Factors of the epidemiological triad that influence the persistence of human papilloma virus infection in women with systemic lupus erythematosus.

We studied the epidemiologic triad-related factors influencing human papilloma virus (HPV) persistence in Mexican women with systemic lupus erythematosus (SLE). Patients aged ≥18 years with SLE (American College of Rheumatology criteria), with and without HPV persistence, were selected. Groups were analyzed by (1) host: clinical disease characteristics; (2) agent: (I) infectious (prevalence, incidence, HPV genotype and co-infections (≥2 HPV genotypes or mycoplasmas)), (II) chemical (contraceptives and immunosuppressive drugs) and (III) physical (vitamin D deficiency) and (3) environment. A total of 121 SLE patients were selected over a two-year period. (1) Host: mean age 45.8 years and disease duration 12.7 years. (2) Agent: (I) infectious. HPV infection prevalence in the second sample was 26.4%, high-risk HPV genotypes 21.5% and co-infections 7.4%. HPV infection incidence was 13.2%, persistence 13.2% and clearance 15.7%. (II) Chemical: use of oral hormonal contraceptives 5% and immunosuppressive treatment 97.5%. (III) Physical: Vitamin D levels were similar in both groups. (3) Environment: (I) natural. A total of 60.6% of patients were residents of Puebla City. (II) Social: The mean education level was 10.9. Poverty levels were: III degree 52.4%, IV degree 28% and II degree 17%. (III) Cultural behavioral: Onset of sexual life was 20.5 years, 10% had ≥3 sexual partners and 51.2% were postmenopausal. In conclusion, no factor of the epidemiologic triad was associated with HPV infection prevalence.

A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. METHODS: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. RESULTS: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. CONCLUSIONS: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.

Why does measles persist in Europe?

Several reasons may explain why measles was not eliminated by 2015 and continues to persist in Europe, including low measles vaccination coverage, low anti-measles herd immunity levels, and the mobility of individuals with measles across Europe. The study assessed the mean measles vaccination coverage in the European Union and the WHO European region with one and two doses of measles vaccine from 1980 to 2015, and the prevalence of vaccine-induced protected individuals and anti-measles herd immunity levels in the WHO European region during 2000-2015. The study found that measles vaccination coverage with two doses of vaccine was <90% in the European Union and the WHO European region from 1995 to 2015. In the WHO European region, the two-dose measles vaccination coverage during the 2000-2015 period was <95% in 41 countries (79%), and the prevalence of vaccine-induced protected individuals in the target vaccination population was lower than the herd immunity threshold of 94.4% in 33 countries (63%). The additional vaccination coverage required to establish herd immunity in these countries ranged from 0.2% to 18%. Two of the factors explaining measles persistence in Europe in 2015 were the two-dose measles vaccination coverage <95% and the prevalence of individuals with vaccine-induced protection of <94.4% in most countries of the WHO European region during the 2000-2015 period. Screening and vaccination programs should be developed to detect and immunize susceptible individuals in areas and population groups without anti-measles herd immunity in all European countries.

Mycosis Fungoides: Experience in a Pediatric Hospital. / Micosis fungoide. Experiencia en un hospital pediátrico.

Mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, is unusual in children. OBJECTIVES: We aimed to describe the epidemiologic, clinical, histopathologic, and immunophenotypic characteristics of MF as well as treatments and course of disease in a pediatric case series. MATERIAL AND METHOD: Data for all patients admitted to our pediatric hospital (Hospital Dr. J. P. Garrahan) in Argentina with a clinical and histopathologic diagnosis of MF between August 1988 and July 2014 were included. RESULTS: A total of 14 patients were diagnosed with MF. The ratio of boys to girls was 1:1.33. The mean age at diagnosis was 11.23 years (range, 8-15 years). The mean time between onset and diagnosis was 3.5 years (range, 4 months-7 years). All patients had hypopigmented MF and 42% also presented the features of classic MF. Seven (50%) had the CD8+ immunophenotype exclusively. Seventy-eight percent were in stage IB at presentation. Phototherapy was the treatment of choice. Four patients relapsed at least once and skin lesions progressed in 3 patients. All patients improved. CONCLUSIONS: MF is unusual in children. The hypopigmented form is the most common. Diagnosis is delayed because the condition is similar to other hypopigmented diseases seen more often in childhood. Although prognosis is good, the rate of recurrence is high, so long-term follow-up is necessary.

Carbon and Nitrogen Sources Influence Tricalcium Phosphate Solubilization and Extracellular Phosphatase Activity by Talaromyces flavus.

The aim of this work was to study phosphate (P) solubilization (and the processes involved in this event) by Talaromyces flavus (BAFC 3125) as a function of carbon and/or nitrogen sources. P solubilization was evaluated in NBRIP media supplemented with different carbon (glucose, sorbitol, sucrose, and fructose) and nitrogen (L-asparagine, urea, ammonium sulfate (AS), and ammonium nitrate (AN) combinations. The highest P solubilization was related to the highest organic acid production (especially gluconic acid) and pH drop for those treatments where glucose was present. Also P solubilization was higher when an inorganic nitrogen source was supplemented to the media when compared to an organic one. Although not being present an organic P source, phosphatase activity was observed. This shows that P mineralization and P solubilization can occur simultaneously, and that P mineralization is not induced by the enzyme substrate. The combination that showed highest P solubilization was for AN-glucose. The highest acid phosphatase activity was for AS-fructose, while for alkaline phosphatase were for AS-fructose and AN-fructose. Acid phosphatase activity was higher than alkaline. P solubilization and phosphatase activity (acid and alkaline) were influenced by the different carbon-nitrogen combinations. A better understanding of phosphate-solubilizing fungi could bring a better use of soil P.

Antibacterial activity and mode of action of a commercial citrus fruit extract.

AIMS: This study addresses the antibacterial activity and mechanism of action of BIOLL(+®), a commercial extract obtained from citrus fruits. METHODS AND RESULTS: Strong activities with minimum inhibitory concentrations (MIC) ranging from 10 ppm (for some Brachyspira hyodysenteriae strains) to 80 ppm (for various Salmonella enterica and Escherichia coli strains) were observed. Membrane integrity tests and Fourier transform infrared (FT-IR) spectroscopic analyses were performed to shed light on the effects caused on molecular structure and composition. Physical effects, with formation of pores and leakage of intracellular components, and chemical effects, which were dependent on the bacterial species, were evident on cellular envelopes. Whereas for S. enterica and E. coli, changes were focused on the carboxylic group of membrane fatty acids, for B. hyodysenteriae, the main effects were found in polysaccharides and carbohydrates of the cell wall. CONCLUSIONS: The great antibacterial activity shown by BIOLL(+®) and its proposed dual physico-chemical mode of action, with species-specific cellular targets, show its attractiveness as an alternative to antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Antibiotic resistance is becoming a serious problem. Our study characterizes a novel antimicrobial extract, which could represent an alternative to antibiotics for treatment or prevention of bacterial infectious diseases.

[Efficacy, effectiveness and safety of the adjuvanted influenza vaccine in the population aged 65 or over]. / Eficacia, efectividad y seguridad de la vacuna antigripal adyuvada en población de 65 o más años de edad.

Most of the complications and deaths related to seasonal flu occur in the elderly population (≥65 years) with comorbidities, and the influenza vaccine is the most effective way to prevent them. Immunization is less effective in older adults due to immunosenescence. MF59-adjuvanted vaccines, designed to improve the magnitude, persistence and amplitude of the immune response in elderly people, have been used in clinical practice since 1997 in their trivalent formulation and, since 2020, in their tetravalent formulation. Data from various studies show that these vaccines are not only safe for all age groups, with a reactogenicity profile similar to that of the conventional vaccine, but also that they are especially effective in boosting the immune response in the population aged 65 or over by increasing antibody titers after vaccination and significantly reducing the risk of hospital admission. Adjuvanted vaccines have been shown to provide cross-protection against heterologous strains and to be as effective as the high-dose vaccine in the population aged 65 or over. In this review, the scientific evidence on the efficacy and effectiveness of the MF59-adjuvanted vaccine in real clinical practice in people ≥65 years of age is analyzed through a narrative and descriptive review of the literature with data from clinical trials, observational studies and systematic reviews or meta-analysis.

First Reported Case of Malignant Ectomesenchymoma with p.Leu122Arg Mutation in MYOD1 Gene: Extensive Intra- and Extracranial Tumor in a 15-Year-Old Female.

BACKGROUND: Ectomesenchymomas (EMs) are extremely rare neoplasms composed of malignant mesenchymal components and neuroectodermal derivatives. They are described in a wide variety of locations, with the head and neck region being one of the most frequently involved areas. EMs are usually managed as high-risk rhabdomyosarcomas and have similar outcomes. METHODS: We present the case of a 15-year-old female with an EM that arose in the parapharyngeal space and extended into the intracranial space. RESULTS: Histologically, the tumor presented an embryonal rhabdomyosarcomatous mesenchymal component and the neuroectodermal component was constituted by isolated ganglion cells. Next-generation sequencing (NGS) revealed a p.Leu122Arg (c.365 T > G) mutation in the MYOD1 gene, a p.Ala34Gly mutation in the CDKN2A gene, and CDK4 gene amplification. The patient was treated with chemotherapy. She died 17 months after the debut of symptoms. CONCLUSION(S): To our knowledge, this is the first reported case in English literature of an EM with this MYOD1 mutation. We suggest combining PI3K/ATK pathway inhibitors in these cases. NGS should be performed in EMs cases to detect mutations with potential treatment options.

Optimization of municipal sludge and grease co-digestion using disintegration technologies.

Many drivers tend to foster the development of renewable energy production in wastewater treatment plants as many expectations rely upon energy recovery from sewage sludge, for example through biogas use. This paper is focused on the assessment of grease waste (GW) as an adequate substrate for co-digestion with municipal sludge, as it has a methane potential of 479-710 LCH(4)/kg VS, as well as the evaluation of disintegration technologies as a method to optimize the co-digestion process. With this objective three different pre-treatments have been selected for evaluation: thermal hydrolysis, ultrasound and enzymatic treatment. Results have shown that co-digestion processes without pre-treatment had a maximum increment of 128% of the volumetric methane productivity when GW addition was 23% inlet (at 20 days of HRT and with an OLR of 3.0 kg COD/m(3)d), compared with conventional digestion of sewage sludge alone. Concerning the application of the selected disintegration technologies, all pre-treatments showed improvements in terms of methane yield (51.8, 89.5 and 57.6% more for thermal hydrolysis, ultrasound and enzymatic treatment, respectively, compared with non-pretreated wastes), thermal hydrolysis of GW and secondary sludge being the best configuration as it improved the solubilization of the organic matter and the hydrodynamic characteristics of digestates.

Leiomyomatosis peritonealis disseminata with malignant degeneration. A case report.

Leiomyomatosis peritonealis disseminata (LPD) is an uncommon condition characterized by multiple nodules of smooth muscle within the peritoneal cavity. It usually occurs during reproductive age, and is especially associated to exogenous and endogenous exposure to female gonadal steroids. A limited number of cases of malignant transformation have been reported in the literature. We report a case of leiomyomatosis peritoneais disseminata with sarcomatous degeneration in a 37-year-old nulligravid patient with no exposure to exogenous estrogen or progesterone, revealed by increased abdominal perimeter. The imaging techniques showed occupation of the entire peritoneal cavity by bulky solid masses. The patient underwent a total hysterectomy with bilateral salpingo-oophorectomy and tumoral mass resection. The histopathologic diagnosis was leiomiomatosis peritonealis disseminata with leiomyosarcomatous degeneration. The patient was given systemic chemotherapy with tumoral progression, and died 24 months after the initial diagnosis.

Usefulness of Video-EEG monitoring in patients with drug-resistant epilepsy.

OBJECTIVE: To evaluate the characteristics of patients on whom long-term Video-EEG monitoring is performed in a specialist centre and to assess its suitability to study refractory epilepsy patients. METHODS: A prospective analysis and study of Video-EEG monitoring was performed in a series of 100 refractory epilepsy patients from a single centre. The analysis included demographic data, the time until the first seizure, the methods used to provoke seizures, and the outcome (usefulness, change in the management, pharmacological and surgical improvement). A subgroup analysis based on diagnosis was performed. RESULTS: The study was performed mainly on young people (mean 34.4 years) and the first seizure appeared in a mean of 30hours, requiring most of the patients to withdraw the medication. Nevertheless, there were no cases of status epilepticus. The usefulness of the test was high in all the groups. The management was changed in 65% of the patients with pharmacological and surgical improvement. CONCLUSION: Long-term Video-EEG monitoring is a suitable test to study refractory epilepsy patients. The main problem in our country is accesibility.

Genetic predisposition to fetal and neonatal cancer.

BACKGROUND: Neonatal tumors represent an extremely rare and heterogeneous disease with an unknown etiology. Due to its early onset, it has been proposed that genetic factors could play a critical role; however, germline genetic analysis is not usually performed in neonatal cancer patients PATIENTS AND METHODS: To improve the identification of cancer genetic predisposition syndromes, we retrospectively review clinical characteristics in 45 patients with confirmed tumor diagnosis before 28 days of age, and we carried out germline genetic analysis in 20 patients using next-generation sequencing and directed sequencing. RESULTS: The genetic studies did not find any germline mutation except patients diagnosed with bilateral retinoblastoma who harbored RB1 germline mutations. CONCLUSIONS: Our results suggest that genetic factors have almost no higher impact in most neonatal tumors. However, since the heterogeneity of the tumors and the small sample size analyzed, we recommend complementary and centralized germline studies to discard the early onset as an additional criterion to take into account to improve the identification of cancer genetic predisposition syndromes in neonates.

GEIS-SEHOP clinical practice guidelines for the treatment of rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma (STS) in children and adolescents. In Spain the annual incidence is 4.4 cases per million children < 14 years. It is an uncommon neoplasm in adults, but 40% of RMS are diagnosed in patients over 20 years of age, representing 1% of all STS in this age group. RMS can appear anywhere in the body, with some sites more frequently affected including head and neck, genitourinary system and limbs. Assessment of a patient with suspicion of RMS includes imaging studies (MRI, CT, PET-CT) and biopsy. All patients with RMS should receive chemotherapy, either at diagnosis in advanced or metastatic stages, or after initial resection in early local stages. Local control includes surgery and/or radiotherapy depending on site, stage, histology and response to chemotherapy. This guide provides recommendations for diagnosis, staging and treatment of this neoplasm.

Gallbladder disease and pancreatic cancer risk: a multicentric case-control European study.

BACKGROUND AND AIMS: The overall evidence on the association between gallbladder conditions (GBC: gallstones and cholecystectomy) and pancreatic cancer (PC) is inconsistent. To our knowledge, no previous investigations considered the role of tumour characteristics on this association. Thus, we aimed to assess the association between self-reported GBC and PC risk, by focussing on timing to PC diagnosis and tumour features (stage, location, and resection). METHODS: Data derived from a European case-control study conducted between 2009 and 2014 including 1431 PC cases and 1090 controls. We used unconditional logistic regression models to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) adjusted for recognized confounders. RESULTS: Overall, 298 (20.8%) cases and 127 (11.6%) controls reported to have had GBC, corresponding to an OR of 1.70 (95% CI 1.33-2.16). The ORs were 4.84 (95% CI 2.96-7.89) for GBC diagnosed <3 years before PC and 1.06 (95% CI 0.79-1.41) for ≥3 years. The risk was slightly higher for stage I/II (OR = 1.71, 95% CI 1.15-2.55) vs. stage III/IV tumours (OR = 1.23, 95% CI 0.87-1.76); for tumours sited in the head of the pancreas (OR = 1.59, 95% CI 1.13-2.24) vs. tumours located at the body/tail (OR = 1.02, 95% CI 0.62-1.68); and for tumours surgically resected (OR = 1.69, 95% CI 1.14-2.51) vs. non-resected tumours (OR = 1.25, 95% CI 0.88-1.78). The corresponding ORs for GBC diagnosed ≥3 years prior PC were close to unity. CONCLUSION: Our study supports the association between GBC and PC. Given the time-risk pattern observed, however, this relationship may be non-causal and, partly or largely, due to diagnostic attention and/or reverse causation.

Characterization and epidemiological relationships of Spanish Brachyspira hyodysenteriae field isolates.

This research aimed to describe the genetic and phenotypic diversity of 74 Spanish Brachyspira hyodysenteriae field isolates, to establish epidemiological relationships between the isolates and to confirm the presence of tiamulin-resistant isolates in Spain. For these purposes, we performed biochemical tests in combination with diagnostic PCR analysis for the identification of Brachyspira spp. and for detection of the smpA/smpB gene. We also used antimicrobial susceptibility tests, random amplified polymorphic DNA (RAPD) and a new pulsed-field gel electrophoresis (PFGE) protocol. The combination of RAPD and PFGE allowed the study of epidemiological relationships. Both indole-negative and tiamulin-resistant isolates of B. hyodysenteriae are reported in Spain for the first time. The genetic analyses indicated a relationship between these Spanish isolates and indole-negative isolates previously obtained from Germany and Belgium.

[(18)F-FDG PET-CT and respiratory synchronization: effect in the detection and catalogation of pulmonary lesions]. / (18)F-FDG PET-TAC y sincronización respiratoria: efecto en la detección y catalogación de lesiones pulmonares.

UNLABELLED: The respiratory movement reduces the sensitivity in the detection of pulmonary lesions. The synchronized acquisition of PET with respiratory movement (4D) can reduce this inconvenient. Our objective was assess the effect of 4D PET-CT in the metabolic activity of (18)F FDG and final classification of pulmonary lesions. MATERIAL AND METHODS: 12 patients with 18 pulmonary lesions with sizes within 0.8-4cm were assessed. The maximum SUV was obtained in the imaging acquired in standard conditions (3D) and the obtained in the respiratory period with higher metabolic activity in 4D images. The difference of percentage between both values was calculated. Moreover were evaluated the changes of the classification of pulmonary nodes (benign or malignant) obtained from the assessment of 4D and 3D PET images. RESULTS: 17/18 pulmonary lesions showed an increase in the SUV(max) value in the 4D with respect to 3D image. 5 lesions showed SUV(max) values >2.5 in 4D image and <2.5 in 3D image. From these 3 were correctly catalogued as malignant with 4D although the number of false positive increased to 2. CONCLUSION: (18)F-FDG 4D PET-CT shows values of metabolic activity more realistic allowing the correct classification reducing the false negative although increasing the false positive.

[Usefulness of ventricular function values obtained using post-stress gated-SPECT in a diabetic population with clinical suspicion of ischaemic heart disease]. / Utilidad de los valores de función ventricular obtenidos mediante gated-SPECT post-estrés en población diabética con sospecha clínica de cardiopatía isquémica.

OBJECTIVE: To assess the clinical usefulness of left ventricular function values obtained using post-stress myocardial perfusion gated-SPECT in diabetic patients with suspected ischaemic heart disease (IHD). MATERIALS AND METHODS: Sixty-one patients with diabetes mellitus (DM), with clinical suspicion of IHD and no previous history of heart disease were studied. Ergometric or pharmacological post-stress myocardial perfusion gated-SPECT was performed on all patients. The relationship between the ejection fraction values and ventricular volumes, and the perfusion study results, final diagnosis, severity of the perfusion defects and the clinical evolution was studied. The mean follow-up time was 14 months. RESULTS; All the ventricular function values independently showed significant differences between the groups with a normal and pathological perfusion study, and between groups with a final diagnosis of IHD and non-IHD. After multivariate logistic regression, the end-diastolic volume (EDV) was the only value which showed a statistical association with the pathological perfusion study, its severity and the final diagnosis of IHD. No statistical association was observed between the ventricular function values and the occurrence of cardiac events. CONCLUSIONS: All the ventricular function values obtained by gated-SPECT added diagnostic information to the post-stress myocardial perfusion study in the diabetic population with suspected IHD; however, only EDV showed a statistical association with the pathological perfusion study, severity of defects and the final diagnosis of IHD.

Hallazgos incidentales en medicina genómica / Incidental Findings in Genomic Medicine

Las técnicas de Biología Molecular de última generación, como es la secuenciación masiva en paralelo o NGS (Next Generation Sequencing), permite obtener gran cantidad de información genómica, la cual muchas veces va más allá de la detección de una variante patogénica en un gen que explique la patología (hallazgo primario). Es así como surgió desde hace años la discusión internacional respecto a la decisión a tomar frente a los hallazgos secundarios accionables, es decir, aquellos hallazgos de variantes clasificadas como patogénicas o probablemente patogénicas que no están relacionadas con el fenotipo del paciente, pero que tiene alguna medida preventiva o tratamiento posible y, por lo tanto, podría ser de utilidad para la salud del paciente. Luego de revisar la bibliografía internacional y debatir entre los expertos del Hospital de Pediatría Garrahan, se logró establecer una política institucional y reforzar el hecho de que se trata de una disciplina multidisciplinaria. Así, fue posible definir que solo se atenderá las cuestiones relacionadas con la edad pediátrica, dejando para un tratamiento posterior aquellas variantes detectadas en genes que sean accionables en edad adulta. En el Hospital Garrahan, ha sido posible definir claramente cómo proceder frente a los hallazgos secundarios, al adaptar el consentimiento informado a esta necesidad, definiendo cuándo serán informados, y sabiendo que serán buscados intencionalmente en los genes clínicamente accionables enlistados en la última publicación del American College of Medical Genetics and Genomics, siempre y cuando el paciente/padre/tutor lo consienta (AU)

The latest generation of molecular biology techniques, including massive parallel sequencing or NGS (Next Generation Sequencing), allows us to obtain a whealth of genomic information, which often goes beyond the detection of a pathogenic variant in a gene that explains the pathology (primary finding). As a result, an international discussion has arisen over the years regarding the decision-making concerning actionable secondary findings, it means, those findings of variants classified as pathogenic or probably pathogenic that are not related to the patient's phenotype, but which have some possible preventive measure or treatment and, therefore, could be useful for the patient's health. After reviewing the international literature and discussing among the experts of the Hospital de Pediatría Garrahan, an institutional policy was established and the concept that this is a multidisciplinary discipline was reinforced. Consequently, it has been defined that only issues related to children will be addressed, reserving those variants detected in genes that are actionable in adulthood for later treatment. At Garrahan Hospital, we were able to clearly define how to proceed with secondary findings by adapting the informed consent to this need, defining when they will be reported, and knowing that they will be intentionally searched for in the clinically actionable genes listed in the latest publication of the American College of Medical Genetics and Genomics, as long as the patient/parent/guardian consents (AU)

Enfermedad mínima residual en leucemia mieloide aguda no promielocítica: Resultados preliminares de un estudio colaborativo internacional / Minimal residual disease in non-myelocytic acute myeloid leukemia: preliminary results of an international collaborative study

A pesar de los avances en los protocolos de tratamiento y en las medidas de soporte en pacientes con Leucemia Mieloide Aguda (LMA), 27% presentan recaídas de la enfermedad. Esto se debe, entre otras causas, a la persistencia de pequeñas cantidades de células malignas (blastos) resistentes a la terapia. Estas pequeñas cantidades de blastos remanentes se denominan Enfermedad Mínima Residual (EMR). La determinación de EMR requiere de técnicas no solo muy sensibles, sino también específicas, y permite evaluar la respuesta individual a la terapia. La introducción de la EMR como parámetro de respuesta y estratificación está bien definida en Leucemia Linfoblástica Aguda (LLA). Por el contrario, aunque existen publicaciones sobre el impacto pronóstico de la EMR en LMA, aún no se encuentra incluida en forma sistemática en los protocolos nacionales actuales, entre otros motivos, por lo laborioso de la determinación y por la necesidad de validación de la misma. Debe tenerse en cuenta que el inmunofenotipo de los blastos mieloides suele ser más heterogéneo que el de los blastos en LLA, presentando, en muchos casos, subpoblaciones diferentes entre sí, lo cual dificulta su detección certera y no hay consenso definido en cuanto a la metodología más eficaz. En este trabajo describimos una nueva estrategia de marcación y análisis estandarizada en un estudio multicéntrico internacional para LMA y la utilidad de la EMR como parámetro de respuesta y de estratificación. Asimismo, detallamos los resultados preliminares de nuestra cohorte de pacientes (AU)

Despite the improvement in treatment and supportive care of patients with Acute Myeloid Leukemia (AML), 27% of them relapse. This is due to the persistence of small amounts of malignant cells (blasts) resistant to therapy, among other causes. These small amounts of blasts are called Minimal Residual Disease (MRD). The determination of MRD requires not only techniques with high sensitivity but also with high specificity, and allows to evaluate the individual response to treatment. The introduction of MRD as a response parameter is well established in Acute Lymphoblastic Leukemia (ALL), and it is used in current stratification protocols. On the other hand, even though there are some reports regarding the prognostic impact of MRD in AML, it is still not included in the current national protocols due to the lack of validation of the determination, among other causes. This is due to the fact that the immunophenotype of myeloid blasts is more heterogeneous than in ALL, presenting different subpopulations, which difficults their accurate detection. Thus, there is still no consensus regarding the most effective approach. In this article, we describe a new staining and analysis strategy standardized by an international multicentric study, and the utility of EMR as a response and stratification parameter. Additionally, we show the preliminary results of our patient cohort. (AU)

Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives.

Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results: FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions: The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.