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1.
Artículo en Inglés | MEDLINE | ID: mdl-38759208

RESUMEN

OBJECTIVES: To investigate whether hypoechoic wall thickness is influenced by the systole or diastole moment in the cardiac cycle and if this can influence ultrasound (US) assessments of giant cell arteritis (GCA). METHODS: US videos of 100 consecutive patients (50 with GCA, 50 without) performed between January 2021 and June 2023 were reviewed. Intima-media thickness (IMT) of temporal (including common trunk, frontal and parietal branches), axillary and subclavian arteries were measured at two different time points, at systolic peak (SP) and at the end-diastole (ED). Differences between SP IMT and ED IMT, as well as in the halo count (HC) and in the OMERACT GCA Ultrasonography Score (OGUS) between these two times, were analyzed. RESULTS: IMT was significantly higher (4.8-5%) at ED in all arteries, in both GCA and non-GCA groups. HC and OGUS were also higher in ED in both groups. In 4 non-GCA patients (8%), the HC was positive in ED and negative in SP; in all of them the HC in ED was 1. In the GCA group, the timing of the cardiac cycle did not influence the final US diagnosis; however, it did modify the HC in 14 patients (28%). CONCLUSION: IMT can fluctuate during the cardiac cycle, with higher measurements occurring at ED. This variability could potentially impact the accuracy of US diagnoses and assessments of GCA. If further research corroborates these findings, it may be imperative to revise the guidelines for employing US in diagnosing GCA in order to incorporate these nuanced aspects.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38718182

RESUMEN

OBJECTIVE: To determine whether the OMERACT giant cell arteritis (GCA) Ultrasonography (US) Score (OGUS) change after treatment can be used for assessing the probability of relapse. METHODS: Multicenter retrospective study of GCA patients referred to two US GCA fast-track clinics over 2 years. Patients underwent US evaluation at baseline, 3 and 6 months. EULAR definitions for remission and relapse were checked at 3 and 6 months. OGUS changes at 0-3 months and 0-6 months were compared among patients with and without relapse at 6 months, as well as those with and without remission at 6 months. RESULTS: A total of 76 patients were included (mean age 77.2 years, 55.3% females). Nineteen (26%) patients relapsed at 6-months, of whom 14(19.1%) showed a minor relapse. EULAR remission at 6 months was achieved by 32(43.8%) patients. The standardized mean difference of OGUS between baseline and 3 and 6 months was -0.25 and -0.38, respectively. OGUS significantly improved between baseline and 6 months (1.18 vs 0.99,p=0.004) and from 3-6 months (1.08 vs 0.99,p=0.04) in non-relapsing patients, whereas no significant changes at 3 (1.17 vs 1.17;p=0.736) and 6 (1.17 vs 1.21;p=0.343) months were observed in those who experienced relapse. Mean 0-6-month OGUS improvement was lower in patients who relapsed (-0.1 vs 0.16,p=0.037). Mean 0-6-month OGUS improvement was greater in patients who achieved remission at 6 months (0.28vs -0.07,p=0.001). CONCLUSIONS: The absence of OGUS improvement during follow-up in GCA may be used to assess the probability of relapse and the absence of remission at 6 months.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38321365

RESUMEN

OBJECTIVE: CD4+CXCR5+PD-1hi follicular helper T (Tfh) cells dwell in the germinal centers (GCs) of lymphoid organs and participate in Rheumatoid Arthritis (RA) pathogenesis; the frequency of their circulating counterparts (cTfh-frequency) is expanded in RA and correlates with the pool of GC Tfh cells. Our objective was to study the effect of abatacept (ABT) or TNF blockers (TNFb) on the cTfh-frequency in RA. METHODS: Peripheral blood was drawn from seropositive-longstanding RA patients chronically receiving csDMARDS (n = 45), TNFb (n = 59), or ABT (n = 34), and healthy controls (HC) (n = 137). Also, patients with an incomplete response to csDMARDS (n = 41) who initiated TNFb (n = 19) or ABT (n = 22), were studied at 0 and 12 months. The cTfh-frequency was examined by cytometry. RESULTS: As compared with HC, an increased cTfh-frequency was seen in seropositive-longstanding RA chronically receiving csDMARDs or TNFb but not ABT. After escalating from csDMARDs, the cTfh-frequency did not vary in patients who were given TNFb but decreased to HC levels in those given ABT. In the ABT group, the baseline cTfh-frequency was higher for patients who attained 12M remission (12Mr), vs those who remained active (12Ma): 0m cutoff for remission >0.38% (Sens. 92%, Sp. 90%), OR 25.3. Conversely, in the TNFb group, the baseline cTfh-frequency was lower for 12Mr vs 12Ma: 0m cutoff for non-remission >0.44% (Sens. 67%, Sp. 90%), OR 8.5. CONCLUSION: ABT but not TNFb, is able to curtail the cTfh-frequency in RA. A higher baseline cTfh-frequency predicts a good response to ABT but a poor response to TNFb.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38244610

RESUMEN

OBJECTIVE: To determine the prevalence and predictive factors of visual manifestations in a large registry of patients with GCA. METHODS: ARTESER is a large Spanish multicentre registry supported by the Spanish Society of Rheumatology. It includes patients with GCA from across the entire country diagnosed between June 2013 and March 2019. The variables collected at diagnosis were demographics, clinical manifestations (including all visual manifestations), laboratory, temporal artery biopsy, and imaging findings (ultrasound, FDG-PET/CT, MRI angiography, CT angiography). Patients with and without visual involvement were compared in a bivariate analysis. Multivariate logistic regression was performed to determine potential predictive factors of visual manifestations. RESULTS: The study population comprised 1636 GCA patients, of whom 599 (36.6%) presented visual manifestations. Anterior ischemic optic neuropathy was the most frequent (n = 274 of 599; 45.7%) ocular complication. The independent predictors that increased the risk (OR; 95% confidence interval) of visual involvement were older age (1.027; 1.009-1.045) and jaw claudication (1.724; 1.325-2.243). The variables associated with a reduced risk were polymyalgia rheumatica (0.541; 0.414-0.708), fever (0.373; 0.264-0.527), longer symptom duration (0.946; 0.909-0.985), and higher erythrocyte sedimentation rate (ESR) (0.992; 0.988-0.997), common features of patients with large vessel-GCA. CONCLUSION: One-third of GCA patients present visual manifestations at diagnosis. Older age and jaw claudication are independent predictors of visual manifestations, whereas polymyalgia rheumatica, fever, longer symptom duration, and high ESR reduce the risk of visual involvement.

5.
Chemistry ; 30(37): e202401215, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38688855

RESUMEN

The coordination of anionic donors is involved at various stages of catalytic cycles in transition-metal catalysis, but control over the spatial positioning of anions around a metal center is a challenge in coordination chemistry. Here we show that regioisomeric phosphine-carboxylate ligands provide spatial anion control on palladium(II) centers by favoring either κ2, cis-κ1, or trans-κ1 coordination of the carboxylate donor. Additionally, the palladium(II) carboxylates, which contain a methyl donor, upon protonation, deliver metal-alkyl complexes that feature a coordinated carboxylic acid. Such complexes can be considered as models for the minima that follow the concerted metalation-deprotonation transition state for C-H activation. The predictability of the coordination modes is further demonstrated on silver(I) and copper(I) centers, for which less common structures of mononuclear and dinuclear complexes can be obtained by using spatial anion control. Our results demonstrate the potential for spatial control over carboxylate anions in coordination chemistry.

6.
Clin Exp Rheumatol ; 42(5): 999-1005, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38197184

RESUMEN

OBJECTIVES: Certolizumab pegol (CZP), an Fc-free antibody fragment, has shown stable serum levels and steady efficacy in the treatment of RA patients, irrespective of RF levels at baseline. Here, we examine, in clinical practice, the effect of baseline RF and ACPA levels on serum drug levels of IFX, ADL and CZP an Fc-free antibody fragment. METHODS: This is a retrospective study performed in real-world patients. We assessed 170 patients with RA: 90 (53%) received IFX, 48 (28%) ADL and 32 (19%) CZP. Demographic and clinical variables, RF and ACPA levels were obtained at the baseline visit (T0), and patients were stratified based on negative, low, medium, or high levels. After 6 months (T6) serum drug levels and anti-drug antibodies (ADAb), were computed. RESULTS: While CZP serum levels did not differ across RF groups at T6, high baseline RF was linked to lower serum drug levels compared to RF negative status in treatment with complete monoclonal antibodies IFX and ADL. No differences in disease activity measured by DAS28 at baseline were observed across RF quartiles in patients treated with IFX or ADL. ADAb was observed in 26 patients with IFX, 3 with ADL and 1 with CZP, following 6 months of treatment. Patients with high baseline RF levels dropped out more frequently by secondary non-response in IFX or ADL than CZP (80% vs. 75% vs. 33%, p=0.002). CONCLUSIONS: In this real word data evaluation, CZP serum levels were independent of RF levels in patients however patients with high baseline RF levels who obtained IFX or ADL had lower serum drug levels at 6 months than baseline RF-negative patients. In addition, secondary non-response was more frequent in patients with high RF levels treated with IFX and ADL.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Certolizumab Pegol , Factor Reumatoide , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Artritis Reumatoide/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factor Reumatoide/sangre , Certolizumab Pegol/uso terapéutico , Certolizumab Pegol/sangre , Anciano , Antirreumáticos/uso terapéutico , Antirreumáticos/sangre , Resultado del Tratamiento , Anticuerpos Antiproteína Citrulinada/sangre , Adulto , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/sangre , Infliximab/sangre , Infliximab/uso terapéutico , Infliximab/inmunología , Monitoreo de Drogas/métodos , Biomarcadores/sangre , Factores de Tiempo
7.
Clin Exp Rheumatol ; 41(5): 1114-1119, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36377568

RESUMEN

OBJECTIVES: Multiple failures to biologic or targeted specific disease-modifying anti-rheumatic drugs (b/tsDMARDs) that lead to difficult-to-treat rheumatoid arthritis (D2TRA) may be the result of multi-drug inefficacy or reflect treatment problems related to adverse events, comorbidities, and/or poor adherence. We aimed to characterise a cohort of D2TRA patients in clinical practice, to analyse the differences between D2TRA due to inefficacy versus D2TRA from other causes, and to compare them with non-D2TRA. METHODS: The D2TRA group included patients who were receiving ≥2b/tsDMARDs due to inefficacy (D2TRA-inef cacy) or because of adverse events, poor adherence, contraindications, comorbidities, drug-intolerance, etc. (D2TRA-other). Patients who achieved low disease activity or remission with the rst bDMARD were classified as non-D2TRA patients. For all patients, demographic, clinical characteristics and laboratory parameters were assessed prior to starting the rst b/tsDMARD. Descriptive analysis was performed and bivariate logistic regression models were assembled. RESULTS: In total, 253 patients were included: 131 non-D2TRA and 122 D2TRA [86 (70.5%) D2TRA-inefficacy and 36 (29.5%) D2TRA-other]. Comparison of the two groups of D2TRA patients: no differences in gender, age at start of b/tsDMARD or age at RA diagnosis were found; this was also true of socioeconomic status, frequency of anxiety-depression and other comorbidities. Patients categorised as D2TRA-other had less extra-articular manifestations than D2TRA-inef cacy, as well as lower values of DAS28 at the start of the rst b/tsDMARD. Comparisons of Non-D2TRA patients versus D2TRA-other resulted in the following observations: no differences in sociodemographic characteristics were evident nor were there any differences in terms of disease activity. CONCLUSIONS: Patients with D2TRA-other are indistinguishable from non-D2TRA patients at baseline, indicating the former cohort does not appear to have any predictive value during the early stages of b/tsDMARD treatment, unlike what occurs in patients with D2TRA-inefficacy.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Humanos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Antirreumáticos/efectos adversos , Comorbilidad , Productos Biológicos/uso terapéutico
8.
J Am Chem Soc ; 142(45): 19040-19046, 2020 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-33125849

RESUMEN

C-H arylation of arenes without the use of directing groups is a challenge, even for simple molecules, such as benzene. We describe spatial anion control as a concept for the design of catalytic sites for C-H bond activation, thereby enabling nondirected C-H arylation of arenes at ambient temperature. The mild conditions enable late-stage structural diversification of biologically relevant small molecules, and site-selectivity complementary to that obtained with other methods of arene functionalization can be achieved. These results reveal the potential of spatial anion control in transition-metal catalysis for the functionalization of C-H bonds under mild conditions.

9.
Rheumatology (Oxford) ; 59(9): 2443-2447, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-31953951

RESUMEN

OBJECTIVES: To describe the frequency and causes for the presence of a halo sign on the ultrasound of patients without a diagnosis of GCA. METHODS: In total, 305 patients with temporal artery colour Doppler ultrasound showing the presence of halo sign (intima-media thickness ≥0.34 mm for temporal arteries [TAs] and ≥1 mm for axillary arteries) were included, and their medical records were reviewed. The clinical diagnosis based on the evolution of the patient over at least one year was established as the definitive diagnosis. RESULTS: Fourteen of the 305 (4.6%) patients included showed presence of the halo sign without final diagnosis of GCA: 12 patients in the TAs (86%), and two patients with isolated AAs involvement (14%). Their diagnoses were PMR (n = 4, 29%); atherosclerosis (n = 3, 21%); and non-Hodgkin lymphoma type T, osteomyelitis of the skull base, primary amyloidosis associated with multiple myeloma, granulomatosis with polyangiitis, neurosyphilis, urinary sepsis and narrow-angle glaucoma (n = 1 each, 7%). CONCLUSION: The percentage of halo signs on the ultrasound of patients without GCA is low, but it does exist. There are conditions that may also show the halo sign (true positive halo sign), and we must know these and always correlate the ultrasound findings with the patient's clinic records.


Asunto(s)
Grosor Intima-Media Carotídeo/estadística & datos numéricos , Arteritis de Células Gigantes/diagnóstico por imagen , Ultrasonografía Doppler en Color/estadística & datos numéricos , Anciano , Reacciones Falso Positivas , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Arterias Temporales/diagnóstico por imagen
10.
Rev Gastroenterol Peru ; 39(4): 370-373, 2019.
Artículo en Español | MEDLINE | ID: mdl-32097400

RESUMEN

Necrotizing enterocolitis in adults (ECNA) is a disease of uncertain etiology, very rare, with very few cases described in the literature and with high mortality. There is a strong correlation between vascular and infectious events involved in the pathogenesis of massive intestinal necrosis in this entity.


Asunto(s)
Enterocolitis Necrotizante/etiología , Isquemia Mesentérica/complicaciones , Enterocolitis Necrotizante/diagnóstico por imagen , Resultado Fatal , Hemoperitoneo/diagnóstico por imagen , Humanos , Masculino , Isquemia Mesentérica/diagnóstico por imagen , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
11.
Rev Med Suisse ; 19(845): 1856, 2023 10 11.
Artículo en Francés | MEDLINE | ID: mdl-37819187
12.
J Am Chem Soc ; 139(4): 1428-1431, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28112916

RESUMEN

The use of α-cationic phosphonites derived from TADDOL as ancillary ligands has allowed a highly regio- and enantioselective synthesis of substituted [6]carbohelicenes by sequential Au-catalyzed intramolecular hydroarylation of diynes. Key for these results is the modular structure of these new ligands, and the enhanced reactivity that they impart to Au(I)-centers after coordination.

13.
Cytotherapy ; 19(8): 927-936, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28662983

RESUMEN

BACKGROUND AIMS: Despite the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the procedure is still associated with high toxicity in patients with refractory graft-versus-host disease (GvHD). Mesenchymal stromal cells (MSCs) are a new mode of therapy in the context of allo-HSCT. The objective of this study was to evaluate the safety and feasibility of the use of adipose tissue-derived MSCs (AT-MSCs) in patients with chronic GvHD. METHODS: Fourteen patients with moderate (n = 7) or severe (n = 7) chronic GvHD received 1 × 106/kg (group A, n = 9) or 3 × 106/kg (group B, n = 5) AT-MSCs with cyclosporine and prednisone as first-line therapy. RESULTS: Ten of the 14 patients were able to continue under the protocol: 80% were in complete remission, and 100% were off of steroids at week 56. The remaining 4 patients either worsened from chronic GvHD (n = 3) or abandoned the study (n = 1). At the end of the study, 11 of 14 patients are alive (overall survival 71.4%, median survival of 45.3 weeks). No suspected unexpected serious adverse reactions occurred during the trial. Neither relapse of underlying disease nor mortality due to infection was observed in this cohort. Biological studies showed increased CD19, CD4 and tumor necrosis factor-α with a temporary decrease in natural killer cells. DISCUSSION: AT-MSCs, in combination with immunosuppressive therapy, may be considered feasible and safe and likely would have an impact on the course of chronic GvHD. More studies are warranted to understand the potential benefits of AT-MSCs in these patients.


Asunto(s)
Tejido Adiposo/citología , Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Adulto , Ciclosporina/uso terapéutico , Femenino , Humanos , Inmunosupresores/uso terapéutico , Células Asesinas Naturales , Masculino , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Células Madre Mesenquimatosas , Persona de Mediana Edad , Prednisona/uso terapéutico , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/metabolismo
14.
Am J Hematol ; 91(7): 700-4, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27074204

RESUMEN

Multiple myeloma is a heterogeneous disease with variable survival; this variability cannot be fully explained by the current systems of risk stratification. Early mortality remains a serious obstacle to further improve the trend toward increased survival demonstrated in recent years. However, the definition of early mortality is not standardized yet. Importantly, no study has focused on the impact of comorbidity on early mortality in multiple myeloma to date. Therefore, we analyzed the role of baseline comorbidity in a large population-based cohort of 621 real-life myeloma patients over a 31-year period. To evaluate early mortality, a sequential multivariate regression model at 2, 6, and 12 months from diagnosis was performed. It was demonstrated that comorbidity had an independent impact on early mortality, which is differential and time-dependent. Besides renal failure, respiratory disease at 2 months, liver disease at 6 months, and hepatitis virus C infection at 12 months, were, respectively, associated with early mortality, adjusting for other well-established prognostic factors. On the other hand, the long-term monitoring in our study points out a modest downward trend in early mortality over time. This is the first single institution population-based study aiming to assess the impact of comorbidity on early mortality in multiple myeloma. It is suggested that early mortality should be analyzed at three key time points (2, 6, and 12 months), in order to allow comparisons between studies. Comorbidity plays a critical role in the outcome of myeloma patients in terms of early mortality. Am. J. Hematol. 91:700-704, 2016. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Mieloma Múltiple/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Comorbilidad , Humanos , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Sistema de Registros , Factores de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Adulto Joven
15.
Ann Pharmacother ; 49(9): 986-94, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26160968

RESUMEN

BACKGROUND: Transplantation-associated thrombotic microangiopathy (TA-TMA) is a rare complication of hematopoietic stem cell transplantation. Because sirolimus (SIR) and calcineurin inhibitor-either cyclosporine (CsA) or tacrolimus-have become more common as graft-versus-host disease (GVHD) prophylaxis, we are witnessing a higher frequency of this complication. OBJECTIVE: To analyze the incidence, timing, and management of TA-TMA in patients who received the combination of CsA and SIR as therapy for uncontrolled GVHD in one single center. METHODS: This was a retrospective analysis from February 2002 to June 2014 of the combination of SIR and CsA as salvage therapy in 61 patients with treatment-refractory or relapsed acute GVHD (n = 24) or chronic GVHD (n = 37) in a tertiary hospital. RESULTS: A total of 61 patients received CsA and SIR as salvage therapy for acute (n = 16), late acute (n = 8), overlap syndrome (n = 22), or classic chronic (n = 15) GVHD. We identified 13 patients with TA-TMA (21.3%), and the status of GVHD was active in 11 of 13 patients. Only 1 patient showed high CsA levels, and 6 of 13 patients had very high concentrations of SIR in blood. We used an enzyme inducer in 6 patients, which proved effective in 3. Overall survival for TA-TMA patients was inferior compared to that for non TA-TMA patients at 12 months (42.9% vs 51.9%) and 24 months (34.3% vs 49.1%), although this difference was not significant. CONCLUSION: Prompt identification and good management of TA-TMA, with better control of GVHD, may contribute to a decrease in patient mortality that would result from this complication.


Asunto(s)
Inhibidores de la Calcineurina/uso terapéutico , Ciclosporina/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunosupresores/uso terapéutico , Terapia Recuperativa , Sirolimus/uso terapéutico , Microangiopatías Trombóticas/tratamiento farmacológico , Enfermedad Aguda , Adulto , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Incidencia , Masculino , Recurrencia , Estudios Retrospectivos , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/mortalidad
17.
Nat Neurosci ; 27(9): 1783-1793, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38965445

RESUMEN

The role of the striatum in motor control is commonly assumed to be mediated by the two striatal efferent pathways characterized by striatal projection neurons (SPNs) expressing dopamine (DA) D1 receptors or D2 receptors (D1-SPNs and D2-SPNs, respectively), without regard to SPNs coexpressing both receptors (D1/D2-SPNs). Here we developed an approach to target these hybrid SPNs in mice and demonstrate that, although these SPNs are less abundant, they have a major role in guiding the motor function of the other two populations. D1/D2-SPNs project exclusively to the external globus pallidus and have specific electrophysiological features with distinctive integration of DA signals. Gain- and loss-of-function experiments indicate that D1/D2-SPNs potentiate the prokinetic and antikinetic functions of D1-SPNs and D2-SPNs, respectively, and restrain the integrated motor response to psychostimulants. Overall, our findings demonstrate the essential role of this population of D1/D2-coexpressing neurons in orchestrating the fine-tuning of DA regulation in thalamo-cortico-striatal loops.


Asunto(s)
Cuerpo Estriado , Neuronas , Receptores de Dopamina D1 , Receptores de Dopamina D2 , Animales , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Cuerpo Estriado/metabolismo , Ratones , Neuronas/metabolismo , Masculino , Ratones Transgénicos , Ratones Endogámicos C57BL , Actividad Motora/fisiología , Actividad Motora/efectos de los fármacos , Vías Nerviosas/fisiología , Vías Nerviosas/metabolismo , Femenino , Globo Pálido/metabolismo
18.
Viruses ; 16(2)2024 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-38400035

RESUMEN

The continuous pharmacological advances in antiretroviral treatment (ART) and the increasing understanding of HIV drug resistance has led to a change in the paradigm of ART optimization in the setting of the viral suppression of treatment-experienced patients with the emerging evidence of the effectiveness and safety of dual therapies. The aim of this study is to determine the antiviral efficacy and safety of switching to Dolutegravir + Lamivudine in people living with HIV, and to analyze the rate of patients with virologic failure (VF). A total of 200 patients were included with a median age of 51 years, 189 cells/µL of nadir CD4+, 13 years on ART and four previous ART regimens. Among the 168 patients who completed a follow-up at 48 weeks, a total of five VFs occurred, resulting in a 2.98% (5/168) VF rate. The results of the intention-to-treat analysis were a VF rate of 2.54% (5/197), and the rate of patients/year with viral suppression was 98.3% (298/303) in the observed data analysis. We observed a significant improvement in mean CD4 lymphocytes, the CD4/CD8 ratio and lipid profiles. The optimization of ART to DTG plus 3TC is a cost-effective switch option for treatment-experienced HIV patients, and also improves their lipid profiles.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Oxazinas , Piperazinas , Piridonas , Humanos , Persona de Mediana Edad , Lamivudine/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , España , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Antirretrovirales/uso terapéutico , Lípidos
19.
Clin Rheumatol ; 43(9): 2817-2823, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39009920

RESUMEN

OBJECTIVES: To evaluate the survival of different biologic or targeted-synthetic disease-modifying antirheumatic drugs (b/tsDMARD) administered after fulfilling difficult-to-treat rheumatoid arthritis (D2TRA) criteria, and to assess factors related to treatment discontinuation. METHODS: Retrospective study including D2TRA patients. Drug retention of the b/tsDMARD administered after fulfilling D2TRA was assessed by Kaplan-Meier plots and the log-rank test. Cox hazard models were used to identify factors affecting treatment discontinuation. RESULTS: Of the 122 patients included, 75 maintained active treatment (61.5%) with a subsequent line after D2T compared to 47 (38.5%) who discontinued and required more successive lines of b/tsDMARDs. The median survival of the treatments was 78.3(7.6) months and the treatment after D2T with the better rate of survival was rituximab, followed by JAKi and IL6Ri, while worse survival rates were associated with abatacept and TNFi. Significant differences were noted among b/tsDMARDs (log-rank p < 0.01) and to evaluate these differences, a Cox regression was performed, taking each b/tsDMARD as a reference and comparing it with the others. DAS28 values 6-months after initiation of treatment were higher in those patients who discontinued treatment [4.4(1.2) vs 3.5(1.3), p = 0.01]. The multivariate cox regression model revealed that treatment choice after D2T [HR = 1.26(95%CI 1.06-1.05)] and lower DAS28 values at 6 months [HR = 1.49(95%CI 1.16-1.52)] were independent risk factors associated with treatment discontinuation. CONCLUSIONS: Once patients met the D2TRA criteria, the subsequent line of b/tsDMARDs with the best survival rates were rituximab, JAKi and IL6Ri. Moreover, DAS28 at 6-months of treatment after D2T was an independent risk factor for drug discontinuation. Key Points • Rituximab, IL6Ri and JAKi have better retention rates in patients after fulfilling D2TRA criteria • Clinical disease activity in the first six months after fulfillment of D2TRA criteria is an independent risk factor of subsequent treatment survival.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/mortalidad , Femenino , Antirreumáticos/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Productos Biológicos/uso terapéutico , Adulto , Modelos de Riesgos Proporcionales , Estimación de Kaplan-Meier , Abatacept/uso terapéutico , Rituximab/uso terapéutico , Resultado del Tratamiento , Análisis de Supervivencia
20.
BMC Public Health ; 13: 1093, 2013 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-24274101

RESUMEN

BACKGROUND: Gonorrhoea infection is one of the most common bacterial sexually transmitted infections and an important cause of morbidity and serious complications. The objectives of this paper are: a) to describe gonorrhoea cases diagnosed in a network of 15 (out of 16) STI clinics in Spain during 2006-2010; b) to analyse differences among men who have sex with men (MSM), men who have sex exclusively with women (MSW) and women; and c) to evaluate factors associated to with HIV co-infection. METHODS: All gonorrhoea cases diagnosed in the network were included (25.7% of total cases notified in Spain). Data were collected by clinical staff. Descriptive/bivariate analyses were carried out stratifying by sex and transmission category; association and trends were evaluated using the chi-square test. Factors associated with HIV co-infection were estimated using a logistic regression model. RESULTS: 2385 cases were included: 55.3% among MSM, 31.3% among MSW and 13.3% among females; cases among MSM increased from 55.8% in 2006 to 62.9% in 2010 while no trends were found among the other two groups.Most MSM cases were Spaniards (72%), aged 25-34 years (46%), 49% reported previous STI and 25% concurrent STI (excluding HIV); casual partners were the commonest source of infection, and 21% of cases had rectal gonorrhoea. MSW cases did not differ from MSM by age, origin or source of infection, but frequencies of prior or concurrent STI were lower. Female cases were younger than male, were mostly foreigners (58%), and 41% were sex workers; concurrent STI (other than HIV) were diagnosed in 30%; 20.4% had symptoms (72.5% and 89.2% in MSM and MSW), and pharyngeal location was present in 30%.HIV co-infection was highest in MSM (20.9%). Co-infection was associated with age > 35 years, low educational level, being Western European or Latin-American, being MSM, having previous or concurrent STI and reporting contact with an HIV-infected partner; it was inversely associated with female sex. CONCLUSION: Differences by sex, transmission route and origin should be considered when implementing care and preventive programmes for gonorrhoea, and MSM are a priority group for intervention, in particular HIV-infected MSM.


Asunto(s)
Gonorrea/diagnóstico , Instituciones de Salud/estadística & datos numéricos , Adulto , Coinfección , Femenino , Gonorrea/transmisión , Infecciones por VIH/complicaciones , Heterosexualidad/estadística & datos numéricos , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores Sexuales , España , Adulto Joven
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