Primer consenso cubano sobre el uso de terapia convencional y biológica en pacientes con artritis reumatoide / First Cuban consensus on the use of conventional and biological therapy in patients with rheumatoid arthritis

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Introduction: The development of recommendations for the treatment of rheumatoid arthritis (RA) in the Cuban context may be one of the ways to achieve better control of this disease. Objective: To reach a consensus and update relevant aspects of conventional and biological RA modifier therapy in Cuba. Methods: 18 specialists from 8 Cuban provinces, experts in RA care, were summoned, according to the years of dedication to the specialty, the conferences on this topic and their publications. The first meeting took place in March 2016 in the provincial hospital of Villa Clara, Cuba, with the participation of all the experts. A review of the literature on conventional and biological therapy previously collected by the participants was developed, and two teams were formed: the first would address everything related to conventional therapy in RA (HRCT) and the other, biological therapy in RA (TBAR). Three questionnaires related to the use of corticosteroids, HRCT and TBAR, were prepared, answered by the participants via email. In a second meeting, held in October 2016 in Havana, the analysis of all the responses provided was carried out. Questions with a response of 90% or more votes were considered as recommendations. Results: The questionnaires were answered by 95% of the participants. 9 recommendations and 1 algorithm were established. The recommendations are as follows: methotrexate is the drug of choice in the treatment of RA after diagnosis; The administration of another conventional drug (DMARDc) (azathioprine, salazosulfapyridine, antimalarials and leflunomide) is recommended in patients with a diagnosis of active RA in whom methotrexate is contraindicated or there is a failure in response - consider the administration of low doses of prednisone or equivalent (<7.5 mg/d) associated with DMARDc in patients with active moderate to severe RA, for the shortest possible time; perform serological control including tests for hepatitis B and C viruses and screening for HIV in all patients diagnosed with RA before starting treatment with DMARDc and biologics; in patients in remission or, at least, with a DAS-28 below 3.2, consideration should be given to withdrawing one of the DMARDs or reducing, to the minimum possible expression, the dose of both disease modifiers; if methotrexate fails, tocilizumab in combination with methotrexate or as monotherapy will be indicated. Conclusions: Aspects related to conventional therapy with methotrexate, azathioprine, salazosulfapyridine, antimalarials and leflunomide were agreed. The value of early diagnosis and immediate initiation of DMARDc therapy and the use of glucocorticoids was analyzed. Treatment with tocilizumab, the only biological available in Cuba against RA, will be administered when there is a failure in the response to conventional therapy and combinations between these drugs. It is recommended to hold educational conferences through the mass media aimed at patientshttp(AU)

Aberrantly low STAT3 and STAT5 responses are associated with poor outcome and an inflammatory gene expression signature in pediatric acute myeloid leukemia.

The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low inducible STAT3 activity was independently associated with inferior event-free survival in multivariate analyses. For inducible STAT5 activity, those with the lowest and highest responses had inferior event-free survival, compared to patients with intermediate STAT5 responses. Using existing RNA-sequencing data, we compared gene expression profiles for patients with low inducible STAT3/5 activation with those for patients with higher inducible STAT3/5 signaling. Genes encoding hematopoietic factors and mitochondrial respiratory chain subunits were overexpressed in the low STAT3/5 response groups, implicating inflammatory and metabolic pathways as potential mechanisms of chemotherapy resistance. We validated the prognostic relevance of individual genes from the low STAT3/5 response signature in a large independent cohort of pediatric AML patients. These findings provide novel insights into interactions between AML cells and the microenvironment that are associated with treatment failure and could be targeted for therapeutic interventions.

Mortality risk among women exposed to violence in Brazil: a population-based exploratory analysis.

OBJECTIVES: The objective of this study was to estimate mortality risk among women exposed to violence in Brazil using population-based data. STUDY DESIGN: This study used a linked database containing nearly 800,000 violence (against women) notifications and 16,500 associated deaths over the period 2011-2016. METHODS: Aggregate age-standardized population-based rates of mortality were built to estimate risk ratios (RRs) at the national and state level, and for different forms of violence and causes of death, as well as type of offender involved, and across various characteristics of the women. RRs compared the rate of mortality among women exposed to violence with that in the general population of women - excess mortality due to violence was also derived from this comparison. The analysis was divided into two time periods (2011-13 and 2014-16). RESULTS: During 2014-16, women exposed to violence had an estimated mortality risk that was 8.3 [95% confidence interval (CI): 8.2-8.5] times higher than that of the general woman population, and an estimated 100 women died on a weekly basis as a direct or indirect consequence of exposure to violence. Higher (all-cause) mortality risk was associated with physical violence and violence that involved repetition and that was self-inflicted. The risk of mortality increased when the cause of death involved external causes (RR: 51.2, 95% CI: 49.6-52.8). When death was attributable to (i) non-communicable diseases and (ii) communicable, maternal, neonatal, and nutritional diseases, the risk was 5.4 [95% CI: 5.3-5.6] and 6.7 [95% CI: 6.1-7.2] times, respectively. Women at greatest (all-cause) mortality risk include white and multiracial (parda) and single women in the age group 10-29 years, who live in the northeast part of the country. When the offender was a partner/ex., women aged 10-19 years showed the greatest (all-cause) mortality risk at 16.9 [95% CI: 13.9-19.8] times. Higher risk was also observed within the age group 30-59 years when death was attributable to external causes (RR: 74.6, 95% CI: 71.3-77.9). For younger women and girls, there was a clear gradient in (all-cause) mortality risk, with those living in the poorest municipalities at greater risk. Age-specific mortality risk also showed significant variation within and across states. CONCLUSIONS: This analysis suggests that most women exposed to violence will likely experience an increased risk of mortality, regardless of her place of residence, age group, racial/ethnic background, marital status situation, and socio-economic status. The estimated RRs are only an approximation given the design of this analysis and should be interpreted with caution.

Duplicates and misclassification of tuberculosis notification records in Brazil, 2001-2007.

OBJECTIVE: To evaluate the change in tuberculosis (TB) notification rates due to the removal of unwanted duplicate records from the Brazilian notification system (2001-2007, data extracted in October 2008), and therefore extending the period of investigation of the previous study using the same methodology (2000-2004, data extracted in February 2006). METHODS: Repeat records were identified using a probabilistic record linkage, classified into six mutually exclusive categories, and then kept, combined or removed from the database. RESULTS: In the TB database, 22.7% of all records belonged to patients with multiple records. When we excluded the first record of every patient in this group, 43.7% were classified as transfers, 29% as returns after default, 16.3% as relapses and 6.6% as true duplicates, while 2.9% were inconclusive and 1.5% had missing data. Removal of unwanted duplicate records reduced the notification rates of new cases by 4% to 6.3%, and increased the proportion cured by 3.4% to 4.9%. DISCUSSION: Linkage of records within the TB notification database and the implementation of procedures to distinguish between new and retreatment or transfer-in records yielded better data. Recommendations are provided on how to prevent duplicates and misclassifications in national TB databases.

Isolated tuberculous hepatic abscess.

Tuberculous hepatic abscess occurs rarely, most of these being associated with tuberculosis at other sites. Only 11 reports of isolated tuberculous hepatic abscess have been made in the English literature. A further case of isolated tuberculous hepatic abscess is reported with particular emphasis on the difficulty that may be encountered in reaching the correct diagnosis.

Cuerpos extranos en la via aerea inferior. / Foreign bodies in the lower airway

El material presentado esta constituido por 69 pacientes, observados con cuerpos extranos aspirados en las vias aereas que se analizan de acuerdo a: edad: 76,8% menores de 4 anos - sexo: 66,0% varones- naturaleza: 90,7% radiolucidos - Ubicacion: 23,4% laringea, l5,9% traqueal, 6l,9% bronquial. Desde el punto de vista clinico, antecedentes, sintomas y signos fueron insuficientes para precisar la presencia y localizacion del cuerpo extrano. Los hallazgos radiologicos y adecuada interpretacion de signos indirectos, constituyeron un singular apoyo para el diagnostico. La endoscopia fue el principal procedimiento de extracccion, (97%). El 7,2% de los pacientes eliminaron en forma espontanea el material aspirado. La letalidad alcanzo a un 4,5%. Se insiste la necesidad de un alto indice de sospecha de este problema, frente a trastornos respiratorios de iniciacion brusca y en las complicaciones inmediatas, mediatas y a largo plazo que originan los cuerpos extranos en la via aerea. Se destaca las situaciones clinicas provocadas por cuerpos extranos abandonados, como asimismo las dificultades para el diagnostico que ofrecen los cuerpos extranos plasticos por el caracter no irritativo, su pequeno tamano y por ser radiolucidos