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1.
Psychiatry Res ; 288: 112988, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32387919

RESUMO

Suicidal thoughts and behaviors (STB) include suicidal ideation (SI), suicide attempt (SA) and completed suicide. We aimed to identify recurrence predictors of any type of STB, and separately for SA and SI, and to analyze the time until event. A 108-subject cohort presenting at Emergencies with STB was followed during one year. Recurrence risk factors were investigated by multiple Cox survival regressions. Within one year, 31.5%, 23.1% and 9.3% patients recurred with any STB, SA, and SI respectively. Most recurrences (~70%) occurred within the first 6 months. Seeking emergency psychiatric assistance for problems other than STB during follow-up was a common predictor for recurrence of any STB, and SA and SI specifically. Previous SA history and contact with psychiatry outpatient units during follow-up predicted both STB in general and SA in particular. A specific predictor for SA was hospitalization at index, while SI recurrence was associated to SI at index. These results highlight the importance of early intervention and multidisciplinary follow-up considering concurrent psychosocial or adaptive problems. A careful exploration at Emergencies is needed to target potential predictors.

2.
MEDICC Rev ; 22(1): 17-27, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32327618

RESUMO

INTRODUCTION Human papillomaviruses and Chlamydia tracho-matis are the most frequent causes of sexually transmitted infec-tions. Although the association between some human papillomavirus genotypes and cervical cancer has been demonstrated and Chla-mydia trachomatis infection is the most common cause of female infertility, Cuba has no national baseline studies on the circulation and co-circulation of these agents, the synergistic effect of which may be a risk factor for occurrence and development of precancer-ous cervical lesions. Additionally, few local studies have examined risk factors for infection.OBJECTIVE Determine the frequency of infection by human papil-lomavirus and Chlamydia trachomatis and their association with sociodemographic, clinical and epidemiological variables in women seeking routine Pap smears or other medical services at the primary care level in Cuba.METHODS A cross-sectional study was conducted among 500 wom-en aged 16-67 years (100 from Havana, 200 from Villa Clara and 200 from Holguín Provinces, Cuba), from August through December 2015. Chlamydia trachomatis infection was detected by real-time polymerase chain reaction and 35 genotypes of human papillomavirus by low-density microarray. We then examined the association of infec-tion with sociodemographic, clinical and epidemiological variables.RESULTS Human papillomavirus was detected in 14.8% (74/500) of the women. Of the 29 genotypes identifi ed, 79.7% (59/74) were onco-genic high-risk types. Type 16 was the most frequently identifi ed (23%; 17/74), followed by type 31 (10.8%; 8/74) and then by types 33, 53, 61 and 66 in equal proportions (8.1%; 6/74). Infection frequency was greater in women aged ≤25 years (38.8%; 31/80), students (46.7% 7/15), single women (23.0%; 40/174) and among those who reported having more than 3 sexual partners in the last 2 years (41.5%; 17/41). Differences were found among provinces for circulating genotypes and infection-related variables. Human papillomavirus infection from genotypes 16, 31, 33, 53, 61, 66, 68 and 89 was associated with the 7.9% (30/382) of women who had positive Pap tests. Infection fromChlamydia trachomatis was positive in 1% (5/500) of women, all aged ≤25 years. Coinfection by Chlamydia trachomatis and HPV was found in one woman infected with human papillomavirus genotype 61.CONCLUSIONS Frequency of human papillomavirus is high in the three Cuban provinces studied, with greater frequency of genotype 16 and other oncogenic high-risk types. For both agents, infection is more frequent in young women and adolescents. Positive Pap tests are fre-quently associated with HPV infection. Prevalence fi ndings from this study could be used as a baseline for future research or interventions. KEYWORDS Human papillomavirus, genotypes, Chlamydia tracho-matis, neoplasms, sexually transmitted diseases, cervix Uteri, infec-tion, real-time polymerase chain reaction, women, Cuba.

3.
Liver Int ; 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32329119

RESUMO

BACKGROUND & AIMS: Check point inhibitors (CPI) have improved survival of oncology patients but adverse effects that mimic autoimmune disorders have been reported. Our aim was describe the characteristics of immune-related hepatitis (irH) and prognosis, and compared them to those of patients with autoimmune hepatitis (AIH). METHODS: this a retrospective study including all grade ≥ 3 (severe) irH diagnosed among 414 patients treated with CPI from 2016 to 2018. RESULTS: 28 cases of severe irH were recorded: 10 on anti-CTLA-4 ± anti-PD1/PD-L1 and 18 on anti-PD1/PD-L1. Half were female, age 63 years, median time on CPI 3 cycles. Four (14.3%) presented acute liver injury or failure and 1 (3.6%) died as consequence. 94% presented normal immunoglobulin G (IgG). Six (21.4%) patients were retreated with CPI and none presented relapse or new immune-related adverse events after a median cycles of 11 (range 6-36). Subjects with irH were older and had lower IgG values than a cohort of AIH (N=38). Presentation tended to be more severe in AIH. Twenty-five percent of irH and 84% AIH presented ANAs ≥1:80 (p=0.001). In irH Initial dose of corticosteroids was higher (60 vs 30 mg, p<0.001) but duration shorter (2.3 vs 7 months, p<0.001) and frequently in monotherapy (41.7% vs 91.3%, p<0.001). CONCLUSIONS: immune-related hepatitis can lead to acute liver failure, with absence of increased values of IgG and ANAs. In contrast to autoimmune hepatitis, initial corticosteroids dose were higher, duration shorter with few requiring additional immunosuppression. Retreatment with CPI was not associated with recurrence.

4.
Curr Med Res Opin ; : 1-11, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32267785

RESUMO

Objective: Clinical guidelines for the treatment of septic shock are based on the studies with the best scientific evidence, which are meta-analyses of clinical trials. However, these meta-analyses may have methodological limitations that prevent their conclusions from being extrapolated to routine clinical practice. Therefore, the objective of this study is to determine the quality of these meta-analyses through a systematic review.Methods: In this systematic review, we searched MEDLINE, Scopus and EMBASE from inception to May 2019. We selected meta-analyses from clinical trials that determined the effectiveness of an intervention in reducing the incidence of mortality in patients with septic shock. All items were extracted from the Overview Quality Assessment Questionnaire (OQAQ), which collects information from both systematic reviews and meta-analyses.Results: A total of 34 studies were included. Most elements of the OQAQ were conducted satisfactorily, although 35.3% of meta-analyses did not use a quality assessment of the studies included in other analyses. In 52.9% of meta-analyses, the quality of the studies was high or very high.Conclusions: The methods used to obtain the results should be taken into account when recommending an intervention to treat septic shock if the evidence comes from a meta-analysis of the analyzed characteristics.

5.
Clin Rheumatol ; 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32248433

RESUMO

To evaluate the response to hepatitis B virus (HBV) vaccine in patients on biological therapy. Adults with autoimmune inflammatory diseases on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included. Hepatitis B surface antibody (anti-HBs) was measured by ELISA before and after vaccination. Seroconversion was considered when an anti-HBs titer > 10 mIU/mL was achieved. The effect of treatment on the immunoprotective state was studied. The response was compared with that obtained in patients on synthetic disease modifying anti-rheumatic drugs (DMARDs) and healthy controls. A total of 187 patients on biologicals, 48 on synthetic DMARDs, and 49 on healthy controls were analyzed. More than 80% of patients on biologics responded to the vaccine but required more boosters and second vaccine series. Patients who achieved seroconversion were younger than those who did not (47.10 ± 12.99 vs. 53.18 ± 10.54 years, p = 0.012). Being on etanercept or golimumab was associated with seroconversion, while being on rituximab was not. Seroconversion was achieved in 93.75% of patients on synthetic DMARDs and 97.96% of healthy controls. The seroconversion rate in the biologics group was lower than in the synthetic DMARD group (p = 0.043) and tended to be lower than in the healthy group (p = 0.056). In patients on biological therapy, a high rate of HBV vaccine response can be achieved when a complete vaccination schedule is administered. Vaccination while not on biological agents reduces the requirement for boosters and revaccination.Key points:• Patients on biological therapy can achieve high rates of immune response to HBV vaccine when complete vaccination schedules are administered.• However, to achieve such a high seroconversion rate, more boosters and second vaccination series are required.• This supports the proposal already made to provide HBV vaccination to all patients with an autoimmune inflammatory disease after the diagnosis is made and not when the use of a biological treatment is under consideration.

6.
Med Clin (Barc) ; 2020 Mar 04.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32145988

RESUMO

Fitz-Hugh-Curtis syndrome (FHCS), also known as perihepatitis, is a rare complication of pelvic inflammatory disease. It has a different incidence depending on which diagnostic criteria are used. FHCS consists of inflammation of the hepatic capsule and surrounding peritoneum, without involvement of the hepatic parenchyma, due to intraperitoneal dissemination from a pelvic infection. Clinical manifestations are nonspecific and include a sudden onset of pain and discomfort in the right hypochondrium, commonly confused with other hepatobiliary, gastrointestinal or renal diseases. In recent years, Multidetector Computed Tomography has proven to be a very useful and non-invasive tool, which offers diagnostic confidence within the appropriate clinical setting. Radiological diagnosis of FHCS can avoid unnecessary surgical procedures.

7.
J Viral Hepat ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32106351

RESUMO

Hepatitis E virus (HEV) is the leading cause of acute hepatitis worldwide. The minimum criterion for diagnosis of acute infection is detection of anti-HEV antibodies, although there are scant data on IgM duration. Our aim was to assess the persistence of HEV markers after acute self-limited hepatitis E. HEV serological tests (IgM by Mikrogen and Wantai and HEV-Ag) and HEV RNA were carried out in two cohorts: (a) patients with prior acute hepatitis E (ALT >10 x ULN plus positive IgM ± HEV RNA) currently self-limited and (b) 50 blood donors with positive HEV RNA. Among 25 cases of prior acute hepatitis E, after a median follow-up of 34 months, all presented undetectable HEV RNA. However, anti-HEV IgM remained detectable in 14 (56%) by Mikrogen, 6 (24%) by Wantai and none for HEV-Ag. Anti-HEV IgM tested positive in 80%-100% within the second year and 17%-42% over 3 years later, by Wantai and Mikrogen, respectively. Among HEV RNA-positive donors, 12 (25%) tested positive for either IgM by Mikrogen or Wantai, 9 (18%) for both and 18 (36%) for HEV-Ag. HEV-Ag positivity was more likely as HEV RNA was higher (14% if <2.2 log IU/mL; 64% if RNA ≥ 3.7). Overall, HEV-Ag performed best, with a positive predictive value of 100% and diagnostic accuracy of 57%. Anti-HEV IgM exhibited unexpectedly long persistence after a self-limited acute hepatitis E. HEV-Ag had the best performance and could be especially useful in settings where HEV RNA is not available.

8.
J Sci Food Agric ; 100(7): 3036-3045, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32057099

RESUMO

BACKGROUND: Exhausted sugar beet pulp pellets (ESBPP), a sugar industry by-product generated after sugar extraction in the sugar production process, have been used as a raw material for lactic acid (LA) production via hydrolysis and fermentation by Lactobacillus casei. To design a more cost-effective process, simultaneous saccharification and fermentation (SSF) of ESBPP is proposed in the present study. The effects of pH control, nutrient supplementation and solid addition in fed-batch SSF on lactic acid production were investigated. RESULTS: The highest LA concentration (26.88 g L-1 ) was reached in fed-batch SSF at a solid/liquid loading of 0.2 g mL-1 , with pH control (by adding 30 g L-1 CaCO3 to the medium) and nutrient supplementation (by adding 20 mL of MRS medium per 100 mL of buffer). Under these conditions, a maximum productivity of 0.63 g L-1 h-1 was achieved, which is 2.7 times higher than that attained in the control experiment (SSF inoculated at time 0 h). However, a slightly lower LA yield was obtained, revealing the need of an increasing dose of enzymes at high solid loading SSF. CONCLUSION: An efficient fed-batch SSF strategy with pH control and MRS supplementation is described in the present study, attaining higher LA productivity compared to separate hydrolysis and fermentation and SSF. © 2020 Society of Chemical Industry.

9.
Rev Argent Microbiol ; 52(1): 72-81, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-31926749

RESUMO

Persea americana is a species of great nutritional and economic importance for Mexico, however, like any other agricultural crop, it is affected by pests and diseases that limit its worldwide commercialization. The phytopathogenic fungus Colletotrichum gloeosporioides is the causative agent of anthracnose in avocado and manifests itself in the early stages of fruit development as well as in post-harvest and storage, under conditions of high relative humidity (80%) and at temperatures from 20°C, causing losses economic up to 20% of production. Applying geostatistical methods the present study aims to define the spatial distribution of anthracnose in Hass avocado fruits in four municipalities of the State of Mexico during the period from January to June 2017. The results show that the distribution of anthracnose was adjusted to gaussian and exponential models in most, the infestation maps made through the kriging show more than one center of aggregation of the disease, based on it the infested surface was estimated, finding an infestation of more than 50% in the first samples and up to 98% in the samplings belonging to the month of June in all the areas studied.

10.
Health Expect ; 23(1): 5-18, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31489988

RESUMO

BACKGROUND: Showing how engagement adds value for all stakeholders can be an effective motivator for broader implementation of patient engagement. However, it is unclear what methods can best be used to evaluate patient engagement. This paper is focused on ways to evaluate patient engagement at three decision-making points in the medicines research and development process: research priority setting, clinical trial design and early dialogues with regulators and health technology assessment bodies. OBJECTIVE: Our aim was to review the literature on monitoring and evaluation of patient engagement, with a focus on indicators and methods. SEARCH STRATEGY AND INCLUSION CRITERIA: We undertook a scoping literature review using a systematic search, including academic and grey literature with a focus on evaluation approaches or outcomes associated with patient engagement. No date limits were applied other than a cut-off of publications after July 2018. DATA EXTRACTION AND SYNTHESIS: Data were extracted from 91 publications, coded and thematically analysed. MAIN RESULTS: A total of 18 benefits and 5 costs of patient engagement were identified, mapped with 28 possible indicators for their evaluation. Several quantitative and qualitative methods were found for the evaluation of benefits and costs of patient engagement. DISCUSSION AND CONCLUSIONS: Currently available indicators and methods are of some use in measuring impact but are not sufficient to understand the pathway to impact, nor whether interaction between researchers and patients leads to change. We suggest that the impacts of patient engagement can best be determined not by applying single indicators, but a coherent set of measures.

11.
Neuroepidemiology ; 54(1): 33-44, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31461702

RESUMO

OBJECTIVE: Traumatic brain injury (TBI) is a public health problem worldwide. Information regarding TBI from low- and middle-income countries is scarce. The objectives of this study are to determine the incidence, mortality and geodemographic distribution of TBI in Ecuador. METHODS: A population-based analytical study from 2004 to 2016 was conducted in Ecuador. Men and women with a diagnosis of TBI from all ages (0-110 years) were included. Data was obtained from official hospital-discharges records and retrieved from the National Institute of Statistics and Census (INEC) Database. We analyzed data by region, province and canton with a monthly resolution. The incidence, mortality, case fatality rates and the risk of developing TBI within the population were calculated based on the last 13 years of available data. RESULTS: A total of 124,576 hospital admissions and 5,264 deaths due to TBI were registered in Ecuador from 2004 to 2016. The overall TBI-related hospital admission rate was 70.68 per 100,000. The sex- and age-specific rate was 90.1 per 100,000 for men and 64.1 per 100,000 for women. Mestizos' population has the highest adjusted incidence rate of 195.6 per 100,000, followed by the indigenous with 61.4 per 100,000 and Afro-Americans with 14.2 per 100,000. The overall annual mortality rate during the study ranged from 2.11 to 3.35 per 100,000. Case fatality rates were significantly higher in older populations, becoming fatal in up to 27% of men >90 years/old and in 15% of women older than 90 years/old. CONCLUSION: This is the first recorded epidemiological study of the socio-demographic distribution of TBI in Ecuador to date. The study found that young men were almost 4 times more likely to be hospitalized due to TBI than women of this age. Fatalities due to TBI were less likely to occur among younger age groups, increasing significantly among the elderly population. The national incidence rate of TBI has been decreasing since 2011, which coincides with the introduction of stricter alcohol regulation, suggesting that this measure might have played a role in this reduction.

13.
Sci Rep ; 9(1): 20017, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882712

RESUMO

Delayed enhancement cardiovascular magnetic resonance (MR) is the gold-standard for non-invasive assessment after myocardial infarction (MI). MR microscopy (MRM) provides a level of detail comparable to the macro objective of light microscopy. We used MRM and correlative histopathology to identify infarct and remote tissue in contrast agent-free multi-sequence MRM in swine MI hearts. One control group (n = 3 swine) and two experimental MI groups were formed: 90 min of ischemia followed by 1 week (acute MI = 6 swine) or 1 month (chronic MI = 5 swine) reperfusion. Representative samples of each heart were analysed by contrast agent-free multi-sequence (T1-weighting, T2-weighting, T2*-weighting, T2-mapping, and T2*-mapping). MRM was performed in a 14-Tesla vertical axis imager (Bruker-AVANCE 600 system). Images from MRM and the corresponding histopathological stained samples revealed differences in signal intensities between infarct and remote areas in both MI groups (p-value < 0.001). The multivariable models allowed us to precisely classify regions of interest (acute MI: specificity 92% and sensitivity 80%; chronic MI: specificity 100% and sensitivity 98%). Probabilistic maps based on MRM images clearly delineated the infarcted regions. As a proof of concept, these results illustrate the potential of MRM with correlative histopathology as a platform for exploring novel contrast agent-free MR biomarkers after MI.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31869006

RESUMO

Cervical rib resection through a supraclavicular approach is a safe and feasible treatment for patients suffering from thoracic outlet syndrome caused by the presence of a cervical rib or by an anomalous first rib. This video tutorial illustrates the technical aspects of this procedure.


Assuntos
Costela Cervical/cirurgia , Síndrome do Desfiladeiro Torácico/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
15.
Asclepio ; 71(2): 0-0, jul.-dic. 2019.
Artigo em Espanhol | IBECS-Express | ID: ibc-ET1-5212

RESUMO

En el verano de 1883, el escritor, minero, científico y seguidor del espiritismo Pedro Castera (1846-1906) fue recluido en el Hospital de San Hipólito para hombres dementes de la Ciudad de México. El confinamiento y la situación de aislamiento del también poeta despertó acalorados debates y disputas sobre su condición mental. Los motivos de su internamiento y las conjeturas acerca de la psicopatología que lo aquejaba fueron cruciales dentro de la narrativa de este caso, en el que convergieron intrigas políticas, sospechas familiares, controversias médicas y convenciones literarias. El objetivo del presente trabajo es analizar las valoraciones médicas alrededor de la reclusión, permanencia y salida de Pedro Castera del nosocomio, con el fin de reflexionar, asimismo, en torno a la resignificación de la figura del loco-literario, a partir de la emergencia del discurso de la medicina mental en el contexto de la modernidad mexicana en el último tercio del siglo XIX


In the summer of 1883, the writer, miner, scientist and follower of spiritism Pedro Castera (1846-1906) was detained at the Hospital de San Hipólito for demented men in Mexico City. The confinement and isolation of the also poet aroused heated debates and disputes surrounding his mental condition. The reasons for his internment and the conjectures about the psychopathology that afflicted him were crucial within the narrative of a case in which political intrigues, family suspicions, medical controversies and literary conventions converged. The aim of the present work is to analyze the medical valuations around the confinement, permanence and exit of Pedro Castera in and from the hospital, as well as to reflect on the resignification of the figure of the literary-madman from the emergence of the discourse of mental medicine in the context of Porfirian modernity

16.
PLoS One ; 14(11): e0224568, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31689315

RESUMO

AIM: Liver transplantation is the only curative strategy for final stage liver diseases. Despite the great advances achieved during the last 20 years, the recipient immune response after transplantation is not entirely controlled. This results in high rates of acute cell rejection and, approximately, 10% of early mortality. Therapeutic treatment could be improved by efficiently transfecting genes that encode natural immunosuppressant proteins, employing safe procedures that could be transferred to clinical setting. In this sense, interleukin 10 plays a central role in immune tolerance response by acting at different levels. METHODS: hIL10 gene was hydrofected by retrograde hydrodynamic injection in pig liver with complete vascular exclusion mediated by an 'in vivo' surgical procedure. Levels of IL10 DNA, RNA and protein were determined within liver tissue 1 and 10 days after the injection and, more frequently, also the interleukin-10 protein in peripheral blood. RESULTS: The procedure was safe for the animals and neither hemodynamic parameters nor liver function determinations showed relevant alterations. The hIL10 hydrofection in watertight liver mediated efficient gene transfer and this was transcribed and translated to protein, achieving up to 110 pg/ml of IL10 in peripheral blood. This value is close to that considered able to reduce the activity of TNFα by half (IL10 IC50 for TNFα = 124 pg/ml). CONCLUSIONS: Results of this work suggest that IL10 liver hydrofection with vascular exclusion in vivo is a safe and transferable procedure that mediates plasma protein levels with potential clinical interest in immune modulation after transplantation.

17.
Med. clín (Ed. impr.) ; 153(10): 380-386, nov. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-186936

RESUMO

Background and objectives: Influenza vaccine is recommended for patients with autoimmune inflammatory rheumatic diseases who receive biological therapy. To evaluate if biological therapy impairs immunization after seasonal influenza vaccine. Material and methods: Patients with inflammatory arthopathies, psoriasis, inflammatory bowel disease or connective tissue diseases who were receiving or were going to initiate biological therapy were included and vaccinated during 2014-2015 influenza season. ELISA was used to measure influenza antigen A and B antibodies, before and after vaccination. Demographic parameters, diagnosis and kind of treatment were recorded and their influence on the final serological status against influenza was studied. Results: 253 subjects were analyzed. After vaccination, 77% of participants presented detectable antibodies against antigen A and 50.6% of them had detectable antibodies against antigen B. Final seropositivity rate against antigen B antibodies increased from baseline (50.6% vs 43.5%, p<0.001). Anti-TNF drugs were associated with better response and rituximab with the worst (79.2% vs 55.0% for final seropositivity against antigen A, p=0.020). Vaccine response in the rituximab group tended to improve when the interval between the drug administration and the vaccination was at least 12 weeks (seropositivity rate 80.0% in those with the longer interval vs 25.0% in the other group, p=0.054). Conclusions: Among the patients on biological therapy vaccinated against influenza, anti-TNF therapy was identified as a predictive factor of final seropositivity. Rituximab presented a lower rate of final seropositivity, which could be increased with an accurate administration schedule


Antecedentes y objetivos: La vacunación antigripal está recomendada en pacientes con enfermedades autoinmunes sistémicas que reciben tratamientos biológicos. Evaluar si la terapia biológica puede perjudicar la inmunización después de la administración de la vacuna contra la gripe estacional. Material y métodos: Los pacientes con artropatías inflamatorias, psoriasis, enfermedad inflamatoria intestinal o enfermedades del tejido conectivo, que estaban en tratamiento o que iban a iniciar tratamiento con terapia biológica, fueron incluidos en el estudio y vacunados durante la temporada de influenza 2014-2015. Se utilizó ELISA para medir los anticuerpos contra los antígenosA y B de la gripe, antes y después de la vacunación. Se registraron los datos demográficos, diagnósticos y el tipo de tratamiento y se estudió su influencia sobre el estado serológico final contra la influenza. Resultados: Se analizaron 253 sujetos. Después de la vacunación, el 77% de los participantes presentaron anticuerpos detectables contra el antígeno A y el 50,6% de ellos tenían anticuerpos detectables contra el antígeno B. La tasa de seropositividad final de anticuerpos contra el antígeno B aumentó desde los valores basales (50,6% frente a 43,5%, p<0,001). Los fármacos anti-TNF se asociaron con la mejor respuesta y rituximab con la peor (79,2% vs. 55,0% para la seropositividad final contra el antígeno A, p=0,020). La respuesta a la vacuna en el grupo de rituximab tuvo tendencia a mejorar cuando el intervalo entre la administración del fármaco y la vacunación fue por lo menos de 12 semanas (tasa de seropositividad del 80,0% en aquellos con el intervalo más largo frente al 25% en el otro grupo, p=0.054). Conclusiones: Entre los pacientes en terapia biológica vacunados contra la influenza, la terapia anti-TNF se identificó como un factor predictivo de la seropositividad final. Rituximab presentó una tasa más baja de seropositividad final, que podría aumentarse con un programa de administración preciso


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Vacinas contra Influenza/uso terapêutico , Doenças Autoimunes/terapia , Vacinação/métodos , Vacinas contra Influenza/imunologia , Doenças Autoimunes/imunologia , Ensaio de Imunoadsorção Enzimática , Rituximab/administração & dosagem , Análise de Regressão
18.
J Am Coll Cardiol ; 74(15): 1910-1923, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31601371

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with important vascular and hemostatic alterations that should be taken into account during diagnosis and treatment. OBJECTIVES: This study evaluates whether anticoagulation with dabigatran, a clinically approved oral direct thrombin inhibitor with a low risk of intracerebral hemorrhage, ameliorates AD pathogenesis in a transgenic mouse model of AD. METHODS: TgCRND8 AD mice and their wild-type littermates were treated for 1 year with dabigatran etexilate or placebo. Cognition was evaluated using the Barnes maze, and cerebral perfusion was examined by arterial spin labeling. At the molecular level, Western blot and histochemical analyses were performed to analyze fibrin content, amyloid burden, neuroinflammatory activity, and blood-brain barrier (BBB) integrity. RESULTS: Anticoagulation with dabigatran prevented memory decline, cerebral hypoperfusion, and toxic fibrin deposition in the AD mouse brain. In addition, long-term dabigatran treatment significantly reduced the extent of amyloid plaques, oligomers, phagocytic microglia, and infiltrated T cells by 23.7%, 51.8%, 31.3%, and 32.2%, respectively. Dabigatran anticoagulation also prevented AD-related astrogliosis and pericyte alterations, and maintained expression of the water channel aquaporin-4 at astrocytic perivascular endfeet of the BBB. CONCLUSIONS: Long-term anticoagulation with dabigatran inhibited thrombin and the formation of occlusive thrombi in AD; preserved cognition, cerebral perfusion, and BBB function; and ameliorated neuroinflammation and amyloid deposition in AD mice. Our results open a field for future investigation on whether the use of direct oral anticoagulants might be of therapeutic value in AD.

19.
RMD Open ; 5(2): e001018, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565246

RESUMO

Objective: To evaluate whether immunological response to influenza vaccination is impaired in patients who are receiving secukinumab. Patients and methods: Subjects suffering from psoriatic arthritis or ankylosing spondylitis who were receiving treatment with secukinumab and healthy volunteers were included.All participants received seasonal inactivated trivalent influenza vaccine recommended by the WHO in the 2017-2018 northern hemisphere influenza season, which contained an A/Michigan/45/2015 (H1N1)pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus and a B/Brisbane/60/2008-like virus.Haemagglutination inhibition was used to evaluate basal antibody (Ab) titres against the three influenza vaccine virus strains just before vaccination and at least 4 weeks after the vaccine administration. Response to vaccine was considered as >4-fold increases in Ab titre. Results: Thirty subjects, 17 patients and 13 healthy controls, with a follow-up duration of 33±8 days, were analysed. There were no demographic differences between groups. Patients and controls achieved a median of 4.6-fold and 4.0-fold increases, respectively, for anti H1N1 and almost 4.0 (3.7) for patients and 5.3 for controls for anti-B Ab. Both groups presented a poor response against H3N2, with <1.5-fold increase. Seroconversion rates were similar in both groups. Secukinumab did not influence the response to the influenza vaccine (relative risk: 1.09 (95% CI 0.58 to 2.07) for H1N1, RR: 1.53 (95% CI 0.15 to 15.0) for H3N2 and RR: 0.72 (95% CI 0.32 to 1.83) for B strain). Conclusion: In our study, secukinumab has no effect on the immunogenic response to the influenza vaccine.

20.
mSphere ; 4(5)2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484739

RESUMO

Urgency urinary incontinence (UUI) and overactive bladder (OAB) can both potentially be influenced by commensal and urinary tract infection-associated bacteria. The sensing of bladder filling involves interplay between various components of the nervous system, eventually resulting in contraction of the detrusor muscle during micturition. This study models host responses to various urogenital bacteria, first by using urothelial bladder cell lines and then with myofibroblast contraction assays. To measure responses, we examined Ca2+ influx, gene expression, and alpha smooth muscle actin deposition assays. Organisms such as Escherichia coli and Gardnerella vaginalis were found to strongly induce Ca2+ influx and contraction, whereas Lactobacillus crispatus and L. gasseri did not induce this response. Additionally, supernatants from lactobacilli impeded Ca2+ influx and contraction induced by uropathogens. Upon further investigation of factors associated with purinergic signaling pathways, the Ca2+ influx and contraction of cells correlated with the amount of extracellular ATP produced by E. coli Certain lactobacilli appear to mitigate this response by utilizing extracellular ATP or producing inhibitory compounds that may act as a receptor agonist or Ca2+ channel blocker. These findings suggest that members of the urinary microbiota may be influencing UUI or OAB.IMPORTANCE The ability of uropathogenic bacteria to release excitatory compounds, such as ATP, may act as a virulence factor to stimulate signaling pathways that could have profound effects on the urothelium, perhaps extending to the vagina. This may be countered by the ability of certain commensal urinary microbiota constituents, such as lactobacilli. Further understanding of these interactions is important for the treatment and prevention of UUI and OAB. The clinical implications may require a more targeted approach to enhance the commensal bacteria and reduce ATP release by pathogens.


Assuntos
Trifosfato de Adenosina/metabolismo , Bactérias/metabolismo , Cálcio/metabolismo , Miofibroblastos/citologia , Bexiga Urinária/microbiologia , Actinas/fisiologia , Bactérias/patogenicidade , Linhagem Celular , Colágeno/fisiologia , Humanos , Lactobacillales , Microbiota , Contração Muscular , Miofibroblastos/microbiologia , Simbiose , Bexiga Urinária/fisiologia , Urotélio/citologia
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