[Características demográficas y clínicas de los pacientes sometidos a artroscopia del manguito rotador del hombro: estudio observacional.] / Demographic and clinical characteristics of patients undergoing rotator cuff arthroscopy of the shoulder: an observational study.

OBJECTIVE: The most common cause of shoulder pain is clinical pictures related to rotator cuff problems. One of the most common treatments is arthroscopic surgery. The objective was to describe the clinical and epidemiological characteristics of patients undergoing this type of surgery in Spain. METHODS: A descriptive, observational and cross-sectional study with ninety participants was carried out. Data on age, sex, performance of work activity with overuse of upper limbs, body mass index (BMI), smoking habit, diagnosis of diabetes, performance of physical-sports activity and history of pre-surgical treatments were collected. Finally, a descriptive analysis of the variables and an analysis of correlations were carried out, using the Pearson and Spearman statistical test according to the type of variable. RESULTS: The mean age was 57.21 years with a standard deviation (SD) of 8.5 (95% CI, 55.41-59.00). Regarding their BMI, the mean was 28.49 with a SD of 4.9 (95% CI, 27.49-29.53), with 35.6% being obese (BMI greater than 30). The medical diagnosis of the subjects was 51.1% total rotator cuff tear. On the other hand, the intensity of physical activity was one hour or less per week in 87.8% of the sample. Finally, in relation to the previous physiotherapy treatment, 69.7% of the subjects had received some type of intervention. CONCLUSIONS: The demographic and clinical characteristics found are consistent with those of other previously studied populations, and the association factors between them endorse the previously mentioned risk factors, with advanced age gaining special importance.

OBJETIVO: La causa más común de dolor de hombro son los cuadros clínicos relacionados con problemas del manguito rotador. Uno de los tratamientos más habituales es la cirugía artroscópica. El objetivo del estudio fue describir las características clínicas y epidemiológicas de los pacientes sometidos a este tipo de cirugías en España. METODOS: Se realizó un estudio de tipo descriptivo, observacional y de corte transversal con noventa participantes. Se recogieron los datos de edad, sexo, realización de actividad laboral con sobreuso de miembros superiores (MMSS), índice de masa corporal (IMC), consumo de tabaco, diagnóstico de diabetes, realización de actividad física-deportiva y antecedentes de tratamientos prequirúrgicos. Finalmente, se realizó un análisis descriptivo de las variables y un análisis de correlaciones, mediante la prueba estadística de Pearson y Spearman según el tipo de variable. RESULTADOS: La media de edad fue de 57,21 años con una desviación estándar (DE) de 8,5 (Intervalo de Confianza [IC] del 95%, 55,41-59,00). En cuanto a su IMC, la media fue de 28,49 con una DE de 4,9 (IC del 95%, 27,49-29,53), siendo el 35,6% personas con obesidad (IMC mayor de 30). El diagnóstico médico de los sujetos fue en un 51,1% de rotura total del manguito rotador. Por otro lado, la intensidad de realización de actividad física fue de una hora o menos a la semana en el 87,8% de la muestra. Por último, en relación con el tratamiento previo de fisioterapia, el 69,7% de los sujetos habían recibido algún tipo de intervención. CONCLUSIONES: Las características demográficas y clínicas encontradas están en consonancia con las de otras poblaciones estudiadas previamente, y los factores de asociación entre ellas refrendan los factores de riesgo ya señalados previamente (edad, obesidad, sobreuso de MMSS), cobrando especial importancia la edad avanzada.

Genetic Profiling of Cell-Free DNA in Liquid Biopsies: A Complementary Tool for the Diagnosis of B-Cell Lymphomas and the Surveillance of Measurable Residual Disease.

PURPOSE: To assess the potential value of LiqBio as a complementary tool for diagnosis and surveillance of BCL. METHODS: This prospective multi-center study included 78 patients (25 follicular lymphomas (FL) and 53 large B-cell lymphomas (LBCL)). We performed next-generation sequencing (NGS) of cfDNA LiqBio and paired gDNA tissue biopsies at diagnosis and compared the mutational statuses. Also, through NGS of LiqBio, we identified MRD biomarkers and compared this novel LiqBio-MRD method with PET/CT in detecting MRD at follow-up. RESULTS: We identified mutations in 71% of LiqBio and 95% of tissue biopsies, and found a correlation between variant allele frequency of somatic mutations. Additionally, we identified mutations in 73% of LiqBio from patients with no available tissue samples or no mutations in them. Regarding the utility of LiqBio-MRD as a dynamic monitoring tool, when compared with the PET/CT method, a lower sensitivity was observed for LiqBio-MRD at 92.3% (vs. 100% for PET/CT), but a higher specificity of 91.3% (vs. 86.9% for PET/CT). CONCLUSION: Genetic profiling of tumor cfDNA in plasma LiqBio is a complementary tool for BCL diagnosis and MRD surveillance.

Expression of HMGCS2 in intestinal epithelial cells is downregulated in inflammatory bowel disease associated with endoplasmic reticulum stress.

Introduction: The Unfolded Protein Response, a mechanism triggered by the cell in response to Endoplasmic reticulum stress, is linked to inflammatory responses. Our aim was to identify novel Unfolded Protein Response-mechanisms that might be involved in triggering or perpetuating the inflammatory response carried out by the Intestinal Epithelial Cells in the context of Inflammatory Bowel Disease. Methods: We analyzed the transcriptional profile of human Intestinal Epithelial Cell lines treated with an Endoplasmic Reticulum stress inducer (thapsigargin) and/or proinflammatory stimuli. Several genes were further analyzed in colonic biopsies from Ulcerative Colitis patients and healthy controls. Lastly, we generated Caco-2 cells lacking HMGCS2 by CRISPR Cas-9 and analyzed the functional implications of its absence in Intestinal Epithelial Cells. Results: Exposure to a TLR ligand after thapsigargin treatment resulted in a powerful synergistic modulation of gene expression, which led us to identify new genes and pathways that could be involved in inflammatory responses linked to the Unfolded Protein Response. Key differentially expressed genes in the array also exhibited transcriptional alterations in colonic biopsies from active Ulcerative Colitis patients, including NKG2D ligands and the enzyme HMGCS2. Moreover, functional studies showed altered metabolic responses and epithelial barrier integrity in HMGCS2 deficient cell lines. Conclusion: We have identified new genes and pathways that are regulated by the Unfolded Protein Response in the context of Inflammatory Bowel Disease including HMGCS2, a gene involved in the metabolism of Short Chain Fatty Acids that may have an important role in intestinal inflammation linked to Endoplasmic Reticulum stress and the resolution of the epithelial damage.

[Teleophthalmology-based diabetic retinopathy screening in a rural health basic area]. / Cribado de la retinopatía diabética mediante teleoftalmología en una zona básica de salud rural.

OBJECTIVE: To investigate the prevalence of diabetic retinopathy in a rural health basic area, and to establish the type, the severity degree and the relationship with sex and with another cardiovascular risk factors. DESIGN: Cross-sectional or prevalence descriptive study. LOCATION: Rural health basic area in Spain. Primary health care level. PARTICIPANTS: 500 patients over 18 years old with diabetes. MAIN MEASUREMENTS: Study of the retina through retinography under mydriasis, according to the Joslin Vision Network protocol, with the incorporation of a diagnostic reading center. Correlation of the existence and severity of the retinopathy with the cardiovascular risk factors -smoking, hypertension and hyperlipidemia- and the characteristics of the diabetes -type, evolution time, treatment, metabolic control and renal function-. RESULTS: The findings showed a 16.4% prevalence, with no significant differences between both sexes. The variables smoking and high blood pressure were related to the existence of retinopathy, and the variable years of diabetes evolution was correlated to both the existence and the severity of the retinopathy. In the study, 9.6% of the affected people were preferentially referred to the ophthalmologists because of sight-threatening retinopathy, and 6.8% of the people studied were referred due to other ophthalmological pathologies. CONCLUSIONS: It is possible to do the ophthalmological follow-up of 82% of the population with diabetes in primary health care, involving its professionals and team-working with the ophthalmologists. It is paramount to consider diabetic retinopathy within the global context of the person with diabetes, relating diabetic retinopathy with the other microvascular complications and cardiovascular diseases.

"MiR-7 controls cholesterol biosynthesis through posttranscriptional regulation of DHCR24 expression".

Dysregulation of cholesterol homeostasis is associated with several pathologies including cardiovascular diseases and neurological disorders such as Alzheimer's disease (AD). MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of cholesterol metabolism. We previously established the role of miR-7 in regulating insulin resistance and amyloidosis, which represents a common pathological feature between type 2 diabetes and AD. We show here an additional metabolic function of miR-7 in cholesterol biosynthesis. We found that miR-7 blocks the last steps of the cholesterol biosynthetic pathway in vitro by targeting relevant genes including DHCR24 and SC5D posttranscriptionally. Intracranial infusion of miR-7 on an adeno-associated viral vector reduced the expression of DHCR24 in the brain of wild-type mice, supporting in vivo miR-7 targeting. We also found that cholesterol regulates endogenous levels of miR-7 in vitro, correlating with transcriptional regulation through SREBP2 binding to its promoter region. In parallel to SREBP2 inhibition, the levels of miR-7 and hnRNPK (the host gene of miR-7) were concomitantly reduced in brain in a mouse model of Niemann Pick type C1 disease and in murine fatty liver, which are both characterized by intracellular cholesterol accumulation. Taken together, the results establish a novel regulatory feedback loop by which miR-7 modulates cholesterol homeostasis at the posttranscriptional level, an effect that could be exploited for therapeutic interventions against prevalent human diseases.

Successful Pregnancy and Cancer Outcomes With Ipilimumab and Nivolumab for Metastatic Renal Cell Carcinoma: Case Report and Review of the Literature.

Pregnancy and cancer share CTLA-4 and PD-1/PD-L1 as some of the immunomodulatory pathways that reshape the immune system from a destructive response to a state of tolerance to the fetus and the tumor, respectively. Ipilimumab (anti-CTLA-4 inhibitor) and nivolumab (anti-PD-1 inhibitor) are used in combination for the treatment of metastatic renal cell carcinoma, and their use could theoretically result in an immune response against the fetus. Furthermore, these immune checkpoint inhibitors are immunoglobulin G antibodies that transfer from the mother to the fetus and may cause a direct toxicity. We present the first report of a metastatic renal cell carcinoma patient in which ipilimumab and nivolumab were successfully used starting in her first trimester of pregnancy, with sufficient follow-up to show favorable outcomes for both the mother and the child. We describe our management of this challenging case and we review the available evidence, coming from Developmental and Reproductive Toxicology Studies and case reports of metastatic melanoma patients.

Neurofibromatosis type 1 families with first-degree relatives harbouring distinct NF1 pathogenic variants. Genetic counselling and familial diagnosis: what should be offered?

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by pathogenic variants in NF1 Recently, NF1 testing has been included as a clinical criterion for NF1 diagnosis. Additionally, preconception genetic counselling in patients with NF1 focuses on a 50% risk of transmitting the familial variant as the risk of having a sporadic NF1 is considered the same as the general population. METHODS: 829 individuals, 583 NF1 sporadic cases and 246 patients with NF1 with documented family history, underwent genetic testing for NF1. Genotyping and segregation analysis of NF1 familial variants was determined by microsatellite analysis and NF1 sequencing. RESULTS: The mutational analysis of NF1 in 154 families with two or more affected cases studied showed the co-occurrence of two different NF1 germline pathogenic variants in four families. The estimated mutation rate in those families was 3.89×10-3, 20 times higher than the NF1 mutation rate (~2×10-4) (p=0.0008). Furthermore, the co-occurrence of two different NF1 germline pathogenic variants in these families was 1:39, 60 times the frequency of sporadic NF1 (1:2500) (p=0.003). In all cases, the de novo NF1 pathogenic variant was present in a descendant of an affected male. In two cases, variants were detected in the inherited paternal wild-type allele. CONCLUSIONS: Our results, together with previous cases reported, suggest that the offspring of male patients with NF1 could have an increased risk of experiencing de novo NF1 pathogenic variants. This observation, if confirmed in additional cohorts, could have relevant implications for NF1 genetic counselling, family planning and NF1 genetic testing.

Transfusion needs in patients admitted for fracture of femur. / Necesidades transfusionales en pacientes ingresados por fractura de fémur.

OBJECTIVE: To determine the variables and predictive factors associated with the administration and frequency of the allogenic blood transfusion (ABT) on patients diagnosed with fracture of femur requiring surgical intervention. The secondary objective was to describe the frequency and quantity of ABT on those patients. METHOD: A retrospective transversal observational study was performed on patients admitted to the Sagrat Cor hospital of Barcelona with a diagnosis of fractured femur that required surgical intervention in 2016. Several demographic variables were gathered along with the clinical data and outcome of transfused and non-transfused patients, including the type of fracture. RESULTS: The overall sample was 257 patients. Of the patients studied, 52.9% required blood transfusion support. Patients who required ABT had haemoglobin values on admission of 11.01 gdl while those that did not require transfusion had an average value of 12.97 g/dl. Of the patients, 42.8% were on anticoagulant and/or antiplatelet therapy before the fracture occurred. CONCLUSIONS: More than half the patients admitted for fracture of femur received blood transfusion. The data collected showed that the hospital transfusion policy offered satisfactory results. Factors associated with the need for ABT were haemoglobin levels on admission and the type of fracture. Age and ASA risk (classification system of the American Society of Anesthesiologists) were also risk factors for ABT. This information could be useful for blood saving protocols. Finally, we think that it is important that all patients that are hospitalised with a diagnosis of fracture of femur and require surgery have a blood reserve request made, given that a high percentage of them, at any time during their stay, will be transfused.

Craniopharyngiomas: A clinicopathological and molecular study of 52 cases - Experience in the Complejo Hospitalario de Toledo and Hospital Universitario 12 de Octubre (Madrid).

Craniopharyngiomas (CPs) are histologically benign tumors that are associated with high levels of morbidity. Two clinicopathological variants - adamantinomatous (ACP) and papillary (PCP) - have been described. They differ in their molecular features, whereby activating mutations in BRAF (V600E) and CTNNB1 genes characterize PCP and ACP, respectively. Recently, both variants have been shown to express elevated PD-L1 protein expression, but ACP also exhibited tumor cell-intrinsic PD-1 expression. In this study we analyze these molecular alterations in 52 cases with a long follow-up and examine their associations with immunohistochemical and clinical characteristics. ACPs comprise 73.1% of cases, while 21.2% are PCPs. Aberrant nuclear immunoreactivity for ß-catenin was observed in all ACPs. BRAF p.V600E mutations were observed in 90.9% of PCPs. Only one ACP case featured both alterations. Both types of CP exhibited strong nuclear staining for p63 with diffuse and basal distribution. ACP and PCP consistently expressed PD-L1, most in a substantial percentage of tumor cells, with a distinctive spatial distribution of expression in each subtype; only ACP demonstrated PD-1 expression. There was no evidence of differences in clinical prognosis between ACPs and PCPs. The identification of hallmark molecular signatures in the two CP variants is useful for sub-categorization in routine histopathology reporting. It is also pertinent to personalized therapy and for the development of improved non-invasive therapeutic strategies in this disease.

Co-occurrence of neurofibromatosis type 1 and optic nerve gliomas with autosomal dominant polycystic kidney disease type 2.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) and neurofibromatosis type 1 (NF1) are both autosomal dominant disorders with a high rate of novel mutations. However, the two disorders have distinct and well-delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and NF1 in a single individual have been reported, but the possible implications of this association are unknown. METHODS: We report an ADPKD male belonging to a family of several affected members in three generations associated with NF1 and optic pathway gliomas. The clinical diagnosis of ADPKD and NF1 was performed by several image techniques. RESULTS: Linkage analysis of ADPKD family was consistent to the PKD2 locus by a nonsense mutation, yielding a truncated polycystin-2 by means of next-generation sequencing. The diagnosis of NF1 was confirmed by mutational analysis of this gene showing a 4-bp deletion, resulting in a truncated neurofibromin, as well. The impact of this association was investigated by analyzing putative genetic interactions and by comparing the evolution of renal size and function in the proband with his older brother with ADPKD without NF1 and with ADPKD cohorts. CONCLUSION: Despite the presence of both conditions there was not additive effect of NF1 and PKD2 in terms of the severity of tumor development and/or ADPKD progression.

Satisfaction of patients and primary care professionals with a teleophthalmology-based screening programme for diabetic retinopathy in a rural area in Castilla y León, Spain.

INTRODUCTION: Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults in most developed countries. Early diagnosis and early treatment for retinopathy can reduce the incidence of severe loss of vision in a high percentage of sight-threatening DR. However, sight-threatening DR is asymptomatic in a high percentage of patients and no more than 50% of the diabetic patients are reviewed periodically in ophthalmology, mainly in rural areas. Telemedicine facilitates the exchange of information among professionals, reducing unnecessary journeys for patients who live in rural or remote areas. The survey of satisfaction is a highly useful quantitative instrument to obtain information directly from the users of a screening program. One aim of this study has been to determine the prevalence of DR in a sample of diabetic patients from a rural area of Spain and to classify DR patients according to the type and severity of this complication of the disease. The other main target was to evaluate the degree of satisfaction in both diabetic patients and professionals with a teleophthalmology-based screening program of DR. METHODS: A sample of 114 diabetic patients included in a new teleophthalmology program for the screening of DR in Castilla y León, Spain, were asked to take part in an in-person survey designed to evaluate the degree of satisfaction. This sample was obtained through a consecutive non-probability sampling technique, out of a total of 752 diabetic patients who underwent a retinography screening program in a distant rural healthcare center. The survey assessed aspects related to the information about the program the patients received, the organization of the center, the way the test was conducted and the reception of the results. All the included participants consented to participate in this study. Additionally, an anonymous survey was conducted via email. The sample was made up of 10 professionals responsible for taking the retinal images from the patients included in the study. This survey assessed their degree of satisfaction with their training, the way the test was carried out, the support from their managers and how this activity influenced their relationship with their patients. RESULTS: A high percentage of patients with DR in the study sample had a form of sight-threatening retinopathy (29.4%), which in this program is a criterion of referral to be assessed by an ophthalmologist. Of the surveyed patients, 93.8% scored eight points or higher for their degree of general satisfaction with the activity. All of them claimed they would prefer to continue their exploration at the healthcare center instead of going to the hospital. As regards the professionals, 70% scored eight points or more in terms of their degree of general satisfaction with the activity, whereas 20% scored between five and seven. One professional did not respond to the question. Finally, 90% stated that they would continue performing the activity, while the remaining 10% answered no. CONCLUSION: According to the high percentage of patients diagnosed with vision-threatening DR in this study, an early diagnosis of this complication of diabetes seems to be important. Teleophthalmology enhances patient accessibility to the healthcare system, making early diagnosis of DR easier, with a high degree of satisfaction among patients and healthcare professionals.

Frizzled 1 and Wnt1 as new potential therapeutic targets in the traumatically injured spinal cord.

Despite the experimental evidence pointing to a significant role of the Wnt family of proteins in physiological and pathological rodent spinal cord functioning, its potential relevance in the healthy and traumatically injured human spinal cord as well as its therapeutic potential in spinal cord injury (SCI) are still poorly understood. To get further insight into these interesting issues, we first demonstrated by quantitative Real-Time PCR and simple immunohistochemistry that detectable mRNA expression of most Wnt components, as well as protein expression of all known Wnt receptors, can be found in the healthy human spinal cord, supporting its potential involvement in human spinal cord physiology. Moreover, evaluation of Frizzled (Fz) 1 expression by double immunohistochemistry showed that its spatio-temporal and cellular expression pattern in the traumatically injured human spinal cord is equivalent to that observed in a clinically relevant model of rat SCI and suggests its potential involvement in SCI progression/outcome. Accordingly, we found that long-term lentiviral-mediated overexpression of the Fz1 ligand Wnt1 after rat SCI improves motor functional recovery, increases myelin preservation and neuronal survival, and reduces early astroglial reactivity and NG2+ cell accumulation, highlighting the therapeutic potential of Wnt1 in this neuropathological situation.

Spatio-temporal and Cellular Expression Patterns of PTK7 in the Healthy and Traumatically Injured Rat and Human Spinal Cord.

Despite the emerging role of protein tyrosine kinase 7 (PTK7) as a Wnt co-receptor and the relevant functions of the Wnt family of proteins in spinal cord injury (SCI), the potential involvement of PTK7 in SCI is currently unknown. As a first essential step to shed light on this issue, we evaluated the spatio-temporal and cellular expression patterns of PTK7 in healthy and traumatically injured rat and human spinal cords. In the uninjured rats, PTK7 expression was observed in the ependymal epithelium, endothelial cells, meningeal fibronectin-expressing cells, and specific axonal tracts, but not in microglia, astrocytes, neurons, oligodendrocytes, or NG2+ cells. After rat SCI, the mRNA expression of PTK7 was significantly increased, while its spatio-temporal and cellular protein expression patterns also suffered evident changes in the injured region. Briefly, the expression of PTK7 in the affected areas was observed in axons, reactive astrocytes, NG2+ and fibronectin-expressing cells, and in a subpopulation of reactive microglia/macrophages and blood vessels. Finally, in both healthy and traumatically injured human spinal cords, PTK7 expression pattern was similar to that observed in the rat, although some specific differences were found. In conclusion, we demonstrate for the first time that PTK7 is constitutively expressed in the healthy adult rat and human spinal cord and that its expression pattern clearly varied after rat and human SCI which, to our knowledge, constitutes the first experimental evidence pointing to the potential involvement of this co-receptor in physiological and pathological spinal cord functioning.

Evaluation of Neurosecretome from Mesenchymal Stem Cells Encapsulated in Silk Fibroin Hydrogels.

Physical and cognitive disabilities are hallmarks of a variety of neurological diseases. Stem cell-based therapies are promising solutions to neuroprotect and repair the injured brain and overcome the limited capacity of the central nervous system to recover from damage. It is widely accepted that most benefits of different exogenously transplanted stem cells rely on the secretion of different factors and biomolecules that modulate inflammation, cell death and repair processes in the damaged host tissue. However, few cells survive in cerebral tissue after transplantation, diminishing the therapeutic efficacy. As general rule, cell encapsulation in natural and artificial polymers increases the in vivo engraftment of the transplanted cells. However, we have ignored the consequences of such encapsulation on the secretory activity of these cells. In this study, we investigated the biological compatibility between silk fibroin hydrogels and stem cells of mesenchymal origin, a cell population that has gained increasing attention and popularity in regenerative medicine. Although the survival of mesenchymal stem cells was not affected inside hydrogels, this biomaterial format caused adhesion and proliferation deficits and impaired secretion of several angiogenic, chemoattractant and neurogenic factors while concurrently potentiating the anti-inflammatory capacity of this cell population through a massive release of TGF-Beta-1. Our results set a milestone for the exploration of engineering polymers to modulate the secretory activity of stem cell-based therapies for neurological disorders.

Aislamiento de Pseudomonas aeruginosa en serpientes ecuatorianas y su potencial repercusión en accidentes ofídicos / Isolation of pseudomonas aeruginosa in ecuadorian snakes and their potential impact on snakebite accidents

Debido a la alta incidencia de mordeduras de serpientes, la Organización Mundial de la Salud (OMS) ha catalogado estos accidentes como una de las enfermedades tropicales desatendidas más importantes del planeta. En Ecuador los accidentes ocasionados por mordeduras de serpientes representan un alto riesgo para la vida. Este país registra un promedio de 1.657 casos de mordeduras de serpientes al año (considerando reportes de CIVE MSP desde el 2014 al 2016). Las infecciones secundarias son una de las principales complicaciones en accidentes ofídicos. Pseudomonas aeruginosa es un patógeno oportunista, gramnegativo, cosmopolita y ampliamente vinculado con infecciones graves en pacientes hospitalizados; en este contexto se considera como factor de riesgo la disrupción de la piel causada por mordeduras de serpientes y la afectación del sistema inmunitario a causa del envenenamiento ofídico. El objetivo de la investigación fue determinar la presencia de P. aeruginosa en la cavidad bucal de serpientes ecuatorianas mantenidas en cautiverio con la finalidad de evidenciar un indicador de potenciales infecciones secundarias por estemicroorganismo. El estudio se realizó en 136 serpientes de diferentes géneros y especies, de las cuales el 33,09 % resultó positivo a P. aeruginosa. El muestreo se realizó por hisopado directo, en la parte superior e inferior de la cavidad bucal de las serpientes. Las muestras fueron cultivadas en agar Cetrimide. El estudio se apoyó en las técnicas de tinción de Gram y pruebas bioquímicas confirmatorias. Los estudios de sensibilidad evidenciaron que el antibiótico más activo frente a P. aeruginosa fue el imipenem, demostrando variabilidad en resistencia a los otros antibióticos.

Due to the high incidence of snake bites, WHO has classified these accidents as one of the most important neglected tropical diseases on the planet. In Ecuador, accidents caused by snake bites represent a high risk for life. This country records an average of 1657 cases of snake bites per year (considering reports from CIVE MSP from 2014 to 2016). Secondary infections are one of the major complications in ophidian accidents. Pseudomonas aeruginosa is an opportunistic, gram-negative, cosmopolitan pathogen that is widely associated with severe infections in hospitalized patients; in this context, disruption of the skin caused by snake bites and impingement of the immune system due to poisoning is considered a risk factor. The objective of the investigation was to determine the presence of P. aeruginosa in the oral cavity of Ecuadorian snakes kept in captivity in order to evidence an indicator of potential secondary infections by this microorganism. The study wason 136 snakes of different genera and species, of which 33,09 % were positive for P. aeruginosa. Sampling was performed bydirect swabbing, at the top and bottom of the buccal cavity of the snakes. The samples were cultured on Cetrimide agar. The study was based on Gram staining techniques and confirmatory biochemical tests. Sensitivity studies showed that the most active antibiotic against P. aeruginosa was imipenem, demonstrating variability in resistance to other antibiotics.

Obstetric care navigation: a new approach to promote respectful maternity care and overcome barriers to safe motherhood.

BACKGROUND: Disrespectful and abusive maternity care is a common and pervasive problem that disproportionately impacts marginalized women. By making mothers less likely to agree to facility-based delivery, it contributes to the unacceptably high rates of maternal mortality in low- and middle-income countries. Few programmatic approaches have been proposed to address disrespectful and abusive maternity care. OBSTETRIC CARE NAVIGATION: Care navigation was pioneered by the field of oncology to improve health outcomes of vulnerable populations and promote patient autonomy by providing linkages across a fragmented care continuum. Here we describe the novel application of the care navigation model to emergency obstetric referrals to hospitals for complicated home births in rural Guatemala. Care navigators offer women accompaniment and labor support intended to improve the care experience-for both patients and providers-and to decrease opposition to hospital-level obstetric care. Specific roles include deflecting mistreatment from hospital staff, improving provider communication through language and cultural interpretation, advocating for patients' right to informed consent, and protecting patients' dignity during the birthing process. Care navigators are specifically chosen and trained to gain the trust and respect of patients, traditional midwives, and biomedical providers. We describe an ongoing obstetric care navigator pilot program employing rapid-cycle quality improvement methods to quickly identify implementation successes and failures. This approach empowers frontline health workers to problem solve in real time and ensures the program is highly adaptable to local needs. CONCLUSION: Care navigation is a promising strategy to overcome the "humanistic barrier" to hospital delivery by mitigating disrespectful and abusive care. It offers a demand-side approach to undignified obstetric care that empowers the communities most impacted by the problem to lead the response. Results from an ongoing pilot program of obstetric care navigation will provide valuable feedback from patients on the impact of this approach and implementation lessons to facilitate replication in other settings.

Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib.

Sunitinib is the currently standard treatment for metastatic renal cell carcinoma (mRCC). Multiple candidate predictive biomarkers for sunitinib response have been evaluated but none of them has been implemented in the clinic yet. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) in genes linked to mode of action of sunitinib and immune response as biomarkers for mRCC. This is a multicenter, prospective and observational study involving 20 hospitals. Seventy-five mRCC patients treated with sunitinib as first line were used to assess the impact of 63 SNPs in 31 candidate genes on clinical outcome. rs2243250 (IL4) and rs5275 (PTGS2) were found to be significantly associated with shorter cancer-specific survival (CSS). Moreover, allele C (rs5275) was associated with higher PTGS2 expression level confirming its functional role. Combination of rs5275 and rs7651265 or rs2243250 for progression free survival (PFS) or CSS, respectively, was a more valuable predictive biomarker remaining significant after correction for multiple testing. It is the first time that association of rs5275 with survival in mRCC patients is described. Two-SNP models containing this functional variant may serve as more predictive biomarkers for sunitinib and could suppose a clinically relevant tool to improve the mRCC patient management.