Nucleotide Limitation Results in Impaired Photosynthesis, Reduced Growth and Seed Yield Together with Massively Altered Gene Expression.

Nucleotide limitation and imbalance is a well-described phenomenon in animal research but understudied in the plant field. A peculiarity of pyrimidine de novo synthesis in plants is the complex subcellular organization. Here, we studied two organellar localized enzymes in the pathway, with chloroplast aspartate transcarbamoylase (ATC) and mitochondrial dihydroorotate dehydrogenase (DHODH). ATC knock-downs were most severely affected, exhibiting low levels of pyrimidine nucleotides, a low energy state, reduced photosynthetic capacity and accumulation of reactive oxygen species. Furthermore, altered leaf morphology and chloroplast ultrastructure were observed in ATC mutants. Although less affected, DHODH knock-down mutants showed impaired seed germination and altered mitochondrial ultrastructure. Thus, DHODH might not only be regulated by respiration but also exert a regulatory function on this process. Transcriptome analysis of an ATC-amiRNA line revealed massive alterations in gene expression with central metabolic pathways being downregulated and stress response and RNA-related pathways being upregulated. In addition, genes involved in central carbon metabolism, intracellular transport and respiration were markedly downregulated in ATC mutants, being most likely responsible for the observed impaired growth. We conclude that impairment of the first committed step in pyrimidine metabolism, catalyzed by ATC, leads to nucleotide limitation and by this has far-reaching consequences on metabolism and gene expression. DHODH might closely interact with mitochondrial respiration, as seen in delayed germination, which is the reason for its localization in this organelle.

Nucleotide Imbalance, Provoked by Downregulation of Aspartate Transcarbamoylase Impairs Cold Acclimation in Arabidopsis.

Aspartate transcarbamoylase (ATC) catalyzes the first committed step in pyrimidine de novo synthesis. As shown before, mutants with 80% reduced transcript and protein levels exhibit reduced levels of pyrimidine metabolites and thus nucleotide limitation and imbalance. Consequently, reduced photosynthetic capacity and growth, accompanied by massive transcriptional changes, were observed. Here, we show that nucleotide de novo synthesis was upregulated during cold acclimation of Arabidopsis thaliana (ecotype Columbia, Col-0) plants, but ATC knockdown mutants failed to acclimate to this condition as they did not accumulate neutral sugars and anthocyanins. A global transcriptome analysis revealed that most of the transcriptional changes observed in Col-0 plants upon cold exposure were also evident in ATC knockdown plants. However, several responses observed in cold-treated Col-0 plants could already be detected in knockdown plants when grown under standard conditions, suggesting that these mutants exhibited typical cold responses without prior cold stimulation. We believe that nucleotide signaling is involved in "cold-like priming" and "cold acclimation" in general. The observed transcript levels of genes involved in central carbon metabolism and respiration were an exception to these findings. These were upregulated in the cold but downregulated in warm-grown ATC mutants.

Microbial impact to environmental toxicants Ni(II) and Co(II): Joint toxicity and cellular response in Paramecium.

Cobalt (Co) and Nickel (Ni) are increasingly found in our environment. We analysed their combined toxicity and uptake mechanisms in the early food chain by studying bacteria and the bacterivorous ciliate Paramecium as a primary consumer. We exposed both species to these metals to measure the toxicity, uptake and transfer of metals from bacteria to Paramecium. We found that Ni is more toxic than Co, and that toxicity increases for both metals when (i) food bacteria are absent and (ii) both metals are applied in combination. The cellular content in bacteria after exposure shows a concentration dependent bias for either Ni or Co. Comparing single treatment and joint exposure, bacteria show increased levels of both metals when these are both exposed. To imitate the basic level of the food chain, we fed these bacteria to paramecia. The cellular content shows a similar ratio of Nickel and Cobalt as in food bacteria. This is different to the direct application of both metals to paramecia, where Cobalt is enriched over Nickel. This indicates that bacteria can selectively pre-accumulate metals for introduction into the food chain. We also analysed the transcriptomic response of Paramecium to sublethal doses of Nickel and Cobalt to gain insight into their toxicity mechanisms. Gene ontology (GO) analysis indicates common deregulated pathways, such as ammonium transmembrane transport and ubiquitine-associated protein degradation. Many redox-related genes also show deregulation of gene expression, indicating cellular adaptation to increased RONS stress. This suggests that both metals may also target the same cellular pathways and this is consistent with the increased toxicity of both metals when used together. Our data reveal complex ecotoxicological pathways for these metals and highlights the different parameters for their fate in the ecosystem, in the food chain and their ecotoxicological risk after environmental contamination.

Effectively Conducting Oncology Clinical Trials During the COVID-19 Pandemic.

PURPOSE: Clinical trial enrollment has declined globally as a result of the coronavirus disease 2019 (COVID-19) pandemic. This underscores the importance of structured methods to continue critical medical research safely and efficiently. METHODS AND MATERIALS: We report the effect of a phased trial reopening strategy, remote research staffing, and telemedicine on cancer trial enrollment at one of the largest radiation oncology academic cancer centers. In phase 1, trials investigating definitive therapeutic benefit were opened, followed by trials not increasing patient exposure or pulmonary toxicity risk in phase 2. During phase 2.5, multicenter trials reopened and limited research staff were allowed on site. RESULTS: Despite initial enrollment declines during the early pandemic, the percentage of new patients enrolling in clinical trials from March to August 2020 was 8.8%, and represented a 10.5% relative increase from 2019. Monthly accrual enrollment from March to August 2019 ranged from 42 to 71, compared with enrollment during COVID-19 from 23 to 73 patients (P < .001). CONCLUSIONS: Through a phased approach to trial reopening and adaptive techniques, the division of radiation oncology maintained cancer trial accrual during the COVID-19 pandemic. The experience may help centers maintain accrual, preserve clinical trial integrity, and minimize risk to patients and staff.

Nucleus-mitochondria positive feedback loop formed by ERK5 S496 phosphorylation-mediated poly (ADP-ribose) polymerase activation provokes persistent pro-inflammatory senescent phenotype and accelerates coronary atherosclerosis after chemo-radiation.

The incidence of cardiovascular disease (CVD) is higher in cancer survivors than in the general population. Several cancer treatments are recognized as risk factors for CVD, but specific therapies are unavailable. Many cancer treatments activate shared signaling events, which reprogram myeloid cells (MCs) towards persistent senescence-associated secretory phenotype (SASP) and consequently CVD, but the exact mechanisms remain unclear. This study aimed to provide mechanistic insights and potential treatments by investigating how chemo-radiation can induce persistent SASP. We generated ERK5 S496A knock-in mice and determined SASP in myeloid cells (MCs) by evaluating their efferocytotic ability, antioxidation-related molecule expression, telomere length, and inflammatory gene expression. Candidate SASP inducers were identified by high-throughput screening, using the ERK5 transcriptional activity reporter cell system. Various chemotherapy agents and ionizing radiation (IR) up-regulated p90RSK-mediated ERK5 S496 phosphorylation. Doxorubicin and IR caused metabolic changes with nicotinamide adenine dinucleotide depletion and ensuing mitochondrial stunning (reversible mitochondria dysfunction without showing any cell death under ATP depletion) via p90RSK-ERK5 modulation and poly (ADP-ribose) polymerase (PARP) activation, which formed a nucleus-mitochondria positive feedback loop. This feedback loop reprogramed MCs to induce a sustained SASP state, and ultimately primed MCs to be more sensitive to reactive oxygen species. This priming was also detected in circulating monocytes from cancer patients after IR. When PARP activity was transiently inhibited at the time of IR, mitochondrial stunning, priming, macrophage infiltration, and coronary atherosclerosis were all eradicated. The p90RSK-ERK5 module plays a crucial role in SASP-mediated mitochondrial stunning via regulating PARP activation. Our data show for the first time that the nucleus-mitochondria positive feedback loop formed by p90RSK-ERK5 S496 phosphorylation-mediated PARP activation plays a crucial role of persistent SASP state, and also provide preclinical evidence supporting that transient inhibition of PARP activation only at the time of radiation therapy can prevent future CVD in cancer survivors.

[Prevalence and clinico-pathological characteristics in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma in a high complexity hospital in Cali, Columbia]. / Prevalencia y características clínicas y anatomopatológicas de los pacientes con diagnóstico de linfoma difuso de células B grandes y positivo al virus Epstein-Barr en un hospital de alta complejidad en Cali (Colombia).

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) accounts for 35% of non-Hodgkin lymphoma and its incidence increases with age. Epstein Barr virus (EBV) is widely spread worldwide. There is a 10% association between EBV and DLBCL in immunocompetent patients; this type of malignancy has a high prevalence in Latin American countries. OBJECTIVE: Estimate the percentage of association between DLBCL and EBV patients, describing demographics, clinical and immunological features, as well as phenotype and clinical outcome in a high complexity healthcare institution in Colombia. MATERIALS AND METHODS: This is an analytic observational study from an historical cohort. Clinical and pathological records were revised among DLBCL patients and subsequent in-situ hybridization was performed for EBV detection. A descriptive analysis of the data was carried out. RESULTS: From 2011 to 2017, 55 DLBCL patients were identified. 16% were positive on ISH for EBV, most of which belonged to the non-germinal center B-cell immunophenotype (89%), with a nodal presentation (56%). DLBCL EBV positive was more prevalent among males (67%) and in younger patients (median of 48 years) where the mortality rate was 56%. CONCLUSIONS: DLBCL patients positive for EBV are more prone to belong to the non-germinal center B-cell immunophenotype which, according to our findings, is associated with a younger age and worse prognosis. Presently, EBER in-situ hybridization is not a part of routine tests, but we recommend its inclusion in the pathology package for DLBCL patients, as it can influence clinical outcomes.

Three-Year Outcomes With Hypofractionated Versus Conventionally Fractionated Whole-Breast Irradiation: Results of a Randomized, Noninferiority Clinical Trial.

PURPOSE: The adoption of hypofractionated whole-breast irradiation (HF-WBI) remains low, in part because of concerns regarding its safety when used with a tumor bed boost or in patients who have received chemotherapy or have large breast size. To address this, we conducted a randomized, multicenter trial to compare conventionally fractionated whole-breast irradiation (CF-WBI; 50 Gy/25 fx + 10 to 14 Gy/5 to 7 fx) with HF-WBI (42.56 Gy/16 fx + 10 to 12.5 Gy/4 to 5 fx). PATIENTS AND METHODS: From 2011 to 2014, 287 women with stage 0 to II breast cancer were randomly assigned to CF-WBI or HF-WBI, stratified by chemotherapy, margin status, cosmesis, and breast size. The trial was designed to test the hypothesis that HF-WBI is not inferior to CF-WBI with regard to the proportion of patients with adverse cosmetic outcome 3 years after radiation, assessed using the Breast Cancer Treatment Outcomes Scale. Secondary outcomes included photographically assessed cosmesis scored by a three-physician panel and local recurrence-free survival. Analyses were intention to treat. RESULTS: A total of 286 patients received the protocol-specified radiation dose, 30% received chemotherapy, and 36.9% had large breast size. Baseline characteristics were well balanced. Median follow-up was 4.1 years. Three-year adverse cosmetic outcome was 5.4% lower with HF-WBI ( Pnoninferiority = .002; absolute risks were 8.2% [n = 8] with HF-WBI v 13.6% [n = 15] with CF-WBI). For those treated with chemotherapy, adverse cosmetic outcome was higher by 4.1% (90% upper confidence limit, 15.0%) with HF-WBI than with CF-WBI; for large breast size, adverse cosmetic outcome was 18.6% lower (90% upper confidence limit, -8.0%) with HF-WBI. Poor or fair photographically assessed cosmesis was noted in 28.8% of CF-WBI patients and 35.4% of HF-WBI patients ( P = .31). Three-year local recurrence-free survival was 99% with both HF-WBI and CF-WBI ( P = .37). CONCLUSION: Three years after WBI followed by a tumor bed boost, outcomes with hypofractionation and conventional fractionation are similar. Tumor bed boost, chemotherapy, and larger breast size do not seem to be strong contraindications to HF-WBI.

Impact of Statin Use on Outcomes in Triple Negative Breast Cancer.

Purpose: We sought to investigate if the use of HMG Co-A reductase inhibitors (statins) has an impact on outcomes among patients with triple negative breast cancer (TNBC). Methods: We reviewed the cases of women with invasive, non-metastatic TNBC, diagnosed 1997-2012. Clinical outcomes were compared based on statin use (defined as ever use during treatment vs. never use). We identified a subset of women for whom a 5-value lipid panel (5VLP) was available, including total cholesterol, low density lipoprotein, high density lipoprotein, very low density lipoprotein, and triglycerides. The Kaplan-Meier method was used to estimate median overall survival (OS), distant metastases-free survival (DMFS), and local-regional recurrence-free survival (LRRFS). A Cox proportional hazards regression model was used to test the statistical significance of prognostic factors. Results: 869 women were identified who met inclusion criteria, with a median follow-up time of 75.1 months (range 2.4-228.9 months). 293 (33.7%) patients used statins and 368 (42.3%) had a 5VLP. OS, DMFS, and LRRFS were not significant based on statin use or type. Controlling for the 5VLP values, on multivariable analysis, statin use was significantly associated with OS (HR 0.10, 95% CI 0.01-0.76), but not with DMFS (HR 0.14, 95% CI 0.01-1.40) nor LRRFS (HR 0.10 95% CI 0.00-3.51). Conclusions: Statin use among patients with TNBC is not associated with improved OS, although it may have a benefit for a subset of patients. Prospective assessment would be valuable to better assess the potential complex correlation between clinical outcome, lipid levels, and statin use.

[Polydactyly, holoprosencephaly, cleft lip and cleft palate are not always what they seem: Case report]. / Polidactilia, holoprosencefalia, labio y paladar hendido: no siempre es lo que parece.

We report a male infant with midline defects, congenital heart disease and polydactyly, features suggestive of trisomy 13. However, the report of the karyotype was normal. By clinical findings the final diagnosis was likely to be Pseudotrisomy 13. Although the prognosis is poor in both conditions, the genetic study is always necessary to establish an adequate genetic counseling. Although there are syndromes with similar presentation as Meckel syndrome, Smith-Lemli-Opitz syndrome, Pallister-Hall syndrome and hydrolethalus, it is possible to make a diagnostic approach based on the perinatal history, birth weight, survival time, and some characteristics of each syndrome. However, limitations may exist to perform genetic studies in some countries, therefore the clinical criteria may be relevant.

Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial.

IMPORTANCE: The most appropriate dose fractionation for whole-breast irradiation (WBI) remains uncertain. OBJECTIVE: To assess acute and 6-month toxic effects and quality of life (QOL) with conventionally fractionated WBI (CF-WBI) vs hypofractionated WBI (HF-WBI). DESIGN, SETTING, AND PARTICIPANTS: Unblinded randomized trial of CF-WBI (n = 149; 50.00 Gy/25 fractions + boost [10.00-14.00 Gy/5-7 fractions]) vs HF-WBI (n = 138; 42.56 Gy/16 fractions + boost [10.00-12.50 Gy/4-5 fractions]) following breast-conserving surgery administered in community-based and academic cancer centers to 287 women 40 years or older with stage 0 to II breast cancer for whom WBI without addition of a third field was recommended; 76% of study participants (n = 217) were overweight or obese. Patients were enrolled from February 2011 through February 2014 and observed for a minimum of 6 months. INTERVENTIONS: Administration of CF-WBI or HF-WBI. MAIN OUTCOMES AND MEASURES: Physician-reported acute and 6-month toxic effects using National Cancer Institute Common Toxicity Criteria, and patient-reported QOL using the Functional Assessment of Cancer Therapy for Patients with Breast Cancer (FACT-B). All analyses were intention to treat, with outcomes compared using the χ2 test, Cochran-Armitage test, and ordinal logistic regression. RESULTS: Of 287 participants, 149 were randomized to CF-WBI and 138 to HF-WBI. Treatment arms were well matched for baseline characteristics, including FACT-B total score (HF-WBI, 120.1 vs CF-WBI, 118.8; P = .46) and individual QOL items such as somewhat or more lack of energy (HF-WBI, 38% vs CF-WBI, 39%; P = .86) and somewhat or more trouble meeting family needs (HF-WBI, 10% vs CF-WBI, 14%; P = .54). Maximum physician-reported acute dermatitis (36% vs 69%; P < .001), pruritus (54% vs 81%; P < .001), breast pain (55% vs 74%; P = .001), hyperpigmentation (9% vs 20%; P = .002), and fatigue (9% vs 17%; P = .02) during irradiation were lower in patients randomized to HF-WBI. The rate of overall grade 2 or higher acute toxic effects was less with HF-WBI than with CF-WBI (47% vs 78%; P < .001). Six months after irradiation, physicians reported less fatigue in patients randomized to HF-WBI (0% vs 6%; P = .01), and patients randomized to HF-WBI reported less lack of energy (23% vs 39%; P < .001) and less trouble meeting family needs (3% vs 9%; P = .01). Multivariable regression confirmed the superiority of HF-WBI in terms of patient-reported lack of energy (odds ratio [OR], 0.39; 95% CI, 0.24-0.63) and trouble meeting family needs (OR, 0.34; 95% CI, 0.16-0.75). CONCLUSIONS AND RELEVANCE: Treatment with HF-WBI appears to yield lower rates of acute toxic effects than CF-WBI as well as less fatigue and less trouble meeting family needs 6 months after completing radiation therapy. These findings should be communicated to patients as part of shared decision making. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01266642.

Educación sexual en mujeres adolescentes en una zona marginal urbana de México / Sexual education in adolescent women in a urban marginal zone of Mexico / Educação sexual em mulheres adolescentes em uma área marginal urbana do México

Objetivo: incrementar los conocimientos sobre sexualidad de mujeres adolescentes de tres planteles de educación primaria\r\nmediante una intervención educativa en el oriente de la ciudad de San Luis Potosí, México. Método: estudio cuasi-experimental.\r\nEl trabajo se desarrolló en tres etapas: primero se realizó una medición basal de los conocimientos; luego una intervención educativa\r\nde once sesiones y por último una segunda medición. Se utilizó el programa SPSS Versión 20.0 para el procesamiento y análisis\r\nde los datos. Con la prueba t de Student se verificó si hubo incremento en el nivel de conocimientos. Resultados: participaron\r\n168 mujeres de quinto y sexto grado de primaria. En general hubo un incremento de los conocimientos sobre sexualidad debido\r\na la intervención educativa realizada. Conclusión: es importante realizar este tipo de intervenciones en la población adolescente\r\na fin de incrementar los conocimientos sobre sexualidad. Se recomienda dar seguimiento a las participantes con miras a identificar\r\nsus conductas sexuales.

Objective: To increase knowledge about adolescent sexuality\r\nin three elementary schools through an educational program\r\nin San Luis Potosí, México. Method: Quasi-experimental study.\r\nA three stage program: First, the establishment of a baseline\r\nmeasurement of knowledge; secondly, the implementation\r\nof an eleven session educational program; thirdly, a second\r\nmeasurement of knowledge. The 20.0 Version of the SPSS\r\nprogram was used for the processing and analysis of the data.\r\nWith the Student's T-test was verified if there was an increase\r\nin the level of knowledge. Results: 168 elementary school girls\r\nfrom fifth and sixth grade participated. In general there was\r\nan increase in knowledge about sexuality due to the educational\r\nintervention carried out. Conclusion: For the purpose of\r\nincreasing knowledge about sexuality in the adolescent population,\r\nit is important to perform this type of intervention. It is\r\nnecessary to follow up with the participants in order to identify\r\ntheir sexual conduct.

aumentar o conhecimento da sexualidade de\r\nmulheres adolescentes de três escolas primárias através de uma\r\nintervenção educativa em San Luis Potosí, México. Método:\r\nestudo quase experimental. Incluem três etapas: uma primeira\r\nmedida de conhecimento; uma intervenção educativa de onze\r\nsessões; e uma segunda medida. O programa SPSS Versão 20.0\r\nfoi utilizado para o processamento e análise dos dados. Com\r\no teste T-student verificou-se se houve aumento no nível de\r\nconhecimento. Resultados: participaram 168 mulheres do\r\nquinto e sexto ano de ensino fundamental. Em geral, houve\r\num aumento no conhecimento sobre sexualidade devido à\r\nintervenção educativa realizada. Conclusão: é importante\r\nrealizar esse tipo de intervenção na população adolescente,\r\na fim de reduzir a gravidez na adolescência. As participantes\r\nterão que ser acompanhadas para identificar seus comportamentos\r\nsexuais.

¿Qué saben los pacientes con dolor crónico no oncológico sobre los opioides que les formulan? / What do patients with chronic non-cancer pain know about the opiates that they are prescribed?

Como el dolor es la primera causa de consulta médica en el mundo, el uso de opioides para el manejo del tipo crónico no oncológico ha aumentado y la falta de conocimiento favorece el uso inadecuado. Objetivo: Se describen los riesgos, efectos adversos, actitudes y prácticas que tienen los pacientes ambulatorios formulados con opioides para el manejo de dolor crónico no oncológico en un hospital de cuarto nivel en Bogotá DC, Colombia. Estudio descriptivo de corte transversal en dos fases, la primera la construcción y aprobación del cuestionario por un grupo evaluador usando metodología Delphi y la segunda su diligenciamiento en la población de interés: 81 pacientes entre septiembre y diciembre de 2014; sexo femenino 71,6%, edad promedio 56,6 años (DE: 15,2) y el diagnóstico más frecuente fue dolor lumbar (34,6%). El opioide con mayor formulación fue hidrocodona (24,1%).Resultados: El efecto secundario más reconocido fue estreñimiento (60,5%), 28,4% no saben si existe restricción para conducir vehículos y el 34,6% creen que es permitido; un 60,5% consultan de nuevo en caso de persistencia del dolor. El 23,5% guarda la medicación sobrante después de un cambio o suspensión, mientras que el 9,9% la regala.Conclusiones. Hay fallas en el conocimiento de los pacientes en cuanto a la limitación de actividades, efectos secundarios y disposición de la medicación opioide sobrante.

As pain is the leading reason for medical consultation worldwide, the use of opioids in the management of non-cancer related chronic pain has increased, and poor patient knowledge has led to opioid misuse.Objective: We describe the risks, adverse effects, attitudes, and practices of out-patients prescribed with opioids for non-cancer related chronic pain in a fourth level hospital in Bogotá DC, Colombia. A two-phase descriptive cross-sectional study was conducted. First, a questionnaire, approved by an evaluating panel, was constructed using the Delphi methodology. Second, the questionnaire was applied in the study population: 81 patients between September and December 2014; females 71.6%, mean age 56.6 years (SD: 15.2), and back pain (34.6%) being the most frequent diagnosis. The most commonly prescribed opioid medication was hydrocodone (24.1%).Results: The most commonly recognised side effect was constipation (60.5%); 28.4% do not know if driving is restricted, and 34.6% believe driving is allowed; 6.5% again consulted again due to persistent pain. 23.5% keep the remaining medication after it is changed or stopped, while 9.9% gives it to someone else.Conclusions: Poor patient knowledge on restricted activities, potential side effects and proper opioid medication disposal was detected.

Polidactilia, holoprosencefalia, labio y paladar hendido: no siempre es lo que parece / Polydactyly, holoprosencephaly, cleft lip and cleft palate are not always what they seem: Case report

Reportamos un neonato masculino con defectos de línea media, cardiopatía congénita y polidactilia, características sugestivas de trisomía 13. Sin embargo, el reporte de cariotipo fue normal. Por hallazgos clínicos, el diagnóstico final probable fue pseudotrisomía 13. Aunque el pronóstico de ambas condiciones es pobre, los estudios genéticos siempre son necesarios para establecer una adecuada asesoría genética. Si bien hay síndromes con presentación similar, como el de Meckel, el de Smith-Lemli- Opitz, el de Pallister-Hall y el hidroletalus, se puede realizar una aproximación diagnóstica basada en los antecedentes perinatales, el peso al nacer, el tiempo de supervivencia y algunos rasgos característicos de cada síndrome. Además, pueden existir, en algunos países, limitaciones para realizar estudios genéticos, por lo que los criterios clínicos pueden ser relevantes.

We report a male infant with midline defects, congenital heart disease and polydactyly, features suggestive of trisomy 13. However, the report of the karyotype was normal. By clinical findings the final diagnosis was likely to be Pseudotrisomy 13. Although the prognosis is poor in both conditions, the genetic study is always necessary to establish an adequate genetic counseling. Although there are syndromes with similar presentation as Meckel syndrome, Smith-Lemli-Opitz syndrome, Pallister-Hall syndrome and hydrolethalus, it is possible to make a diagnostic approach based on the perinatal history, birth weight, survival time, and some characteristics of each syndrome. However, limitations may exist to perform genetic studies in some countries, therefore the clinical criteria may be relevant.

Prevalencia y características clínicas y anatomopatológicas de los pacientes con diagnóstico de linfoma difuso de células B grandes y positivo al virus Epstein-Barr en un hospital de alta complejidad en Cali (Colombia) / Prevalence and clinico-pathological characteristics in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma in a high complexity hospital in Cali, Columbia

INTRODUCCIÓN: El linfoma difuso de células B grandes (LDCBG) constituye el 35% de los linfomas no Hodgkin y su incidencia aumenta con la edad. El virus Epstein-Barr (VEB) está ampliamente distribuido a nivel mundial. La asociación entre el LDCBG y VEB está cerca del 10% en pacientes inmunocompetentes; este tipo de linfoma tiene alta prevalencia en países de Latinoamérica. OBJETIVO: Conocer la frecuencia del LDCBG asociado al VEB y describir sus características demográficas, clínicas, inmunofenotípicas y desenlace de los pacientes en un centro de alta complejidad en Cali (Colombia). MATERIALES Y MÉTODOS: Estudio observacional descriptivo de una cohorte histórica. Se revisaron los registros clínicos y de anatomía patológica de pacientes con diagnóstico de LDCBG y se realizó la hibridación in situ para la detección del VEB (EBER). Se realizó un análisis descriptivo. RESULTADOS: Entre 2011 y 2017 se revisó la historia clínica de 55 pacientes con diagnóstico de LDCBG. El 16% fueron VEB positivos, los cuales fueron en su mayoría del subtipo no centro germinal (89%), con presentación nodal (56%); hubo mayor prevalencia en hombres (68%), menor edad de presentación (mediana 48 años) y muerte en el 56% de los casos. CONCLUSIONES: Los pacientes con LDCBG y VEB positivo presentan con mayor frecuencia el subtipo no centro germinal, el cual, según nuestros hallazgos, se presenta en pacientes más jóvenes y se asocia a peor pronóstico. El EBER no es un examen que se hace de rutina, por lo cual se recomienda realizar pruebas para la detección del VEB en pacientes con diagnóstico de LDCBG

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) accounts for 35% of non-Hodgkin lymphoma and its incidence increases with age. Epstein Barr virus (EBV) is widely spread worldwide. There is a 10% association between EBV and DLBCL in immunocompetent patients; this type of malignancy has a high prevalence in Latin American countries. OBJECTIVE: Estimate the percentage of association between DLBCL and EBV patients, describing demographics, clinical and immunological features, as well as phenotype and clinical outcome in a high complexity healthcare institution in Colombia. MATERIALS AND METHODS: This is an analytic observational study from an historical cohort. Clinical and pathological records were revised among DLBCL patients and subsequent in-situ hybridization was performed for EBV detection. A descriptive analysis of the data was carried out. RESULTS: From 2011 to 2017, 55 DLBCL patients were identified.16% were positive on ISH for EBV, most of which belonged to the non-germinal center B-cell immunophenotype (89%), with a nodal presentation (56%). DLBCL EBV positive was more prevalent among males (67%) and in younger patients (median of 48 years) where the mortality rate was 56%. CONCLUSIONS: DLBCL patients positive for EBV are more prone to belong to the non-germinal center B-cell immunophenotype which, according to our findings, is associated with a younger age and worse prognosis. Presently, EBER in-situ hybridization is not a part of routine tests, but we recommend its inclusion in the pathology package for DLBCL patients, as it can influence clinical outcomes

Nefropatía y dismorfismo globular en sedimento urinario / Nephropathy and urinary sediment in globular dysmorphism

Este trabajo de investigación tiene como objetivos describir la importancia de la cuantificación del dismorfismo globularen el sedimento urinario de pacientes con estudio histológico de biopsia renal, como ayuda diagnóstica de nefropatías, aligual que determinar la frecuencia de estas alteraciones y comparar los hallazgos del sedimento urinario con la biopsia.Las muestras fueron obtenidas de diez enfermos mayores de 18 años que acudieron a la unidad renal del Hospital de SanJosé, y a quienes se les realizó cuantificación de dismorfismo antes de la biopsia. De los diez pacientes analizados, dospresentaron dismorfismo globular menor del 50%, seis entre 51 y 80% y en dos fue mayor del 81%.Se observó que puede existir relación entre dismorfismo globular en sedimento urinario y nefropatías, sin embargo, serequieren estudios y pruebas diagnósticas mejor estructurados, con el fin de ampliar los conocimientos adquiridos sobreeste tema.