Implementación del diagnóstico molecular del VPH: experiencia chilena en curso / Molecular diagnosis of human papillomavirus infection: the Chilean experience

Cervical Cancer (CaCu) has a heterogeneous epidemiological behavior throughout the planet, depending on regional socioeconomic development level. Some developed countries predict a potential eradication of this cancer in the next 100 years, while in Chile it still constitutes a pending challenge. Incidence rates show a slow but sustained downward prob, however, mortality has continued to fluctuate between 500-600 cases per year. A few years ago, vaccination against Human Papillomavirus (HPV), the main causal agent for this tumor, was consolidated as a public policy, both in girls and in boys. However, the technological leap in the screening prob was pending, from cytology to molecular diagnosis of the agent (HPV). In this report, we update our most recent data (2018) regarding CaCu mortality, then review global guidelines and experiences in HPV screening. Finally, we offer an account of the strategies that our health system is promoting to address the screening of the disease and whose molecular approach generates the widest worldwide scientific consensus. We also recognize the main barriers and future challenges, which, if overcome, would allow us to be in line with the mandate of WHO to control this women's health problema.

[Molecular diagnosis of human papillomavirus infection. The Chilean experience]. / Implementación del diagnóstico molecular del VPH: experiencia chilena en curso.

Cervical Cancer (CaCu) has a heterogeneous epidemiological behavior throughout the planet, depending on regional socioeconomic development level. Some developed countries predict a potential eradication of this cancer in the next 100 years, while in Chile it still constitutes a pending challenge. Incidence rates show a slow but sustained downward prob, however, mortality has continued to fluctuate between 500-600 cases per year. A few years ago, vaccination against Human Papillomavirus (HPV), the main causal agent for this tumor, was consolidated as a public policy, both in girls and in boys. However, the technological leap in the screening prob was pending, from cytology to molecular diagnosis of the agent (HPV). In this report, we update our most recent data (2018) regarding CaCu mortality, then review global guidelines and experiences in HPV screening. Finally, we offer an account of the strategies that our health system is promoting to address the screening of the disease and whose molecular approach generates the widest worldwide scientific consensus. We also recognize the main barriers and future challenges, which, if overcome, would allow us to be in line with the mandate of WHO to control this women's health problema.

Analysis of gluten immunogenic peptides in feces to assess adherence to the gluten-free diet in pediatric celiac patients.

PURPOSE: In celiac disease (CD) there is a need for precise and non-invasive tools to assess dietary compliance to the gluten-free diet (GFD). Our aim is to evaluate the efficacy of the detection of gluten immunogenic peptides (GIP) in feces, to monitor in real life, the adherence to GFD in pediatric patients with CD. METHODS: A cross-sectional, prospective study was conducted. Fecal samples from CD children were analyzed by a rapid immunochromatographic (IC) test and by an ELISA method, both based on the antigliadin 33-mer monoclonal antibody. RESULTS: Group 1 comprises 43 children on a GFD. According to the food records (FR), 39/43 patients were compliant with the GFD and gluten consumption was recorded in 4. GIP were detected in 15/43 individuals by the ELISA method and also in 7 by IC strips. Group 2: comprise 18 children at CD diagnosis; GIP levels decreased over time (p < 0.001) in a non-linear way (p = 0.028) after starting a GFD and were below the detection limit on the third day in most individuals. CONCLUSION: GIP were detected, both by ELISA and by IC strips, in CD patients on a GFD, in which no consumption of gluten had been registered on the FR, confirming GIP detection to be superior to FR discovering involuntary transgressions. Despite a positive correlation between the amount of gluten intake and the concentration of GIP in feces, the interindividual variations observed suggest gastrointestinal factors influencing GIP recovery need to be further investigated.

Management of non-invasive tumours, benign tumours and breast cancer during the COVID-19 pandemic: recommendations based on a Latin American survey.

INTRODUCTION: The COVID-19 pandemic has changed health systems across the world, both in general hospitals and in oncology institutes or centres.For cancer specialists, particularly breast cancer (BC), the COVID-19 pandemic represents a combination of challenges since the hospital resources and staff have become more limited; this has obliged oncology specialists to seek a consensus and establish which patients with BC require more urgent attention and which patients can wait until there is a better control of this pandemic. The health system in Latin America has some special characteristics; in some of the countries, there are shortages which limit access to several specialities (surgery, clinical oncology and radiotherapy) in some regions. OBJECTIVE: After a systematic review of the most recent literature regarding the management of BC during the COVID-19 pandemic, the main objective is to understand the position of the different Latin American Societies of Mastology in terms of available alternatives for the treatment of BC. METHODS: After carrying out a comprehensive and exhaustive search of the most recent guides on the management of BC during the COVID-19 pandemic, the board members of the Latin American Federation of Mastology invited, via email, different specialists, all experts in BC care, to complete an anonymous survey online.The survey was distributed between 30 and 10 May 2020. The survey included 27 questions on four topics: demographic information, consultations, imaging and treatment of BC.The questionnaire was sent and then distributed to various health specialists including breast surgeons, clinical oncologists, radiation oncologists and radiologists via the Presidents of the different Latin American Societies of Mastology in 18 countries. The results are summarised as tallies based on the number of responses to each question. RESULTS: A total of 499 responses were received. The majority of the respondents were males (275 (55.11%)); 290 participants were over 45 years (58.11%).The questionnaire presented those surveyed with three possible answers (agree, disagree and neither agree nor disagree). The results reflect that there was consensus in the majority of situations presented. Only seven questions revealed disagreement among those responding. The results are presented as recommendations. CONCLUSION: The management of patients with BC presents unique challenges during the current world health situation produced by COVID-19 pandemic. Breast care specialists (surgical oncologists, breast care clinicians, clinical oncologists, radiation oncologists and radiologists) from 18 countries in Central and South America submitted through their responses and recommendations for the treatment of BC during the COVID-19 pandemic.

Desafío hospitalario: experiencia de un equipo de ginecología en el manejo integral de pacientes COVID 19 / A hospital challenge: experience of a gynecology team in the comprehensive management of patients COVID 19

INTRODUCCIÓN: La infección por el coronavirus SARS-CoV2 (COVID 19), causal de la pandemia actual, ha significado a nivel mundial la hospitalización simultánea de múltiples pacientes poniendo a prueba la infraestructura hospitalaria y la capacidad de reacción del personal de salud. Una de las estrategias para el manejo es la reconversión de camas y servicios clínicos. OBJETIVOS: presentar experiencia de un equipo ginecológico en el manejo integral de pacientes no gineco-obstétricas con COVID 19, durante el mes de junio de 2020 en un hospital público de la Región Metropolitana. MÉTODOS: Estudio de corte transversal observacional, descriptivo. Se consideró el total de pacientes adultos hombres y mujeres sin patología gineco-obstétrica con COVID 19 ingresados al puerperio del Hospital Santiago Oriente, obteniéndose datos clínicos y demográficos a través del registro interno de la unidad y del sistema de información de red asistencial. RESULTADOS: Ingresaron 82 pacientes, 32 mujeres y 50 hombres, promedio de edad 64. El promedio de días de hospitalización fue 5, con diagnóstico de ingreso principal neumonía viral por COVID-19. Las comorbilidades frecuentes fueron hipertensión arterial sistémica y diabetes mellitus. La complicación más frecuente fue el tromboembolismo pulmonar agudo. Hubo una alta cobertura de entrega de información vía telefónica a familiares. De los 82 ingresos, 54 pacientes egresaron a su domicilio. El resto a otras unidades dentro de la institución, centros de menor complejidad o residencias sanitarias. Una paciente sexo femenino de 75 años fallece a causa de descompensación de patologias de base secundario a neumonia por Staphylococus aereus. En ella, se descarta la infección por COVID 19 dado tres exámenes por reacción de polimerasa en cadena negativos realizado antes y durante su hospitalización. CONCLUSIONES: Esta experiencia constituyó un desafío para todo el equipo de salud gineco-obstétrico, considerando que nos enfrentamos a otro tipo de pacientes y a una patología nueva. Los resultados médicos son promisorios, la experiencia humana y sentido de trabajo en equipo fue extraordinario.

INTRODUCTION: The infection by the SARS-CoV2 coronavirus (COVID 19), the cause of the current pandemic we are experiencing, has meant the simultaneous hospitalization of many patients worldwide, putting the hospital infrastructure and the reaction capacity of health personnel to the test. One of the management strategies is the reconversion of clinical services. OBJECTIVES: present the experience of a gynecological team in the comprehensive management of non-gyneco-obstetric patients with COVID 19, during the month of June 2020 in a public hospital in the Metropolitan Region. METHODS: descriptive, observational cross-sectional study. The total number of patients admitted to the ex-puerperium of the Santiago Oriente Hospital was considered, obtaining clinical and demographic data through the unit's internal registry and the healthcare network information system. RESULTS: 82 patients were admitted, 32 women and 50 men, average age 64. The average number of days of hospitalization was 5, with the main admission diagnosis being viral pneumonia due to COVID-19. Frequent comorbidities were systemic arterial hypertension and diabetes mellitus. The most frequent complication was acute pulmonary thromboembolism. There was a high coverage of the delivery of information via telephone to relatives. Of the 82 admissions, 54 patients were discharged home and the rest to other units within the institution, less complex centers or health residences. One 75 years old female patient dies from concomitant pathologies, and she wasn't positive for COVID-19. CONCLUSIONS: This experience was a challenge for the entire gynecological-obstetric health team, considering that we are facing other types of patients and a new pathology. The medical results are promising, the human experience and sense of teamwork was extraordinary.

Clinical validation of an evidence-based method to adjust Pancreatic Enzyme Replacement Therapy through a prospective interventional study in paediatric patients with Cystic Fibrosis.

BACKGROUND: A method to adjust Pancreatic Enzyme Replacement Therapy in Cystic Fibrosis is not currently available. OBJECTIVES: To assess the in vivo efficacy of a method to adjust the dose of enzymatic supplement in CF extrapolated from previous in vitro digestion studies (theoretical optimal dose, TOD). Secondly, to assess how individual patient characteristics influence the expected coefficient of fat absorption (CFA) and thus to identify an individual correction factor to improve TOD. METHODS: A prospective interventional study in 43 paediatric patients with CF from 5 European centres. They followed a 24h fixed diet with the theoretical optimal dose for each meal. Faecal collection was carried out between colorimetric markers in order to include all the faeces corresponding to the fixed diet. Beta regression models were applied to assess the associations of individual patient characteristics with the CFA. RESULTS: Median CFA was 90% (84, 94% 1st, 3rd Q.) with no significant differences among centres. Intestinal transit time was positively associated with CFA (p = 0.007), but no statistical associations were found with and age, gender, phenotype or BMI. Regression model showed no improvement of the in vitro predicted theoretical optimal dose when taking individual patient characteristics into account. CONCLUSION: Strict adherence to the theoretical optimal dose of enzymatic supplement for a prescribed meal, led to median CFA levels at the clinical target of 90% with a low variability between patients. The proposed method can be considered as a first approach for an evidence-based method in PERT dosing based on food characteristics. Results have to be confirmed in free dietary settings.

Ten years of follow-up of the Spanish cohort of the European PreventCD study: the lessons learned.

AIM: to evaluate the influence of gluten consumption on celiac disease development and to describe its natural history in the Spanish cohort of the European PreventCD study. METHODS: prospective multi-center double blind study of 225 children that were followed up from birth. All cases were HLA-DQ2/HLA-DQ8 positive with a 1st degree relative with celiac disease and were followed up in three centers from Madrid, Reus and Valencia. Gluten intake was determined between four and ten months according to the protocol. Gluten intake was ad libitum between eleven and 36 months and was prospectively quantified by means of dietary records. Clinical visits and specific antibody analysis for celiac disease were performed periodically. RESULTS: twenty-six cases were diagnosed, all had a positive biopsy and serology; 21 had gastrointestinal symptoms and five were asymptomatic. In addition, 2,565 food records were analyzed and statistically significant differences (p < 0.001) were found with regard to gluten consumption among the three centers, although not between celiac and non-celiac children (p = 0.025). The HLA-DQ2.5/DQ2.5 and DQ2.5/DQ2.2 genotypes had a relative risk of 4.7 (95% CI: 0.80-27.55; p = 0.08), which was higher than for the rest of genotypes. Female gender also had a relative risk that was five times higher than that for males. CONCLUSIONS: the amount of gluten intake between 11 and 36 months or the duration of breast feeding were not risk factors for the development of CD in the Spanish population. The HLA genotype and gender were the most relevant associated factors. In this at-risk group, the disease presented before two years of age in the majority of the cases with a weak clinical expression.

Malformación arteriovenosa cerebelosa en paciente pediátrico. Presentación de autopsia / Cerebellar arteriovenous malformation in a pediatric patient. Autopsy presentation

Se presenta un paciente masculino de 6 años de edad, quien consultó por cefalea de inicio súbito posterior a un acceso de tos y asociado con síntomas comportamentales. Comentan los padres que en los dos días previos se quejó de odinofagia y tos seca ocasional, sin alteraciones al examen físico de ingreso ni antecedentes clínicos de importancia con posterior fallecimiento. A continuación se presentan los hallazgos de autopsia tanto macroscópica como microscópicamente y una breve discusión teórica del tema.

The current article present a 6-year-old male patient, who consults for sudden onset headache after coughing with behavioral symptoms associated with normal physical exam at admission and no important clinical record, subsequent death without identifiable cause. The parents report a previous two-day symptoms of odynophagia and occasional dry cough. Below are the findings of autopsy both macroscopically and microscopically and a brief theoretical discussion.

Innovative approach for self-management and social welfare of children with cystic fibrosis in Europe: development, validation and implementation of an mHealth tool (MyCyFAPP).

INTRODUCTION: For the optimal management of children with cystic fibrosis, there are currently no efficient tools for the precise adjustment of pancreatic enzyme replacement therapy, either for advice on appropriate dietary intake or for achieving an optimal nutrition status. Therefore, we aim to develop a mobile application that ensures a successful nutritional therapy in children with cystic fibrosis. METHODS AND ANALYSIS: A multidisciplinary team of 12 partners coordinate their efforts in 9 work packages that cover the entire so-called 'from laboratory to market' approach by means of an original and innovative co-design process. A cohort of 200 patients with cystic fibrosis aged 1-17 years are enrolled. We will develop an innovative, clinically tested mobile health application for patients and health professionals involved in cystic fibrosis management. The mobile application integrates the research knowledge and innovative tools for maximising self-management with the aim of leading to a better nutritional status, quality of life and disease prognosis. Bringing together different and complementary areas of knowledge is fundamental for tackling complex challenges in disease treatment, such as optimal nutrition and pancreatic enzyme replacement therapy in cystic fibrosis. Patients are expected to benefit the most from the outcomes of this innovative project. ETHICS AND DISSEMINATION: The project is approved by the Ethics Committee of the coordinating organisation, Hospital Universitari La Fe (Ref: 2014/0484). Scientific findings will be disseminated via journals and conferences addressed to clinicians, food scientists, information and communications technology experts and patients. The specific dissemination working group within the project will address the wide audience communication through the website (http://www.mycyfapp.eu), the social networks and the newsletter.

Randomized feeding intervention in infants at high risk for celiac disease.

BACKGROUND: A window of opportunity has been suggested for reducing the risk of celiac disease by introducing gluten to infants at 4 to 6 months of age. METHODS: We performed a multicenter, randomized, double-blind, placebo-controlled dietary-intervention study involving 944 children who were positive for HLA-DQ2 or HLA-DQ8 and had at least one first-degree relative with celiac disease. From 16 to 24 weeks of age, 475 participants received 100 mg of immunologically active gluten daily, and 469 received placebo. Anti-transglutaminase type 2 and antigliadin antibodies were periodically measured. The primary outcome was the frequency of biopsy-confirmed celiac disease at 3 years of age. RESULTS: Celiac disease was confirmed by means of biopsies in 77 children. To avoid underestimation of the frequency of celiac disease, 3 additional children who received a diagnosis of celiac disease according to the 2012 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria (without having undergone biopsies) were included in the analyses (80 children; median age, 2.8 years; 59% were girls). The cumulative incidence of celiac disease among patients 3 years of age was 5.2% (95% confidence interval [CI], 3.6 to 6.8), with similar rates in the gluten group and the placebo group (5.9% [95% CI, 3.7 to 8.1] and 4.5% [95% CI, 2.5 to 6.5], respectively; hazard ratio in the gluten group, 1.23; 95% CI, 0.79 to 1.91). Rates of elevated levels of anti-transglutaminase type 2 and antigliadin antibodies were also similar in the two study groups (7.0% [95% CI, 4.7 to 9.4] in the gluten group and 5.7% [95% CI, 3.5 to 7.9] in the placebo group; hazard ratio, 1.14; 95% CI, 0.76 to 1.73). Breast-feeding, regardless of whether it was exclusive or whether it was ongoing during gluten introduction, did not significantly influence the development of celiac disease or the effect of the intervention. CONCLUSIONS: As compared with placebo, the introduction of small quantities of gluten at 16 to 24 weeks of age did not reduce the risk of celiac disease by 3 years of age in this group of high-risk children. (Funded by the European Commission and others; PreventCD Current Controlled Trials number, ISRCTN74582487.).

Soluble factors derived from tumor mammary cell lines induce a stromal mammary adipose reversion in human and mice adipose cells. Possible role of TGF-beta1 and TNF-alpha.

In carcinomas such as those of breast, pancreas, stomach, and colon, cancer cells support the expansion of molecular and cellular stroma in a phenomenon termed desmoplasia, which is characterized by a strong fibrotic response. In the case of breast tissue, in which stroma is mainly a fatty tissue, this response presumably occurs at the expense of the adipose cells, the most abundant stromal phenotype, generating a tumoral fibrous structure rich in fibroblast-like cells. In this study, we aimed to determine the cellular mechanisms by which factors present in the media conditioned by MDA-MB-231 and MCF-7 human breast cancer cell lines induce a reversion of adipose cells to a fibroblastic phenotype. We demonstrated that soluble factors generated by these cell lines stimulated the reversion of mammary adipose phenotype evaluated as intracellular lipid content and expression of C/EBP alpha and PPAR gamma. We also demonstrated that exogenous TGF-beta 1 and TNF-alpha exerts a similar function. The participation of both growth factors, components of media conditioned by tumoral mammary cells, on the expression and nuclear translocation of C/EBP alpha and PPAR gamma was tested in 3T3-L1 cells by interfering with the inhibitory effects of media with agents that block the TGF-beta 1 and TNF-alpha activity. These results allow us to postulate that TGF-beta 1 and TNF-alpha present in this media are in part responsible for this phenotypic reversion.

Disfagia orofaríngea en el perro: reporte de dos casos / Oropharyngeal dysphagia in dog: report of cases

Se describen dos casos clínicos, que fueron presentados a consulta en el Hospital veterinario Diego Villegas de la Universidad de caldas, con un cuadro neumónico grave; luego del examen físico y de realizar diversas pruebas, se concluyo que los diagnósticos más probables incluían acalasia cricofaríngea (AC) y disfagia faríngea (DF). Se discuten las alternativas terapéuticas y la evolución clínica de los pacientes. Se menciona el ensayo terapéutico realizado en uno de los pacientes de acuerdo con lo sugerido por la literatura....

[Cost-benefit in the study of the dissemination of stage I and II in breast cancer]. / Costo beneficio del estudio de diseminación en estadios I y II del cáncer de mama.

BACKGROUND: Chest X ray, abdominal ultrasound and bone scintigraphy are usually requested to study a possible dissemination of breast carcinoma. AIM: To study the yield and costs of these exams in the study of dissemination of stage I and II breast carcinoma. MATERIAL AND METHODS: A retrospective analysis of patients operated for a breast carcinoma in a public surgical service. A chest X ray, abdominal ultrasound and bone scintigraphy was requested to all patients in the immediate postoperative period. Age, stage according to pathological TNM and costs per patient were registered. RESULTS: Of 210 women operated, 40 were in stage I (19%) and 85 in stage II (41%). Dissemination study was negative in all stage I patients and in all but two patients in stage II. The yield for detection of distant metastases in these patients was 0.9% for chest X ray, 0% for abdominal ultrasound and 0.9% for bone scintigraphy. The total cost of the study, in Chilean pesos, was $10,369,620 in a public hospital and $16,535,400 in a private clinic. DISCUSSION: Additional exams to detect distant metastases in early stages of breast carcinoma have a low yield and high costs.

Adhesion of B cell lines to endothelial cells from human lymphoid tissue modulates tyrosine phosphorylation and endothelial cell activation.

Through the production of cytokines and growth factors the endothelium of secondary lymphoid organs plays a crucial role in controlling lymphocyte migration to the lymphoid microenvironment, an essential step in the initiation of the immune response. Here we demonstrate that direct contact of B cell lines with tonsil-derived human endothelial cells resulted in changes in the phosphorylation state of endothelial cells, causing their functional activation. We found a rapid (<15-s) and transient dephosphorylation, followed by a rapid rephosphorylation of tyrosine residues of the focal adhesion kinase, paxillin, and ERK2. Maximal rephosphorylation occurred after 15-30 min of B cell contact. Preincubation of lymphoid B cells with an adhesion-blocking Ab directed against alpha(4)beta(1) integrin abrogated adhesion-mediated changes of endothelial cell tyrosine phosphorylation, suggesting that cell contact was essential. Similar patterns of tyrosine phosphorylation, but with slightly different kinetics were induced after cross-linking of beta(1) integrin or CD40 on endothelial cells. Functional activation of endothelial cells by B cell adhesion was confirmed by the production of IL-6, IL-8, monocyte chemoattractant protein-1, M-CSF, and macrophage inflammatory protein-1beta mRNA. However, direct cross-linking of beta(1) integrin and CD40 failed to accomplish the same functional activation. These data indicate that direct contact of lymphoid B cells with the endothelium from lymphoid tissue induce endothelial cell signaling, resulting in chemokine and cytokine production. This phenomenon may provide a mechanism for the remodeling of the endothelium from lymphoid tissues, thus contributing to the free migration of lymphocytes and other cells into the lymphoid organs.

Derivación de la patología mamaria desde la atención primaria a la terciaria: experiencia con un consultorio / Breast pathology derivation from primary care to tertiary care: experience in a public clinic

El objetivo de este estudio es evaluar la comunicación entre un consultorio periférico y la atención terciaria y ver cómo influye esto en el tiempo de derivación y resolución del problema del paciente. Desde enero de 1999 a junio de 2001, se derivaron desde el consultorio de La Reina al equipo de Cirugía Mamaria del Servicio de Cirugía del Hospital del Salvador 62 pacientes con patología mamaria benigna y maligna, de las cuales consultaron finalmente 49. Todas las pacientes fueron derivadas por el mismo médico con el cual nuestro equipo tiene una fluida relación. Las derivaciones se realizaron mediante interconsulta y en los casos de sospecha de neoplasia el médico del consultorio informó, además, por vía telefónica. El poco tiempo de espera de estas pacientes para ser atendidas en el hospital (4 días) y para cirugía (20 días en los carcinomas), se explica por la buena comunicación con el médico del consultorio, lo que permita una expedita atención y por el conocimiento de éste de la patología mamaria