[Mills' syndrome]. / Sindrom Millsa.

Mills' syndrome is an idiopathic, slowly progressive ascending spastic hemiparesis. Some authors consider it as a unilateral variant of progressive lateral sclerosis. Due to the rarity of the disease and the slow clinical course, this article presents a clinical case and discusses the diagnostic criteria for the syndrome.

Revisión Sistemática - Intervenciones en el proceso de Retorno al Trabajo en los Trastornos Mentales Comunes / Systematic review - Interventions process to return to Work in Common Mental Disorders

Introducción: Los trastornos mentales comunes (TMC), causan sufrimiento individual y menoscabo significativo a la salud, tienen un impacto negativo en el bienestar del individuo, las circunstancias financieras y a la sociedad. La respuesta de los médicos ha sido otorgar la incapacidad con la finalidad de mitigar los síntomas. Pero el dilema que entraña esta respuesta es que el reposo es beneficioso sólo si mantiene un equilibrio funcional del paciente y el retorno al trabajo. Bajo este enfoque, se plantea que las intervenciones psicosociales permiten preparar al individuo para retornar al trabajo. Método: el diseño de esta revisión es de alcance descriptivo y de enfoque mixto. La búsqueda se realizó a partir de: PubMed/MEDLINE, ELSEVIER, SciELO, Academic Google. El criterio de temporalidad fueron artículos publicados en los últimos 5 años, desde el 06 de diciembre y finalizo el 30 de diciembre del 2019. Resultados: se analizaron 28 artículos a texto completo, la evidencia científica se sustentó en 13 estudios controlados. Se encontró evidencia de calidad moderada de que las intervenciones aplicadas mejoran los síntomas y reducen el número de días de incapacidad en pacientes con TMC. Nivel de evidencia B de GRADE. Conclusiones: las intervenciones psicosociales facilitan un retorno al trabajo saludable y sostenible. Sin embargo, para que esto suceda, estas deben dirigirse no solo al individuo con incapacidad para trabajar, sino también a la interacción de este con su lugar de trabajo. (AU)

Introduction: Common mental disorders (CMD), cause individual suffering and significate impairment to health, have a negative impact on the well-being of the individual, financial circumstances and society. Physicians’ response has been to grant disability in order to mitigate symptoms. But the dilemma involved in this response is that rest is beneficial only if it maintains a functional balance for the patient and return to work. Under this approach, it is stated that psychosocial interventions allow preparing the individual to return to work. Method: The design of this review is descriptive in scope and mixed in approach. The search was carried out from the following databases: PubMed/MEDLINE, ELSEVIER, SciELO, Academic Google. Temporality search criteria were articles published in the last 5 years, from December 06 to December 30, 2019. Results: 28 full-text articles were analyzed; the scientific evidence was supported in 13 controlled studies. We found a moderate evidence that the interventions applied improve symptoms and reduce the number of days of disability in patients with CMD. Evidence level B of GRADE. Conclusions: psycho-social interventions facilitate a healthy and sustainable return to work. However, for this to happen, they must address not only the individual with an inability to work, but also their interaction with their workplace. (AU)

Síndrome miasteniforme de Lambert-Eaton / Lambert-Eaton myasthenic syndrome

Introducción: El síndrome miasteniforme de Lambert-Eaton (LEMS) es una patología paraneoplásica (T-LEMS) o idiopática autoinmunitaria (NT-LEMS) ocasionada por autoanticuerpos contra los canales de calcio dependientes del voltaje presinápticos de la unión neuromuscular. El 60% de los T-LEMS se asocia a carcinoma de pulmón de células pequeñas. Una puntuación Dutch-English LEMS Tumor Association Prediction (DELTA-P) mayor de 3 denota un riesgo elevado de dicha asociación. El diagnóstico precoz fundado en los hallazgos clínicos, estudios neurofisiológicos y dosificación de títulos de anticuerpos en el suero permite iniciar tempranamente el tratamiento sintomático y la búsqueda oncológica. Son escasos los informes de pacientes con LEMS en Latinoamérica. Objetivo: Describir las características de pacientes con LEMS de un centro privado de Buenos Aires, Argentina, y compararlas con las de otras series publicadas. Pacientes y métodos: Se revisaron historias clínicas de 13 pacientes con LEMS con hallazgos clínicos, electromiograma compatible y/o anticuerpos positivos. Se realizó seguimiento hasta descartar o confirmar una neoplasia asociada de acuerdo con los algoritmos recomendados. Resultados: Cuatro pacientes presentaron diagnóstico de T-LEMS, dos de ellos con carcinoma de pulmón de células pequeñas. De los nueve pacientes con NT-LEMS, cinco presentaron una puntuación DELTA-P de 3 y 4. Nueve pacientes presentaron la tríada clínica clásica desde el inicio. Todos los pacientes presentaron en el electromiograma hallazgos compatibles con defecto de placa neuromuscular presináptico. El 70% mejoró sintomáticamente con piridostigmina. Conclusiones: Los hallazgos clínicos, junto con los estudios neurofisiológicos compatibles, resultan suficientes para el diagnóstico de LEMS. No pudo replicarse la relación entre puntuación DELTA-P y riesgo de carcinoma de pulmón de células pequeñas...(AU)

Introduction: Early diagnosis based on clinical findings, neurophysiological studies and serum antibody titres allows early initiation of symptomatic treatment and oncological screening. Reports of patients with LEMS in Latin America are scarce. Aim: This article aims to describe the characteristics of patients with LEMS from a private centre in Buenos Aires, Argentina, and to compare them with those of other series that have been published. Patients and methods: The medical records of 13 patients with LEMS with clinical findings, compatible electromyogram and/or positive antibodies were reviewed. Follow-up was performed until associated neoplasia was ruled out or confirmed according to the recommended algorithms. Results: Four patients were diagnosed with T-LEMS, two of them with small-cell lung carcinoma. Of the nine patients with NT-LEMS, five had a DELTA-P score of 3 and 4. Nine patients presented with the classic clinical triad from the onset of the disease. All patients had electromyogram findings compatible with presynaptic neuromuscular plaque defect. Of the total, 70% improved symptomatically with pyridostigmine. Conclusions: The clinical findings, together with compatible neurophysiological studies, are sufficient for the diagnosis of LEMS. The relationship between the DELTA-P score and the risk of small-cell lung carcinoma could not be replicated. Symptomatic treatment with pyridostigmine represents an effective therapeutic alternative.(AU)

[Lambert-Eaton myasthenic syndrome]. / Síndrome miasteniforme de Lambert-Eaton.

INTRODUCTION: Early diagnosis based on clinical findings, neurophysiological studies and serum antibody titres allows early initiation of symptomatic treatment and oncological screening. Reports of patients with LEMS in Latin America are scarce. AIM: This article aims to describe the characteristics of patients with LEMS from a private centre in Buenos Aires, Argentina, and to compare them with those of other series that have been published. PATIENTS AND METHODS: The medical records of 13 patients with LEMS with clinical findings, compatible electromyogram and/or positive antibodies were reviewed. Follow-up was performed until associated neoplasia was ruled out or confirmed according to the recommended algorithms. RESULTS: Four patients were diagnosed with T-LEMS, two of them with small-cell lung carcinoma. Of the nine patients with NT-LEMS, five had a DELTA-P score of 3 and 4. Nine patients presented with the classic clinical triad from the onset of the disease. All patients had electromyogram findings compatible with presynaptic neuromuscular plaque defect. Of the total, 70% improved symptomatically with pyridostigmine. CONCLUSIONS: The clinical findings, together with compatible neurophysiological studies, are sufficient for the diagnosis of LEMS. The relationship between the DELTA-P score and the risk of small-cell lung carcinoma could not be replicated. Symptomatic treatment with pyridostigmine represents an effective therapeutic alternative.

TITLE: Síndrome miasteniforme de Lambert-Eaton.Introducción. El síndrome miasteniforme de Lambert-Eaton (LEMS) es una patología paraneoplásica (T-LEMS) o idiopática autoinmunitaria (NT-LEMS) ocasionada por autoanticuerpos contra los canales de calcio dependientes del voltaje presinápticos de la unión neuromuscular. El 60% de los T-LEMS se asocia a carcinoma de pulmón de células pequeñas. Una puntuación Dutch-English LEMS Tumor Association Prediction (DELTA-P) mayor de 3 denota un riesgo elevado de dicha asociación. El diagnóstico precoz fundado en los hallazgos clínicos, estudios neurofisiológicos y dosificación de títulos de anticuerpos en el suero permite iniciar tempranamente el tratamiento sintomático y la búsqueda oncológica. Son escasos los informes de pacientes con LEMS en Latinoamérica. Objetivo. Describir las características de pacientes con LEMS de un centro privado de Buenos Aires, Argentina, y compararlas con las de otras series publicadas. Pacientes y métodos. Se revisaron historias clínicas de 13 pacientes con LEMS con hallazgos clínicos, electromiograma compatible y/o anticuerpos positivos. Se realizó seguimiento hasta descartar o confirmar una neoplasia asociada de acuerdo con los algoritmos recomendados. Resultados. Cuatro pacientes presentaron diagnóstico de T-LEMS, dos de ellos con carcinoma de pulmón de células pequeñas. De los nueve pacientes con NT-LEMS, cinco presentaron una puntuación DELTA-P de 3 y 4. Nueve pacientes presentaron la tríada clínica clásica desde el inicio. Todos los pacientes presentaron en el electromiograma hallazgos compatibles con defecto de placa neuromuscular presináptico. El 70% mejoró sintomáticamente con piridostigmina. Conclusiones. Los hallazgos clínicos, junto con los estudios neurofisiológicos compatibles, resultan suficientes para el diagnóstico de LEMS. No pudo replicarse la relación entre puntuación DELTA-P y riesgo de carcinoma de pulmón de células pequeñas. El tratamiento sintomático con piridostigmina representa una alternativa terapéutica eficaz.

Vasculitic Peripheral Neuropathy, Differences Between Systemic and Non-Systemic Etiologies: A Case Series and Biopsy Report.

BACKGROUND: Vasculitic peripheral neuropathy (VPN) is caused by vessel inflammation leading to peripheral nerve injury of acute-to-subacute onset. When VPN occurs in the context of systemic disease it is classified as Systemic Vasculitic Neuropathy (SVN) and as Non-Systemic Vasculitic Neuropathy (NSVN) when restricted to the nerves. OBJECTIVE: This study aimed to compare the clinical characteristics, biopsy findings and disease outcome in patients with VPN. METHODS: Clinical records of adult patients with VPN diagnosed at our institution between June-2002 and June-2019 were retrospectively reviewed. Demographic characteristics, clinical manifestations, nerve conduction studies, nerve biopsies, treatment and clinical evolution were analyzed in all patients with at least 6 months follow-up. RESULTS: Twenty-five patients with VPN were included (SVN, n = 10; NSVN, n = 15). No significant differences in demographic or clinical features were found between groups. The median delay between symptom onset and nerve biopsy was significantly longer in NSVN patients (10 vs 5.5 months, p = 0.009). Erythrocyte sedimentation rate (ESR) values over 20 mm/h were significantly more common in SVN patients (100% vs. 60%, p = 0.024). Nerve biopsies showed active lesions more frequently in treatment-naive patients compared to those who had received at least 2 weeks of corticosteroids (92% vs 38%; p = 0.03), with a higher proportion of definite VPN cases (92 vs 46%; p = 0.04). CONCLUSIONS: Although the clinical manifestations are similar, ESR is an important tool to help distinguish between both conditions. Early nerve biopsy in untreated patients increases diagnostic accuracy, avoiding misdiagnosis.

Ultrafine particles in scanning sprays: a standardized examination of five powders used for dental reconstruction.

BACKGROUND: Intraoral matting sprays for chairside systems can release fine or ultrafine particles or nanoparticles at dentists' workplaces and cause work-related health problems by inhalation exposure. Until now, little is known about the magnitude of the ultrafine fraction, when using these scanning sprays. Hence, more information is needed for workplace risk assessments in dental practices. METHODS: Five commonly used dental spray-powders were examined under standardized conditions. Ingredients were taken from the respective safety data sheet. Particle number-size distributions and total number concentrations were analyzed with a fast mobility particle sizer, and reported graphically as well as mean particle fractions smaller than 100 nm. Based on these measurements, risk assessments were conducted, and particle depositions in the lung were modelled. RESULTS: The mean fraction of particles smaller than 100 nm varied between 9 and 93% depending on the matting agent and mode of application of the intraoral scanning spray. Propellants can represent a large fraction of these particles. Titanium dioxide, pigment-suspensions, talcum and others particles, which can pose relevant health risks, were listed as ingredients of scanning sprays in safety data sheets. Nevertheless, the deposited fraction of hazardous particles in the lung of employees in dental practices seems to be small (15%) during this dental procedure. CONCLUSIONS: Our results suggest that dentists' personnel can be exposed to hazardous fine and ultrafine particles. Though extensive standardized measurements and systematic evaluation of safety data sheets were used for this study, they cannot sufficiently assess and categorize potential workplace-related health risks.

Treatment, outcomes and costs of asthma exacerbations in Chilean children: a prospective multicenter observational study

Objective: To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures. Methods: Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion. Days with oxygen supply and pharmacological treatments received were recorded from the clinical chart. A basic asthma hospitalization basket was defined in order to estimate the average hospitalization cost for a single patient. Six months after discharge, new visits to the Emergency Room (ER), use of systemic corticosteroids and adherence to the controller treatment were evaluated. Results: 396 patients were enrolled. Patients from the public health system and from the north zone received significantly more days of oxygen, systemic corticosteroids and antibiotics. Great heterogeneity in antibiotic use among the participating hospitals was found, from 0 to 92.3% (ICC 0.34, 95% CI 0.16-0.52). The use of aminophylline, magnesium sulfate and ketamine varied from 0 to 36.4% between the different Pediatric Intensive Care Units (ICC 0.353, 95% CI 0.010-0.608). The average cost per inpatient was of $1910 USD. 290 patients (73.2%) completed the follow-up six months after discharge. 76 patients (26.2%) were not receiving any controller treatment and nearly a fourth had new ER visits and use of systemic corticosteroids due to new asthma exacerbations. Conclusions: Considerable practice variation in asthma exacerbations treatment was found among the participating hospitals, highlighting the poor outcome of many patients after hospital discharge, with an important health cost

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Treatment, outcomes and costs of asthma exacerbations in Chilean children: a prospective multicenter observational study.

OBJECTIVE: To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures. METHODS: Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion. Days with oxygen supply and pharmacological treatments received were recorded from the clinical chart. A basic asthma hospitalization basket was defined in order to estimate the average hospitalization cost for a single patient. Six months after discharge, new visits to the Emergency Room (ER), use of systemic corticosteroids and adherence to the controller treatment were evaluated. RESULTS: 396 patients were enrolled. Patients from the public health system and from the north zone received significantly more days of oxygen, systemic corticosteroids and antibiotics. Great heterogeneity in antibiotic use among the participating hospitals was found, from 0 to 92.3% (ICC 0.34, 95% CI 0.16-0.52). The use of aminophylline, magnesium sulfate and ketamine varied from 0 to 36.4% between the different Pediatric Intensive Care Units (ICC 0.353, 95% CI 0.010-0.608). The average cost per inpatient was of $1910 USD. 290 patients (73.2%) completed the follow-up six months after discharge. 76 patients (26.2%) were not receiving any controller treatment and nearly a fourth had new ER visits and use of systemic corticosteroids due to new asthma exacerbations. CONCLUSIONS: Considerable practice variation in asthma exacerbations treatment was found among the participating hospitals, highlighting the poor outcome of many patients after hospital discharge, with an important health cost.

Practice variation among Dutch paediatricians in palivizumab prescription rates: the importance of parental counselling approach.

AIM: To investigate differences in palivizumab prescription rates between Dutch paediatricians, and the role of parent counselling in this practice variation. METHODS: A retrospective chart review of premature infants <32 weeks of gestation, aged less than six months at the start of the winter season, born between January 2012 and July 2014, in three secondary hospital-based paediatric practices in the Netherlands. RESULTS: We included 208 patients, 133 (64%) of whom received palivizumab. Prescription rates varied considerably between the three hospitals: 8% (6/64), 89% (32/36) and 99% (97/98). A noticeable difference in the way parents were counselled about palivizumab was the use of the number needed to treat (NNT). In the hospital with the lowest prescription rate (8%), an NNT of 20 to prevent one hospitalisation was explicitly discussed with parents. Bronchiolitis-related hospital admissions occurred in 11.3% of patients receiving palivizumab compared to 20.0% in nonimmunised infants (p = 0.086). CONCLUSION: Considerable practice variation exists among Dutch paediatricians regarding palivizumab prescription rates. The counselling method seems to play an important role. Presenting palivizumab prophylaxis as a preference-sensitive decision, combined with the explicit use and explanation of an NNT, leads many parents to refrain from respiratory syncytial virus immunisation.

Hospitalizations for asthma exacerbation in Chilean children: A multicenter observational study

BACKGROUND: Asthma hospitalization rates in Chilean children have increased in the last 14 years, but little is known about the factors associated with this. OBJECTIVE: Describe clinical characteristics of children hospitalized for asthma exacerbation. METHODS: Observational prospective cohort study in 14 hospitals. Over a one-year period, children five years of age or older hospitalized with asthma exacerbation were eligible for inclusion. Parents completed an online questionnaire with questions on demographic information, about asthma, indoor environmental contaminant exposure, comorbidities and beliefs about disease and treatment. Disease control was assessed by the Asthma Control Test. Inhalation technique was observed using a checklist. RESULTS: 396 patients were enrolled. 168 children did not have an established diagnosis of asthma. Only 188 used at least one controller treatment at the time of hospitalization. 208 parents said they believed their child had asthma only when they had an exacerbation and 97 correctly identified inhaled corticosteroids as anti-inflammatory treatment. 342 patients used the wrong spacer and 73 correctly performed all steps of the checklist. CONCLUSIONS: Almost half of the patients were not diagnosed with asthma at the time of hospitalization despite having a medical history suggestive of the disease. In the remaining patients with an established diagnosis of asthma potentially modifiable factors like bad adherence to treatment and poor inhalation technique were found. Implementing a nationwide asthma program including continued medical education for the correct diagnosis and follow up of these patients and asthma education for patients and caregivers is needed to reduce asthma hospitalization rates in Chilean children

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Human nasal mucosal C-reactive protein responses after inhalation of ultrafine welding fume particles: positive correlation to systemic C-reactive protein responses.

Exposures to occupationally relevant ultrafine, zinc- and copper-containing welding fumes cause inflammatory responses involving systemic IL-6, C-reactive protein (CRP) and serum amyloid A (SAA), all associated with elevated risk of cardiovascular events. We investigated whether the systemic response is preceded by nasal inflammatory reactions. Fifteen nonsmoking male subjects were exposed for 6 h under controlled conditions to zinc-/copper-containing welding fumes (at 2.5 mg/m3) or ambient air control in a randomized order. Nasal secretions were collected before and at 1, 3, 6, 10, and 29 h after exposure. Nasal levels of selected biomarkers were determined by electrochemiluminescent assays and related to their systemic levels. Nasal interferon-γ (IFN-γ) peaked significantly 1 h after start of exposure compared to baseline. Nasal CRP as well as SAA increased significantly at 10 and 29 h compared to baseline. Receiver operating characteristic (ROC) curve analysis for differentiating welding fume from control exposure was performed: The highest area under ROC curve (AUC) values were found for the CRP increases (10, 29 h versus 0 h): AUC = 0.83, and for IFN-γ increases (1 h versus 0 h): AUC = 0.92. Nasal and systemic changes of CRP at 29 h revealed a strong correlation (Spearman rank test: increases compared to baseline: r = 0.815, p = 0.0022; absolute levels: r = 0.9, p = 0.0002). In conclusion, short-term exposure to a zinc- and copper-containing welding fume causes significant increases of inflammatory mediators in nasal mucosal lining fluid. Therefore, measurement of nasal inflammatory mediators may provide a useful means for occupational surveillance of workers exposed to ultrafine metal fume particles.

Healthcare reimbursement costs of children with type 1 diabetes in the Netherlands, a observational nationwide study (Young Dudes-4).

BACKGROUND: Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children. Studies on costs related to T1DM are scarce and focused primarily on the costs directly related to diabetes. We aimed to investigate both the overall healthcare costs and the more specific costs related to the management of diabetes. METHODS: This is a retrospective and observational, nationwide cohort study of all Dutch children (aged 0-18 years) with T1DM. Data were collected from the national registry for healthcare reimbursement, in which all Dutch insurance companies combine their reimbursement data. In the Netherlands for all Dutch citizens health care is covered by law and all children are treated by hospital-based paediatricians. RESULTS: We analysed 6710 children distributed over 81 hospitals: 475 children in 6 university hospitals and 6235 children in 75 general hospitals. Total reimbursement for all children with T1DM over the period 2009 to 2011 was € 167,494,732 corresponding to an annual mean of € 55,831,577 of total costs and € 8326 euros per child. When comparing small (between 26 and 54 patients), medium (57-84 patients) and large (88-248 patients) general hospitals, costs per patient were highest in the hospitals with the highest number of T1DM patients. The costs for devices, secondary care and pharmaceutics had most impact on total expenditures. Over the study period, there was a slight decrease in per person costs. CONCLUSION: The overall health expenditure of a child with T1DM is more than € 8000 per patient per annum. Given the move towards more device-intensive multidisciplinary care for these patients, the costs of treating T1DM in children are likely to increase further in the coming years.

Hospitalizations for asthma exacerbation in Chilean children: A multicenter observational study.

BACKGROUND: Asthma hospitalization rates in Chilean children have increased in the last 14 years, but little is known about the factors associated with this. OBJECTIVE: Describe clinical characteristics of children hospitalized for asthma exacerbation. METHODS: Observational prospective cohort study in 14 hospitals. Over a one-year period, children five years of age or older hospitalized with asthma exacerbation were eligible for inclusion. Parents completed an online questionnaire with questions on demographic information, about asthma, indoor environmental contaminant exposure, comorbidities and beliefs about disease and treatment. Disease control was assessed by the Asthma Control Test. Inhalation technique was observed using a checklist. RESULTS: 396 patients were enrolled. 168 children did not have an established diagnosis of asthma. Only 188 used at least one controller treatment at the time of hospitalization. 208 parents said they believed their child had asthma only when they had an exacerbation and 97 correctly identified inhaled corticosteroids as anti-inflammatory treatment. 342 patients used the wrong spacer and 73 correctly performed all steps of the checklist. CONCLUSIONS: Almost half of the patients were not diagnosed with asthma at the time of hospitalization despite having a medical history suggestive of the disease. In the remaining patients with an established diagnosis of asthma potentially modifiable factors like bad adherence to treatment and poor inhalation technique were found. Implementing a nationwide asthma program including continued medical education for the correct diagnosis and follow up of these patients and asthma education for patients and caregivers is needed to reduce asthma hospitalization rates in Chilean children.

Systemic serum amyloid A as a biomarker for exposure to zinc and/or copper-containing metal fumes.

Zinc- and copper-containing welding fumes increase systemic C-reactive protein (CRP). The aim of this study was to investigate the performance of the biomarkers serum amyloid A (SAA) and soluble vascular cell adhesion molecule-1 (VCAM-1) in this regard. Fifteen male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc for 6 h. Plasma samples were collected before, 6 and 24 h after start of exposure and biomarkers therein were measured by electrochemiluminescent assay. For each exposure, systemic concentrations of systemic SAA, but not VCAM-1, increased significantly at 24 h after exposure start compared with baseline ("copper only": P=0.0005, "zinc only": P=0.027, "copper and zinc": P=0.001). SAA showed a wider range of concentrations than did CRP and its levels increased up to 19-fold after welding fume exposure. The recognition of copper as a potential harmful component in welding fumes, also independent from zinc, deserves further consideration. SAA might represent a new sensitive biomarker for potential subclinical sterile inflammation after inhalation of copper- and/or zinc-containing welding fumes. As elevations of CRP and SAA protein have both been linked to a higher risk for cardiovascular disease, these findings might particularly be important for long-term welders.

Pathotyping and antibiotic resistance of porcine enterovirulent Escherichia coli strains from Switzerland (2014-2015).

INTRODUCTION: A total of 131 porcine E. coli were isolated in 2014 and 2015 from the gut of 115 pigs raised in Switzerland and suffering from diarrhea. The isolates were tested for antibiotic resistance, serotypes, virulence factors and genetic diversity. Serotypes were assigned by agglutination tests and virulence genes were identified by polymerase chain reaction (PCR). Antibiotic resistance profile was determined by the measurement of the MIC of 14 antibiotics and by the detection of the corresponding genes using microarray and PCR approaches. Genetic diversity was determined by repetitive palindromic PCR (rep- PCR) revealing a heterogenous population. Half of the E. coli isolates possessing virulence factors could not be assigned to any of the 19 serotypes tested, but contained toxins and adhesins similarly to the sero-typable E. coli isolates. The most prevalent E. coli serotypes found were K88ac (18%), O139:K82 (6%), O141:K85ac (5%), O108:K`V189` (5%), O119:K`V113` (3%) and O157:K`V17` (2%). The combination of toxins EAST-1, STb and LT-I and adhesin F4 characterizing ETEC was the most frequent. The shigatoxin Stx2e (STEC) and intimin Eae (EPEC) were also detected, but less frequently. Seventy percent of the isolates were resistant to at least one antibiotic and 29% were resistant to more than 3 antibiotics. Isolates exhibited resistance to tetracycline (50%) associated to resistance genes tet(A), tet(B) and tet(C), sulfamethoxazole (49%) [sul1, sul2 and sul3], trimethoprim (34%) [dfr], nalidixic acid (29%), ampicillin (26%) [blaTEM-1], gentamicin (17%) [aac(3) -IIc, aac(3) -IVa and aac(3) -VIa], chloramphenicol (17%) [catAI and catAIII], and ciprofloxacin (8%) [mutations in GyrA (S83L) and ParC (S80I)]. All isolates were susceptible to 3rd generation cephalosporins, carbapenems, colistin and tigecycline. Pathogenic E. coli isolates from pigs in Switzerland could frequently not be assigned to a known serotype even if they contained diarrhea-causing virulence factors. They also harbor resistance mechanisms conferring resistance to antibiotics which are commonly used in pig husbandry, except for colistin. A careful identification of the causative agent and antibiotic susceptibility testing is highly recommended for targeted therapy and prudent use of antibiotics.

INTRODUCTION: Dans la cadre de cette étude, on a isolé, durant les années 2014 et 2015, 131 souches d'E.coli provenant des intestins de porcs suisses souffrant de diarrhée. Ces souches ont été testées quant à leurs résistances aux antibiotiques; en outre on a déterminé leurs sérotypes, leurs facteurs de virulence et leur diversité génétique. L'attribution des isolats d'E.coli aux divers sérogroupes a été réalisée au moyen d'une séro-agglutination et les facteurs de virulence ont été déterminés par PCR. Les profils de résistance aux antibiotiques ont été déterminés par la mesure des concentrations inhibitrices minimales de 14 antibiotiques. Les gènes qui y étaient associés ont été identifiés par puces à ADN et PCR. La diversité génétique a été déterminée au moyen de PCR répétitives palindromiques (rep PCR). La moitié des isolats d'E.coli qui possédaient des facteurs de virulence n'ont pas pu être classés dans un des 19 sérotypes testés, bien qu'ils aient possédé les mêmes toxines et adhésines que les isolats qu'il a été possible de typiser. Les sérotypes les plus fréquemment trouvés étaient (18%), O139:K82 (6%), O141:K85ac (5%), O108:K`V189` (5%), O119:K`V113` (3%) et O157:K`V17` (2%). La combinaison des toxines EAST-1, STb et LT-I et de l'adhésine F4, qui est caractéristique pour les E.coli entérotoxiques (ETEC), a été le plus fréquemment trouvée. La shigatoxine Stx2e (STEC) et l'Intimin Eae (EPEC) étaient par contre plutôt rares. Les résultats des rep PCR montraient une population hétérogène. 70% des isolats présentaient une résistance face à au moins un antibiotique et 29% étaient résistants à plus de 3 antibiotiques. Les isolats montraient des résistances vis-à-vis de la tétracycline (50%) associée avec les gènes de résistance tet(A), tet(B) et tet(C), du sulfaméthoxazole (49%) [sul1, sul2 et sul3], du trimethoprime (34%) [dfr], de l'acide nalidixique (29%), de l'ampicilline (26%) [blaTEM-1], de la gentamicine (17%) [aac(3) -IIc, aac(3) -IVa et aac(3) -VIa], du chloramphenicol (17%) [catAI and catAIII] et de la ciprofloxacine (8%) [mutations dans GyrA (S83L) et ParC (S80I)]. Tous les isolats étaient sensibles aux céphalosporines de troisième génération, au carbapénèmes, à la colistine et à la tigecycline. Les E.coli pathogènes des porcs en Suisse n'ont souvent pas pu être attribués aux sérogroupes connus, bien qu'ils possèdent les facteurs de virulence causant la diarrhée. En outre on a découvert divers mécanismes de résistance contre des antibiotiques qui sont régulièrement utilisés dans la production porcine. En conséquence, une identification rigoureuse et soignée des germes responsables de maladie et un testage de la sensibilité avant traitement est de première importance.

[Fish oil in pregnancy: can it prevent asthma in children?] / Visolie tijdens de zwangerschap.

Taking fish oil supplements in the third trimester of pregnancy was associated with significantly less wheezing or asthma in the child at the age of 3-5 years, according to a randomized clinical trial by Bisgaard et al., NEJM 2017. However, the results of this study should be interpreted with caution. The primary end points were modified at a late stage in the study, and two primary end points, eczema in the first 3 years of life and allergic sensitization at 18 months of age, were demoted to secondary end points, and showed no significant effect of treatment. Furthermore, the age range for the published primary end point, persistent wheeze, differed from that in the protocol. Additional concerns include the emphasis on outcomes by omega-3 fatty acid levels in the blood, a post hoc subgroup analysis not included in the protocol. In our opinion, this study does not justify advising routine fish oil supplements in pregnancy.

[Assessing the quality of the medical learning environment, comparison of two validated Dutch questionnaires]. / Meten van de kwaliteit van de medische leeromgeving.

- Assessing the quality of the medical learning environment is an important part of the quality cycle of postgraduate medical education programmes.- The quality of the medical learning environment is primarily assessed by systematically documenting the experiences of doctors-in-training (residents).- For this purpose, several questionnaires have been developed, two of which have been specifically developed for use in the Dutch clinical learning environment.- D-RECT is a commonly-used, 50-item questionnaire (11 subscales), developed from qualitative research on the optimal learning environment for ObGyn residents.- SPEED ('Training Thermometer') is a recently developed 15-item, 3-domain (i.e., content, atmosphere and organisation of training) instrument, based on a generic theoretical framework of human interaction.- Both D-RECT and SPEED are validated instruments to be used to reliably assess the clinical learning environment for Dutch residents in postgraduate medical education programmes.

[Registration of assessments in orthopaedic residents' portfolios is falling short]. / Praktijktoetsen van aiossen onvoldoende geregistreerd.

OBJECTIVE: To evaluate of the number of registered competency assessments in the portfolios of orthopaedic residents in the Netherlands, for whom a competency-based training programme is mandatory. DESIGN: National cohort study. METHOD: We collected data regarding the registered assessments of all orthopaedic residents who finished their training between 2012-2015. We determined the number of registered assessments of 'standard orthopaedic treatments' (evaluating residents' competency in 70 different orthopaedic treatments), objective structured clinical skills evaluations (OSCEs), critically appraised topics (CATs), and 360 degree feedback appraisals. We compared the number of registered assessments in the portfolios with the minimum requirements laid down by the training curriculum. RESULTS: A total of 196 residents finished their training between 2012 and 2015. These residents finished their training with a mean (i.e., percentage of minimally required number of assessments) of 17.0 (34%) 'standard orthopaedic treatments' (level 4 or 5), 13.6 (34%) OSCEs, 2.6 (33%) CATs and 0.2 (4%) 360 degree feedback. CONCLUSION: On average, only one-third of the minimally required number of assessments were registered in the portfolios of orthopaedic residents (OSCEs and standard orthopaedic treatments level 4 or 5). These revelations show that action is needed to improve the way in which the progress of residents is monitored. These findings are going to have an effect on the new curriculum which must be more practical and less complex. Additionally, external quality control will focus more on residents at the end of their training and on the training region involved. This information may serve as a framework for postgraduate training programmes in other scientific associations which also find themselves in the same process of modernisation.

HDAC1 and HDAC2 integrate the expression of p53 mutants in pancreatic cancer.

Mutation of p53 is a frequent genetic lesion in pancreatic cancer being an unmet clinical challenge. Mutants of p53 have lost the tumour-suppressive functions of wild type p53. In addition, p53 mutants exert tumour-promoting functions, qualifying them as important therapeutic targets. Here, we show that the class I histone deacetylases HDAC1 and HDAC2 contribute to maintain the expression of p53 mutants in human and genetically defined murine pancreatic cancer cells. Our data reveal that the inhibition of these HDACs with small molecule HDAC inhibitors (HDACi), as well as the specific genetic elimination of HDAC1 and HDAC2, reduce the expression of mutant p53 mRNA and protein levels. We further show that HDAC1, HDAC2 and MYC directly bind to the TP53 gene and that MYC recruitment drops upon HDAC inhibitor treatment. Therefore, our results illustrate a previously unrecognized class I HDAC-dependent control of the TP53 gene and provide evidence for a contribution of MYC. A combined approach targeting HDAC1/HDAC2 and MYC may present a novel and molecularly defined strategy to target mutant p53 in pancreatic cancer.

IL-6, a central acute-phase mediator, as an early biomarker for exposure to zinc-based metal fumes.

AIMS: Systemic C-reactive protein (CRP) increases 1day after short-term inhalation of welding fumes containing zinc and/or copper. The aim of the current study was to find further, possibly earlier systemic biomarkers after inhalation of different welding fumes containing zinc and traces of aluminum, with or without copper, as these metal combinations become more common in modern joining technology. METHODS: The study group consisted of 15 non-smoking male volunteers with healthy lung function data and without any occupational metal fume exposure. On 4 different exposure days, the members of the study group were exposed under controlled conditions to ambient air or 3 different welding fumes for 6h. Spirometric and impulse oscillometric measurements and differential blood counts were performed and serum samples were collected before exposure and 6, 10 and 29h after start of exposure. The biomarker concentrations in serum were measured by electrochemiluminescent assays. RESULTS: Systemic increases of IL-6 peaked significantly at 10h compared to baseline ("ZincZinc": P=0.0005 (median increase (m. incr.)=1.36pg/mL); "ZincAlu": P=0.0012 (m. incr.=1.48pg/mL); "AluBronze": P=0.0005 (m. incr.=2.66pg/mL)). At 29h, CRP and serum amyloid A (SAA) increased distinctively ("ZincZinc": P=0.032 (m. incr.=0.65µg/mL) [CRP], 0.077 (m. incr.=0.61µg/mL) [SAA]; "ZincAlu": P=0.001 (m. incr.=1.15µg/mL) [CRP], 0.0024 (m. incr.=0.94µg/mL) [SAA]; "AluBronze": P=0.002 (m. incr.=2.5µg/mL) [CRP], 0.002 (m. incr.=0.97µg/mL) [SAA]). The median increases of CRP and IL-6 were most pronounced for the welding fume which contained besides zinc also copper (AluBronze). For differentiating AluBronze from control exposure, receiver operating characteristic (ROC) curve analysis was performed and the area under the ROC curve (AUC) for the IL-6 increases (10h versus 0h) was 0.931. The additional inflammatory mediators [vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), interferon-γ (IFN-γ), cell counts] and the lung function parameters did not show any significant changes after exposure. CONCLUSIONS: Consistent with its role of the mediation of the acute-phase response, systemic increases of IL-6 after welding fume exposure peak at 10h before the increases of the acute-phase reactants CRP and SAA at 29h. IL-6 may represent a highly sensitive and early biomarker for the exposure to metal fumes containing zinc and copper. As IL-6, CRP and SAA are independent, strong risk markers for future cardiovascular diseases, these data may particularly be important for long-term welders with respect to their cardiovascular health.