; 69(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38316055

RESUMO

Photodynamic therapy (PDT) is an effective antimicrobial therapy that we used to treat human abscess cavities in a Phase 1 clinical trial. This trial included pre-PDT measurements of abscess optical properties, which affect light dose (light fluence) at the abscess wall and PDT response. This study simulated PDT treatment planning for 13 subjects that received optical spectroscopy prior to clinical PDT, to determine the impact of measured optical properties on ability to achieve fluence rate targets in 95% of the abscess wall. Retrospective treatment plans were evaluated for 3 conditions: (1) clinically delivered laser power and assumed, homogeneous optical properties, (2) clinically delivered laser power and measured, homogeneous optical properties, and (3) with patient-specific treatment planning using measured, homogeneous optical properties. Treatment plans modified delivered laser power, intra-cavity Intralipid (scatterer) concentration, and laser fiber type. Using flat-cleaved laser fibers, the proportion of subjects achieving 95% abscess wall coverage decreased significantly relative to assumed optical properties when using measured values for 4 mW cm-2(92% versus 38%,p= 0.01) and 20 mW cm-2(62% versus 15%,p= 0.04) thresholds. When measured optical properties were incorporated into treatment planning, the 4 mW cm-2target was achieved for all cases. After treatment planning, optimal Intralipid concentration across subjects was 0.14 ± 0.09%, whereas 1% was used clinically. Required laser power to achieve the 4 mW cm-2target was significantly correlated with measured abscess wall absorption (ρ= 0.7,p= 0.008), but not abscess surface area (ρ= 0.2,p= 0.53). When using spherical diffuser fibers for illumination, both optimal Intralipid concentration (p= 0.0005) and required laser power (p= 0.0002) decreased compared to flat cleaved fibers. At 0% Intralipid concentration, the 4 mW cm-2target could only be achieved for 69% of subjects for flat-cleaved fibers, compared to 100% for spherical diffusers. Based on large inter-subject variations in optical properties, individualized treatment planning is essential for abscess photodynamic therapy. (Clinical Trial Registration: The parent clinical trial from which these data were acquired is registered on ClinicalTrials.gov as 'Safety and Feasibility Study of Methylene Blue Photodynamic Therapy to Sterilize Deep Tissue Abscess Cavities,' with ClinicalTrials.gov identifier NCT02240498).


Assuntos
Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Iluminação , Abscesso/diagnóstico por imagem , Abscesso/tratamento farmacológico , Estudos Retrospectivos , Luz , Fármacos Fotossensibilizantes/uso terapêutico
16.
Nat Metab ; 6(2): 290-303, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38316982

RESUMO

Obesity is a major public health crisis. Multi-specific peptides have emerged as promising therapeutic strategies for clinical weight loss. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are endogenous incretins that regulate weight through their receptors (R). AMG 133 (maridebart cafraglutide) is a bispecific molecule engineered by conjugating a fully human monoclonal anti-human GIPR antagonist antibody to two GLP-1 analogue agonist peptides using amino acid linkers. Here, we confirm the GIPR antagonist and GLP-1R agonist activities in cell-based systems and report the ability of AMG 133 to reduce body weight and improve metabolic markers in male obese mice and cynomolgus monkeys. In a phase 1, randomized, double-blind, placebo-controlled clinical study in participants with obesity ( NCT04478708 ), AMG 133 had an acceptable safety and tolerability profile along with pronounced dose-dependent weight loss. In the multiple ascending dose cohorts, weight loss was maintained for up to 150 days after the last dose. These findings support continued clinical evaluation of AMG 133.


Assuntos
Peptídeo 1 Semelhante ao Glucagon , Camundongos , Animais , Humanos , Masculino , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Redução de Peso , Peptídeos/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/metabolismo
17.
Expert Rev Hematol ; 17(1-3): 47-54, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38319240

RESUMO

INTRODUCTION: Immunomodulatory drugs (IMiDs) are widely used in the management of newly diagnosed and relapsed/refractory multiple myeloma patients. These agents show their potential effect on myeloma bone disease (MBD), including inhibition of osteoclasts activity and effects on osteoblasts differentiation. It is unclear whether these effects are direct, which may have an impact on bone formation markers when combined with proteasome inhibitors. AREAS COVERED: This review summarizes the available evidence on the role of IMiDs in microenvironment regulation and their potential effects on bone metabolism. The literature search methodology consisted of searching PubMed for basic and clinical trials using medical subject terms. Included articles were screened and evaluated by the coauthors of this review. EXPERT OPINION: As a therapeutic option, IMiDs directly affect preosteoblast/osteoclast differentiation. The combination of proteasome inhibitors may counteract the short-term up-regulation of osteogenic activity markers, and therefore intravenous zoledronic acid is recommended, however, obtaining a more significant myeloma response will have a long-term positive impact on myeloma bone disease.


Assuntos
Doenças Ósseas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Inibidores de Proteassoma/farmacologia , Inibidores de Proteassoma/uso terapêutico , Agentes de Imunomodulação , Osteoclastos , Doenças Ósseas/tratamento farmacológico , Doenças Ósseas/etiologia , Microambiente Tumoral
18.
JAMA Netw Open ; 7(2): e2354916, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38319661

RESUMO

Importance: Intracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) use carries extremely high morbidity and mortality. The clinical effectiveness of hemostatic therapy is unclear. Objective: To compare the clinical and radiological outcomes of DOAC-associated ICH treated with prothrombin complex concentrate (PCC) vs conservative management. Design, Setting, and Participants: In this population-based, propensity score-weighted retrospective cohort study, patients who developed DOAC-associated ICH from January 1, 2016, to December 31, 2021, in Hong Kong were identified. The outcomes of patients who received 25 to 50 IU/kg PCC with those who received no hemostatic agents were compared. Data were analyzed from May 1, 2022, to June 30, 2023. Main Outcomes and Measures: The primary outcome was modified Rankin scale of 0 to 3 or returning to baseline functional status at 3 months. Secondary outcomes were mortality at 90 days, in-hospital mortality, and hematoma expansion. Weighted logistic regression was performed to evaluate the association of PCC with study outcomes. In unweighted logistic regression models, factors associated with good neurological outcome and hematoma expansion in DOAC-associated ICH were identified. Results: A total of 232 patients with DOAC-associated ICH, with a mean (SD) age of 77.2 (9.3) years and 101 (44%) female patients, were included. Among these, 116 (50%) received conservative treatment and 102 (44%) received PCC. Overall, 74 patients (31%) patients had good neurological recovery and 92 (39%) died within 90 days. Median (IQR) baseline hematoma volume was 21.7 mL (3.6-66.1 mL). Compared with conservative management, PCC was not associated with improved neurological recovery (adjusted odds ratio [aOR], 0.62; 95% CI, 0.33-1.16; P = .14), mortality at 90 days (aOR, 1.03; 95% CI, 0.70-1.53; P = .88), in-hospital mortality (aOR, 1.11; 95% CI, 0.69-1.79; P = .66), or reduced hematoma expansion (aOR, 0.94; 95% CI, 0.38-2.31; P = .90). Higher baseline hematoma volume, lower Glasgow coma scale, and intraventricular hemorrhage were associated with lower odds of good neurological outcome but not hematoma expansion. Conclusions and Relevance: In this cohort study, Chinese patients with DOAC-associated ICH had large baseline hematoma volumes and high rates of mortality and functional disability. PCC treatment was not associated with improved functional outcome, hematoma expansion, or mortality. Further studies on novel hemostatic agents as well as neurosurgical and adjunctive medical therapies are needed to identify the best management algorithm for DOAC-associated ICH.


Assuntos
Fatores de Coagulação Sanguínea , Tratamento Conservador , Hemostáticos , Humanos , Feminino , Idoso , Masculino , Estudos de Coortes , Estudos Retrospectivos , Fator IX , Hemostáticos/uso terapêutico , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/tratamento farmacológico , Hematoma/induzido quimicamente , Hematoma/tratamento farmacológico , Anticoagulantes/efeitos adversos
20.
Nat Rev Rheumatol ; 20(3): 170-181, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38321298

RESUMO

In the past two decades, the treatment of juvenile idiopathic arthritis (JIA) has evolved markedly, owing to the availability of a growing number of novel, potent and relatively safe therapeutic agents and the shift of management strategies towards early achievement of disease remission. However, JIA encompasses a heterogeneous group of diseases that require distinct treatment approaches. Furthermore, some old drugs, such as methotrexate, sulfasalazine and intraarticular glucocorticoids, still maintain an important therapeutic role. In the past 5 years, information on the efficacy and safety of drug therapies for JIA has been further enriched through the accomplishment of several randomized controlled trials of newer biologic and synthetic targeted DMARDs. In addition, a more rational therapeutic approach has been fostered by the promulgation of therapeutic recommendations and guidelines. A multinational collaborative effort has led to the development of the recommendations for the treat-to-target strategy in JIA. There is currently increasing interest in establishing the optimal time and modality for discontinuation of treatment in children with JIA who achieve sustained clinical remission. The aim of this Review is to summarize the current evidence and discuss the therapeutic approaches to the management of non-systemic phenotypes of JIA, including oligoarthritis, polyarthritis, enthesitis-related arthritis and psoriatic arthritis.


Assuntos
Antirreumáticos , Artrite Juvenil , Artrite Psoriásica , Criança , Humanos , Artrite Juvenil/tratamento farmacológico , Antirreumáticos/uso terapêutico , Metotrexato/uso terapêutico , Sulfassalazina/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...