Efficacy and safety of withholding antimicrobial therapy in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.

OBJECTIVES: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection (RTI). METHODS: Prospective, multicenter, non-inferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus (RV), negative for a bacterial pathogen and had a favorable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with uneventful resolution, whereas the secondary endpoints were days of fever/hospitalization, requirement of antimicrobial treatment readministration, sepsis, pediatric intensive care unit (PICU) admission and death. RESULTS: A total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a RV as a unique identified microorganism, of which 139 had a favorable evolution at 48-72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3-6) versus 3 (IQR 3-6) days (p<0.001), with similar frequency of uneventful resolution (66/70 (94%) and 66/69 (96%), RR 1.01, (95% CI 0.93-1.09), absolute risk difference 0.01, (95% CI -0.05-0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, PICU admission or death were reported. CONCLUSIONS: We validated the strategy of withdrawal antimicrobial therapy in children with FN and viral RTI, based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance.

Características operativas de la ecografía en el diagnóstico del Síndrome de Sjögren / Operational characteristics of ultrasound in the diagnosis of Sjögren's syndrome

Antecedentes y objetivo: Determinar las características operativas de la ecografía de glándula salival (EGS) en el diagnóstico del síndrome de Sjögren (SS) en una población de pacientes colombianos con síntomas secos. Materiales y métodos: Estudio de pruebas diagnósticas en pacientes con síntomas secos que asistieron a la consulta de reumatología (2018-2020). Se obtuvieron datos sociodemográficos y clínicos a través de una encuesta, pruebas paraclínicas, oftalmológicas, biopsia de glándula salival menor, flujo salival no estimulado y EGS (puntuación 0-6 basada en De Vita). Se calcularon la sensibilidad, la especificidad y los valores predictivos positivo (VPP) y negativo (VPN) (Stata 15®). Se desarrolló la curva de características operativas del receptor (COR). Resultados: Se incluyó a 102 pacientes (34 con SS y 68 sin SS), edad media ± desviación estándar de 55,69 ± 11,93 años, 94% mujeres. La ecografía positiva (puntuación de 2 o más) fue más frecuente en el grupo de SS, (70,6% vs. 22,1%, p < 0,0001). La sensibilidad fue igual para el grado 2 y 3 (70,59%), con una especificidad mayor (89,71%) para el grado 3 (VPP 77,42% VPN 85,92). La curva COR a partir de la sumatoria de las glándulas por medio de ecografía, fue mejor que las de las glándulas independientes. La curva COR de la ecografía presentó una mayor área bajo la curva (0,72 [0,61-0,82]) que la del análisis histológico (puntuación por focos) (0,68 [0,59-0,78]), p = 0,0252. Conclusión: La EGS es un método útil y confiable para la clasificación del SS. Se podría plantear su uso futuro dentro de los criterios clasificatorios del SS.(AU)

Background and objective: To determine the operational characteristics of salivary gland ultrasound (SGU) in the diagnosis of Sjögren's syndrome (SS) in a population of colombian patients with dry symptoms. Materials and methods: Study of diagnostic tests in patients with dry symptoms who consecutively attended the rheumatology consultation (2018-2020). Sociodemographic and clinical data were obtained through a survey, paraclinical and ophthalmological tests, minor salivary gland biopsy, unstimulated salivary flow and SGU (score 0-6 based on De Vita) were done. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values (Stata 15®) were calculated. The receiver operating characteristics (ROC) curve was developed. Results: 102 patients were included (34 SS and 68 non-SS), mean age 55.69 (± 11.93) years, 94% women. Positive ultrasound (score of 2 or more) was more frequent in the SS group, (70.6% vs. 22.1%, P<.0001). The sensitivity was the same for grade 2 and 3 (70.59%), with a higher specificity (89.71%) for grade 3 (PPV 77.42% NPV 85.92). The ROC curve from the sum of the glands by means of ultrasound was better than those of the independent glands. The ROC curve of the ultrasound presented a greater area under the curve (0.72 [0.61-0.82]) than that of the histological analysis (focus score) (0.68 [0.59-0.78]), P=.0252. Conclusion: Salivary gland ultrasound is a useful and reliable method for the classification of SS. Its use could be considered in the future within the SS classification criteria.

Operational characteristics of ultrasound in the diagnosis of Sjögren's syndrome.

BACKGROUND AND OBJECTIVE: To determine the operational characteristics of salivary gland ultrasound (SGU) in the diagnosis of Sjögren's syndrome (SS) in a population of colombian patients with dry symptoms. MATERIALS AND METHODS: Study of diagnostic tests in patients with dry symptoms who consecutively attended the rheumatology consultation (2018-2020). Sociodemographic and clinical data were obtained through a survey, paraclinical and ophthalmological tests, minor salivary gland biopsy, unstimulated salivary flow and SGU (score 0-6 based on De Vita) were done. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values (Stata 15®) were calculated. The receiver operating characteristics (ROC) curve was developed. RESULTS: 102 patients were included (34 SS and 68 non-SS), mean age 55.69 (±11.93) years, 94% women. Positive ultrasound (score of 2 or more) was more frequent in the SS group, (70.6% vs. 22.1%, P<0.0001). The sensitivity was the same for grade 2 and 3 (70.59%), with a higher specificity (89.71%) for grade 3 (PPV 77.42% NPV 85.92). The ROC curve from the sum of the glands by means of ultrasound was better than those of the independent glands. The ROC curve of the ultrasound presented a greater area under the curve (0.72 [0.61-0.82]) than that of the histological analysis (focus score) (0.68 [0.59-0.78]), P=0.0252. CONCLUSION: Salivary gland ultrasound is a useful and reliable method for the classification of SS. Its use could be considered in the future within the SS classification criteria.

Risk scores' performance and their impact on operative decision-making in left-sided endocarditis: a cohort study.

The accuracy of contemporary risk scores in predicting perioperative mortality in infective endocarditis (IE) remains controversial. The aim is to evaluate the performance of existent mortality risk scores for cardiovascular surgery in IE and the impact on operability at high-risk thresholds. A single-center retrospective review of adult patients diagnosed with acute left-sided IE undergoing surgery from May 2014 to August 2019 (n = 142) was done. Individualized risk calculation was obtained according to the available mortality risk scores: EuroScore I and II, PALSUSE, Risk-E, Costa, De Feo-Cotrufo, AEPEI, STS-risk, STS-IE, APORTEI, and ICE-PCS scores. A cross-validation analysis was performed on the score with the best area under the curve (AUC). The 30-day survival was 96.5% (95%CI 91-98%). The score with worse area under the curve (AUC = 0.6) was the STS-IE score, while the higher was for the RISK-E score (AUC = 0.89). The AUC of the majority of risk scores suggested acceptable performance; however, statistically significant differences in expected versus observed mortalities were common. The cross-validation analysis showed that a large number of survivors (> 75%) would not have been operated if arbitrary high-risk threshold estimates had been used to deny surgery. The observed mortality in our cohort is significantly lower than is predicted by contemporary risk scores. Despite the reasonable numeric performance of the analyzed scores, their utility in judging the operability of a given patient remains questionable, as demonstrated in the cross-validation analysis. Future guidelines may advise that denial of surgery should only follow a highly experienced Endocarditis Team evaluation.

Neuroleptic malignant syndrome in a postoperative patient: A case report.

Neuroleptic malignant syndrome is a rare medical emergency associated with the use of antipsychotics and other antidopaminergic drugs. There is no specific test, and diagnosis is based on high clinical suspicion and good differential diagnosis. A clinical picture consistent with hyperthermia, muscle rigidity, altered level of consciousness, together with signs of rhabdomyolysis in analytical studies and a history of taking neuroleptic drugs are the key elements in the detection of this entity. Due to its low incidence and potential mortality, it is essential to publish case reports of neuroleptic malignant syndrome in order to raise awareness of this entity and facilitate diagnostic suspicion when encountering a patient with compatible symptoms. The following is the case of a 79 year old patient with chronic alcohol consumption as the only history of interest, who was given a single dose of haloperidol after an episode of delirium in the postoperative period of conventional trauma surgery. She subsequently developed a picture of progressive deterioration of the level of consciousness, diaphoresis, generalized muscle rigidity, hyperthermia, together with severe metabolic acidosis, hyperlacticaemia, rhabdomyolysis, hypertransaminasemia and hypocalcemia. After ruling out other entities compatible with the clinical picture, neuroleptic malignant syndrome was given as the main diagnostic hypothesis. Diagnosis was confirmed after clinical and analytical improvement following treatment with dantrolene. The patient was discharged from hospital with no sequelae a few days after onset of the condition.

Síndrome neuroléptico maligno en paciente postoperada: a propósito de un caso / Neuroleptic malignant syndrome in a postoperative patient: a case report

El síndrome neuroléptico maligno es una emergencia médica poco frecuente asociada al uso de antipsicóticos y otros fármacos antidopaminérgicos. No se dispone de una prueba específica para su diagnóstico, basándose este en una alta sospecha clínica y la realización de un buen diagnóstico diferencial. Un cuadro clínico compatible, destacando la hipertermia, rigidez muscular, alteración del nivel de conciencia y signos de rabdomiolisis en los estudios analíticos, junto con el antecedente de la toma de fármacos neurolépticos, constituyen los elementos clave para la detección de esta entidad. Debido a su escasa incidencia y su potencial mortalidad, es primordial su conocimiento a través de series de casos descritos en la literatura para facilitar su sospecha diagnóstica ante un caso clínico compatible. A continuación, exponemos un caso de una paciente de 79 años con consumo crónico de alcohol como único antecedente de interés, que recibió una dosis única de haloperidol tras un cuadro de delirio en el contexto de un postoperatorio convencional de traumatología. Posteriormente, desarrolló un cuadro de deterioro progresivo del nivel de conciencia, diaforesis, rigidez muscular generalizada, hipertermia, junto a acidosis metabólica severa, hiperlactacidemia, rabdomiolisis, hipertransaminasemia e hipocalcemia. Tras excluir otras entidades compatibles con la clínica, el síndrome neuroléptico maligno se postuló como la principal hipótesis diagnóstica, reforzándose el diagnóstico tras la mejoría clínica y analítica evidente posterior al inicio del tratamiento con dantrolene. La paciente pudo, finalmente, ser dada de alta escasos días después del inicio del cuadro sin presentar secuelas.(AU)

Neuroleptic malignant syndrome is a rare medical emergency associated with the use of antipsychotics and other antidopaminergic drugs. There is no specific test, and diagnosis is based on high clinical suspicion and good differential diagnosis.A clinical picture consistent with hyperthermia, muscle rigidity, altered level of consciousness, together with signs of rhabdomyolysis in analytical studies and a history of taking neuroleptic drugs are the key elements in the detection of this entity.Due to its low incidence and potential mortality, it is essential to publish case reports of neuroleptic malignant syndrome in order to raise awareness of this entity and facilitate diagnostic suspicion when encountering a patient with compatible symptoms.The following is the case of a 79 year old patient with chronic alcohol consumption as the only history of interest, who was given a single dose of haloperidol after an episode of delirium in the postoperative period of conventional trauma surgery. She subsequently developed a picture of progressive deterioration of the level of consciousness, diaphoresis, generalized muscle rigidity, hyperthermia, together with severe metabolic acidosis, hyperlacticaemia, rhabdomyolysis, hypertransaminasemia and hypocalcemia. After ruling out other entities compatible with the clinical picture, neuroleptic malignant syndrome was given as the main diagnostic hypothesis. Diagnosis was confirmed after clinical and analytical improvement following treatment with dantrolene. The patient was discharged from hospital with no sequelae a few days after onset of the condition.(AU)

Una experiencia con la Comunidad Indígena Pijao JISHXManayx (Hola Y Bienvenidos) / An experience with the indigenous pijao community Jishx Manayx hello and welcome

Un deseo intenso de rescate por la cultura y costumbres debería imperar en el siglo XXI. La tecnificación e insensibilidad con la que luchamos debe ser contrarrestada por las sendas antiguas en cuanto al rescate de principios, valores, fundamentos para vivir en armonía con todos los seres vivos del entorno. Una vida sencilla que nos haga ver lo realmente importante, que es mirar a los ojos y reconocer la sabiduría de los ancianos, sentir los olores de la cocina tradicional, prevenir la desarmonía o enfermedad o curarnos con la fe y usar recetas ancestrales, escuchar el consejo y las tradiciones de los abuelos y cocer alrededor del fuego historias inacabadas que deben seguir siendo escritas por nuestros niños y jóvenes [Fragmento de texto] (AU)

Neuroleptic malignant syndrome in a postoperative patient: a case report. / Síndrome neuroléptico maligno en paciente postoperada: a propósito de un caso.

Neuroleptic malignant syndrome is a rare medical emergency associated with the use of antipsychotics and other antidopaminergic drugs. There is no specific test, and diagnosis is based on high clinical suspicion and good differential diagnosis. A clinical picture consistent with hyperthermia, muscle rigidity, altered level of consciousness, together with signs of rhabdomyolysis in analytical studies and a history of taking neuroleptic drugs are the key elements in the detection of this entity. Due to its low incidence and potential mortality, it is essential to publish case reports of neuroleptic malignant syndrome in order to raise awareness of this entity and facilitate diagnostic suspicion when encountering a patient with compatible symptoms. The following is the case of a 79 year old patient with chronic alcohol consumption as the only history of interest, who was given a single dose of haloperidol after an episode of delirium in the postoperative period of conventional trauma surgery. She subsequently developed a picture of progressive deterioration of the level of consciousness, diaphoresis, generalized muscle rigidity, hyperthermia, together with severe metabolic acidosis, hyperlacticaemia, rhabdomyolysis, hypertransaminasemia and hypocalcemia. After ruling out other entities compatible with the clinical picture, neuroleptic malignant syndrome was given as the main diagnostic hypothesis. Diagnosis was confirmed after clinical and analytical improvement following treatment with dantrolene. The patient was discharged from hospital with no sequelae a few days after onset of the condition.

High D dimers and low global fibrinolysis coexist in COVID19 patients: what is going on in there?

BACKGROUD: COVID-19 coagulopathy linked to increased D-dimer levels has been associated with high mortality (Fei Z et al. in Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet (London, England) 395(10229):1054-62, 2020). While D-dimer is accepted as a disseminated intravascular coagulation marker, rotational thromboelastometry (ROTEM) also detects fibrinolysis (Wright FL et al. in Fibrinolysis shutdown correlates to thromboembolic events in severe COVID-19 infection. J Am Coll Surg (2020). Available from https://pubmed.ncbi.nlm.nih.gov/32422349/ [cited 14 Jun 2020]; Schmitt FCF et al. in Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care 9(1):19, 2019). We describe the ROTEM profile in severely ill COVID-19 patients and compare it with the standard laboratory coagulation test. METHODS: Adult patients diagnosed with COVID-19 admitted to the ICU were prospectively enrolled after Ethics Committee approval (HCB/2020/0371). All patients received venous thromboembolism prophylaxis; those on therapeutic anticoagulation were excluded. The standard laboratory coagulation test and ROTEM were performed simultaneously at 24-48 h after ICU admission. Sequential organ failure assessment (SOFA), disseminated intravascular coagulation (DIC) and sepsis-induced coagulopathy (SIC) scores were calculated at sample collection. RESULTS: Nineteen patients were included with median SOFA-score of 4 (2-6), DIC-score of 1 (0-3) and SIC-score of 1.8 (0.9). Median fibrinogen, D-dimer levels and platelet count were 6.2 (4.8-7.6 g/L), 1000 (600-4200 ng/ml) and 236 (136-364 109/L), respectively. Clot firmness was above the normal range in the EXTEM and FIBTEM tests while clot lysis was decreased. There was no significant correlation between ROTEM or D-dimer parameters and the SOFA score. CONCLUSION: In COVID-19 patients, the ROTEM pattern was characterized by a hypercoagulable state with decreased fibrinolytic capacity despite a paradoxical increase in D-dimer levels. We suggest that, in COVID-19 patients, the lungs could be the main source of D-dimer, while a systemic hypofibrinolytic state coexists. This hypothesis should be confirmed by future studies.

Concordancia diagnóstica del sistema de graduación Chisholm Mason y Focus Score en la sialoadenitis linfocítica focal como aproximación al síndrome de Sjögren / Diagnostic agreement of the Chisholm Mason and Focus Score grading system in focal lymphocytic sialadenitis in patients with dry symptoms

RESUMEN Introducción: Existen diferentes sistemas de graduación para interpretar la biopsia de glándula salival menor (BGSM) en pacientes con síntomas secos. En la actualidad la metodología recomendada (Focus Score [FS]), aunque no se emplea de forma rutinaria, conlleva discrepancias diagnósticas. Objetivo: Determinar la concordancia de la lectura histopatológica de BGSM entre las técnicas FS y Chisholm Mason (CM) para el diagnóstico de sialoadenitis linfocítica focal en el hospital de San José, entre enero de 2017 y junio de 2018. Métodos: Estudio de concordancia. Se incluyeron BGSM de pacientes con síntomas secos. Se excluyó material no apto para el estudio, o con menos de 4 lóbulos o menos de 8 mm de área. Se clasificaron utilizando las técnicas FS y CM por 2 evaluadores independientes. Se evaluó el acuerdo interobservador, intraobsevador y global entre las pruebas mediante el coeficiente de Kappa de Cohen. Resultados: Se evaluaron 130 biopsias. Los valores K intraobservador entre FS y CM fueron 0,42 para el observador 1 y 0,23 para el observador 2. Los valores K del acuerdo interobservador fueron 0,47 para FS y 0,65 para CM. La concordancia entre los 2 sistemas de puntuación fue K de 0,13. Conclusiones: Se evidencia una probable sobreestimación de focos con CM, que resalta sus debilidades, y mayor precisión con FS. Por ende, la concordancia entre las 2 pruebas es débil. Es necesario un mayor esfuerzo para el uso del método estandarizado de lectura de BGSM con el FS para una correcta interpretación y beneficio en la clasificación de pacientes con síndrome seco.

ABSTRACT Introduction: There are different grading systems for interpreting the minor salivary gland biopsy (MSGB) in patients with dry symptoms (Sicca). The recommended methodology is currently the Focus Score (FS), which, although not performed routinely, results in diagnostic discrepancies. Objective: To determine the concordance of the histopathological reading of MSGB between the FS and Chisholm Mason (CM) techniques for diagnosis of focal lymphocytic sialadenitis at the San José Hospital between January 2017 and June 2018. Methods: Concordance study. MSGB of patients with sicca symptoms were included. Material not suitable for study and / or with less than 4 lobules and / or less than 8 mm of surface area was excluded. They were classified, using the FS and CM techniques, by two independent evaluators. The inter-observer, intra-observer, and overall agreement between the tests were evaluated using Cohen's Kappa coefficient. Results: A total of 130 biopsies were evaluated. The intra-observer K values between FS and CM were 0.42 for observer 1, and 0.23 for observer 2. The K values of the inter-observer agreement were 0.47 for FS, and 0.65 for CM. The concordance between the two scoring systems was K = 0.13. Conclusions: There is evidence of a probable over-estimation of foci with CM, highlighting its weaknesses and greater precision with FS technique, resulting in the weak concordance between the two tests. A greater effort is necessary for the use of the standardised MSGB FS reading method for a correct interpretation and benefit in the classification of patients with dry syndrome.

Angiogenesis in cardiopulmonary dirofilariosis: does the Wolbachia surface protein have a pro- or anti-angiogenic effect?

Cardiopulmonary dirofilariosis caused by Dirofilaria immitis produces inflammation, blood vessel obstruction and hypoxia, which are required conditions for the beginning of the process of neovascularization. Since D. immitis harbours intracellular symbiotic Wolbachia bacterium, the global understanding of the angiogenic process requires the analysis of the effect of the parasite molecules, but also that of Wolbachia. Canine primary lung microvascular endothelial cells were treated with the recombinant Wolbachia surface protein (rWSP) and the expression of angiogenic factors like Vascular Endothelial Growth Factor-A (VEGF-A), sFlt, membrane Endoglin (mEndoglin) and soluble Endoglin (sEndoglin), as well as the in vitro formation of pseudocapillaries, were measured. The analyses showed a significant increase in the expression of pro-angiogenic VEGF-A and anti-angiogenic sEndoglin, together with a significant decrease in both pro-angiogenic mEndoglin and pseudocapillary formation, compared to untreated controls. Due to the complexity of the angiogenic process and its relationship with other physiological processes like inflammation and fibrinolysis, these results might suggest that rWSP participate in various mechanisms related to each other and its effects might depend either on the balance between them or on the moment of their occurrence.

Síntomas visuales y oculares sin causa: La necesidad de un enfoque psicosomático en oftalmología / Unexplained ocular and visual symptoms: The need for a psychosomatic approach in Ophthalmology

INTRODUCCIÓN: Es reconocida la asociación de algunos síntomas somáticos sin causa orgánica con conflictos psíquicos. En oftalmología existen pocos estudios que evalúen esta asociación, y en los actuales Programas de Formación de Residentes en Oftalmología no se incluye entrenamiento formal en Psicosomática. Esto determina que los fenómenos psicosomáticos en la clínica oftalmológica no sean reconocidos, reduciendo la eficacia terapéutica, la satisfacción de pacientes y médicos, e incrementando los costos en salud. El objetivo de este estudio fue caracterizar a pacientes con síntomas visuales/oculares idiopáticos (SVI) y estimar la prevalencia de indicadores de conflictos psíquicos (CP) en ellos. Materiales y métodos: Se reclutaron pacientes con SVI durante 12 meses en una consulta oftalmológica. Descartando causa orgánica, se pesquisó en la historia clínica indicadores de CP: diagnóstico psiquiátrico, uso de psicofármacos, enfermedades psicosomáticas en otros órganos y presencia de crisis biográficas recientes. Se comparó resultados con grupo control. RESULTADOS: Se registraron 39 pacientes con SVI, con una incidencia aproximada del 3%, siendo el 74% mujeres, y su edad promedio 41,8 años. Los SVI más frecuentes fueron: irritación de la superficie ocular (51%) y trastornos visuales inespecíficos (17%). Todos los pacientes presentaron al menos un criterio de CP, incluyendo 46,2% psicodiagnóstico, 48,7% usuarios psicofármacos, 48,7% crisis biográficas recientes y 64% enfermedades psicosomáticas en otros órganos. La frecuencia de psicodiagnóstico y enfermedades psicosomáticas en otros órganos fue estadísticamente superior (p < 0,05) con relación al grupo control. CONCLUSIONES: Pacientes con SVI presentan una alta frecuencia de indicadores de CP. Aunque no es posible asumir un rol causal de los CP en los SVI, su presencia debe alertar al oftalmólogo de la necesidad de la apropiada evaluación e intervención psicológica

INTRODUCTION: Psychogenic causes for some somatic symptoms have been widely recognised. In Ophthalmology however, there are few studies that address this issue, and current Ophthalmology Training Programs do not include formal teaching in Psychosomatics. Psychosomatic phenomena in ophthalmology are probably under-diagnosed, which may reduce therapeutic effectiveness, decrease patient and physician satisfaction, and increase health costs due to multiple consultations and prescriptions. The aims of this study were to describe patients with unexplained visual/ocular symptoms (UVOS), and to estimate the prevalence of psychological distress (PD) among them. MATERIALS AND METHODS: Consecutive adults with UVOS were recruited over a 12 month period. Complete medical history and ocular examination were performed to rule out organic disease. Psychological Distress was defined by the presence of one or more of the following criteria: psychiatric diagnosis, use of psychotropic medication, psychosomatic disease in other organs, and biographical crisis in the last 6 months. Results were compared with a control group. RESULTS: A total of 39 cases of UVOS were recruited, corresponding approximately to 3% prevalence. The large majority (74%) were female. The mean age was 41.8 years. The most common complaints were ocular surface irritation symptoms (51%) and unspecific visual disturbances (17%). At least 1 of the PD criteria was found in 100%, including 46.2% with psychiatric comorbidity, 48.7% with psychotropic medications, 64% with psychosomatic disease in other organs, and 48.7% with recent life-stressful events. PD indicators were statistically higher compared with control group (P < .05). CONCLUSIONES: There was a high frequency of PD indicators in patients with UVOS. Although the causative role of PD remains unclear, the presence of UVOS should warn the ophthalmologist of an underlying psychic conflict and to make an appropriate psychological intervention

Unexplained ocular and visual symptoms: The need for a psychosomatic approach in Ophthalmology. / Síntomas visuales y oculares sin causa: La necesidad de un enfoque psicosomático en oftalmología.

INTRODUCTION: Psychogenic causes for some somatic symptoms have been widely recognised. In Ophthalmology however, there are few studies that address this issue, and current Ophthalmology Training Programs do not include formal teaching in Psychosomatics. Psychosomatic phenomena in ophthalmology are probably under-diagnosed, which may reduce therapeutic effectiveness, decrease patient and physician satisfaction, and increase health costs due to multiple consultations and prescriptions. The aims of this study were to describe patients with unexplained visual/ocular symptoms (UVOS), and to estimate the prevalence of psychological distress (PD) among them. MATERIALS AND METHODS: Consecutive adults with UVOS were recruited over a 12 month period. Complete medical history and ocular examination were performed to rule out organic disease. Psychological Distress was defined by the presence of one or more of the following criteria: psychiatric diagnosis, use of psychotropic medication, psychosomatic disease in other organs, and biographical crisis in the last 6 months. Results were compared with a control group. RESULTS: A total of 39 cases of UVOS were recruited, corresponding approximately to 3% prevalence. The large majority (74%) were female. The mean age was 41.8 years. The most common complaints were ocular surface irritation symptoms (51%) and unspecific visual disturbances (17%). At least 1 of the PD criteria was found in 100%, including 46.2% with psychiatric comorbidity, 48.7% with psychotropic medications, 64% with psychosomatic disease in other organs, and 48.7% with recent life-stressful events. PD indicators were statistically higher compared with control group (P<.05). CONCLUSIONES: There was a high frequency of PD indicators in patients with UVOS. Although the causative role of PD remains unclear, the presence of UVOS should warn the ophthalmologist of an underlying psychic conflict and to make an appropriate psychological intervention.

Development of a tool for screening adverse food reactions and food allergy in Portuguese children

Introduction and objectives: A standardised questionnaire may be an excellent tool for epidemiological studies aiming at screening children with suspected food allergies. Thus, the aim of the present study was to develop a screening questionnaire for assessing children with suspected food allergy and to analyse its reproducibility. Materials and methods: A questionnaire of adverse food reactions was developed by literary review of similar questionnaires validated in other countries as well as less well defined, non-validated Portuguese questionnaires. Peer review of the questionnaire by a panel of specialists and subsequent exploratory analysis was carried out by applying the questionnaire in children with confirmed food allergy. Test-retest analysis was performed by giving a face-to-face questionnaire to 159 children with suspected adverse food reactions, aged between three and 11 years. Temporal stability using Spearman Rho correlation test and reproducibility was studied using Cohen's Kappa index. Results: 115 children confirmed adverse food reactions that occurred with one or more foods. Retest was given about three weeks after the test, to 50 of these children who were randomly selected. The questionnaire showed good temporal stability (Spearman correlation coefficient of 0.834), and good reproducibility (only two of the 27 items had a Kappa index < 0.60). Conclusions. This questionnaire showed good temporal stability and reproducibility. Its validation for screening children with suspected food allergy will allow a standardised approach to diagnosis and comparison of results obtained in different centres

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Effects of maternal protein restriction during pregnancy and lactation on milk composition and offspring development.

Before weaning, breast milk is the physiological form of neonatal nutrition, providing pups with all nutrient requirements. Maternal low-protein diet (LPD) during pregnancy and lactation induces adverse changes in key maternal organs, which have negative effects on pup development. We studied the effects of maternal LPD on liver weight, mammary gland (MG) cell differentiation, milk composition and production and pup development throughout lactation. We fed rats with control (C) or LPD (R) during pregnancy and lactation. At 7 d early, 14 d mid and 21 d late lactation stages, maternal biochemical parameters, body, liver and MG weights were analysed. MG cell differentiation was analysed by haematoxylin and eosin staining; milk nutrient composition and production were studied; pup body, liver and brain weights, hippocampal arachidonic acid (AA) and DHA were quantified. Results showed lower body and liver weights, minor MG cell differentiation and lower serum insulin and TAG in R compared with C. R milk contained less protein and higher AA at early and mid stages compared with C. R pup milk and fat intake were lower at all stages. R protein intake at early and mid stages and DHA intake at mid and late stages were lower compared with C. In R pups, lower body, liver and brain weights were associated with decreased hippocampal AA and DHA. We conclude that maternal LPD impairs liver and MG function and induces significant changes in maternal milk composition, pup milk intake and organ development.

Development of a tool for screening adverse food reactions and food allergy in Portuguese children.

INTRODUCTION AND OBJECTIVES: A standardised questionnaire may be an excellent tool for epidemiological studies aiming at screening children with suspected food allergies. Thus, the aim of the present study was to develop a screening questionnaire for assessing children with suspected food allergy and to analyse its reproducibility. MATERIALS AND METHODS: A questionnaire of adverse food reactions was developed by literary review of similar questionnaires validated in other countries as well as less well defined, non-validated Portuguese questionnaires. Peer review of the questionnaire by a panel of specialists and subsequent exploratory analysis was carried out by applying the questionnaire in children with confirmed food allergy. Test-retest analysis was performed by giving a face-to-face questionnaire to 159 children with suspected adverse food reactions, aged between three and 11 years. Temporal stability using Spearman Rho correlation test and reproducibility was studied using Cohen's Kappa index. RESULTS: 115 children confirmed adverse food reactions that occurred with one or more foods. Retest was given about three weeks after the test, to 50 of these children who were randomly selected. The questionnaire showed good temporal stability (Spearman correlation coefficient of 0.834), and good reproducibility (only two of the 27 items had a Kappa index <0.60). CONCLUSIONS: This questionnaire showed good temporal stability and reproducibility. Its validation for screening children with suspected food allergy will allow a standardised approach to diagnosis and comparison of results obtained in different centres.

Protección de la salud mental en la emergencia social: reflexiones y orientaciones para profesionales de la salud mental / Mental health protection in the social emergency: reflections and guidelines for mental health workers

Las situaciones de emergencias y desastres causan sufrimiento y aumentan los problemas de salud mental de las poblaciones afectadas. Existen publicaciones nacionales e internacionales que entregan estrategias y orientaciones para proteger la salud mental de la población en estas situaciones. El estallido social ocurrido en Chile en octubre de 2019 presenta algunas particularidades que hacen necesario revisar conceptos y utilizarlos de manera pragmática para que los profesionales de salud podamos colaborar no sólo en la disminución del malestar y secuelas de eventos que han movilizado afectivamente a todo un país, sino que también como herramientas para lidiar con la ansiedad propia. En el artículo se propone el término de Emergencia Social para definir de manera más precisa el fenómeno. Se plantea la importancia de identificar y combatir la Ansiedad Persecutoria como mecanismo que promueve la polarización violenta a nivel individual y colectivo. Por último, se mencionan algunas recomendaciones generales respecto a las estrategias para proteger la salud mental de la población y recomendaciones específicas respecto del rol de los profesionales de salud mental en situaciones de emergencia.

Simvastatin interferes with cancer 'stem-cell' plasticity reducing metastasis in ovarian cancer.

Cell plasticity of 'stem-like' cancer-initiating cells (CICs) is a hallmark of cancer, allowing metastasis and cancer progression. Here, we studied whether simvastatin, a lipophilic statin, could impair the metastatic potential of CICs in high-grade serous ovarian cancer (HGS-ovC), the most lethal among the gynecologic malignancies. qPCR, immunoblotting and immunohistochemistry were used to assess simvastatin effects on proteins involved in stemness and epithelial-mesenchymal cell plasticity (EMT). Its effects on tumor growth and metastasis were evaluated using different models (e.g., spheroid formation and migration assays, matrigel invasion assays, 3D-mesomimetic models and cancer xenografts). We explored also the clinical benefit of statins by comparing survival outcomes among statin users vs non-users. Herein, we demonstrated that simvastatin modifies the stemness and EMT marker expression patterns (both in mRNA and protein levels) and severely impairs the spheroid assembly of CICs. Consequently, CICs become less metastatic in 3D-mesomimetic models and show fewer ascites/tumor burden in HGS-ovC xenografts. The principal mechanism behind statin-mediated effects involves the inactivation of the Hippo/YAP/RhoA pathway in a mevalonate synthesis-dependent manner. From a clinical perspective, statin users seem to experience better survival and quality of life when compared with non-users. Considering the high cost and the low response rates obtained with many of the current therapies, the use of orally or intraperitoneally administered simvastatin offers a cost/effective and safe alternative to treat and potentially prevent recurrent HGS-ovCs.

La secuenciación masiva (NGS) como método diagnóstico en la enfermedad de Stargardt / Next generation sequencing in the diagnosis of Stargardt's disease

Introducción: La enfermedad de Stargardt es la maculopatía más frecuente en la edad infantil y adulta. Presenta un origen genético por afectación principalmente del gen ABCA4 con herencia autosómica recesiva. Se trata de un gen con características especiales por su gran tamaño y comportamiento, mostrando una elevada tasa de mutaciones. La aparición, desarrollo y accesibilidad económica de las técnicas de secuenciación masiva permiten realizar el diagnóstico genético de la enfermedad de Stargardt. Pacientes y métodos: Se presentan 2 casos clínicos diagnosticados genéticamente de enfermedad de Stargardt mediante la realización de un panel de secuenciación masiva de 298 genes. Resultados: Los pacientes presentaban un fenotipo de maculopatía de ojo de buey con ausencia de flecks y las siguientes mutaciones: c.G5882A:p.Gly1961Glu y c.C3056T:p.T1019M para el caso 1; c.G5882A:p.Gly1961Glu y c.287del:p.Asn96Thrfs·19 para el caso 2. Ambos pacientes comparten la mutación c.G588A:2p.Gly1961Glu que explica su fenotipo similar característico. Conclusiones: La secuenciación masiva es especialmente útil en la enfermedad de Stargardt, pues el gen ABCA4 presenta un gran tamaño y elevada heterogeneidad polimórfica, que se traduce en una amplia variabilidad clínica (AU)

Introduction: Stargardt's disease is the most frequent form of inherited macular dystrophy in children and adults. It is a genetic eye disorder caused by mutations in ABCA4 gene with an autosomal recessive inheritance. ABCA4 is a very polymorphic and large gene containing 50 exons. The development of next generation sequencing (NGS) can be used for the genetic diagnosis of this disease. Patients and methods: A report is presented on two patients with a clinical diagnosis of Stargardt's disease whose genetic confirmation was performed by a NGS panel of 298 genes. Results: Clinically, the patients showed bull's eye maculopathy and absence of flecks, and genetically they shared the Gly1961Glu mutation that could explain their common phenotype, together with c.C3056T:p.T1019M for case 1, and c.287del:p.Asn96Thrfs·19 for case 2. Conclusions: NGS is particularly useful in the diagnosis of Stargardt's disease as ABCA4 is a large gene with a high allelic heterogeneity that causes a wide range of clinical manifestations (AU)