Phenotypic and Molecular Characterization of an Enterobacter ludwigii Clinical Isolate Carrying a Plasmid-Mediated blaIMI-6 Gene.

We report a plasmid-encoded IMI-6 carbapenemase in a clinical isolate of Enterobacter ludwigii from Spain. The isolate belongs to ST641 and was susceptible to expanded-spectrum cephalosporins and resistant to carbapenems. The modified carbapenem inactivation method (mCIM) test was positive, but ß-Carba was negative. Whole-genome sequencing identified the blaIMI-6 gene located in a conjugative IncFIIY plasmid and associated with the LysR-like regulator imiR. Both genes were bracketed by an ISEclI-like insertion sequence and a putatively defective ISEc36 insertion sequence. IMPORTANCE IMI carbapenemases confer an unusual resistance pattern of susceptibility to broad-spectrum cephalosporins and piperacillin-tazobactam but decreased susceptibility to carbapenems, which may make them difficult to detect in routine practice. Commercially available molecular methods for the detection of carbapenemases in clinical laboratories do not usually include blaIMI genes, which could contribute to the hidden dissemination of bacteria producing these enzymes. Techniques should be implemented to detect minor carbapenemases that are not very frequent in our environment and control their dissemination.

Community-acquired bacteraemia by Klebsiella pneumoniae producing KPC-3 and resistant to ceftazidime/avibactam.

OBJECTIVES: To describe the clinical and microbiological features of a case of community-acquired infection by KPC-producing K. pneumoniae (KPCKP) resistant to ceftazidime/avibactam (CAZ-AVI). METHODS: Identification of microorganisms was performed with MALDI Biotyper CA System (BrukerDaltonics, Madrid, Spain). Antimicrobial susceptibility testing was performed using Sensitre EURGNCOL panels (Thermo Fisher Scientific, Madrid, Spain) and gradient strips (Etest, bioMérieux, Madrid, Spain) in the case of CAZ-AVI, using EUCAST breakpoints for interpretation. Whole genome sequencing of blood culture and rectal swab isolates was performed using the Illumina NovaSeq 6000 sequencing system, with 2 × 150-bp paired-end reads (Illumina, Inc.). RESULTS: Blood culture and rectal swab KPCKP isolates were resistant to carbapenems and to CAZ-AVI. The blood culture isolate showed susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX), but the rectal swab culture isolate was resistant to this antibiotic. Both isolates belonged to clonal lineage ST512, harboured a single copy of blaKPC-3 gene, and showed 16 single nucleotide polymorphisms (SNP) between them and 38 SNPs with regard to the first KPC-3 producing K. pneumoniae isolated in our hospital in an initial outbreak in 2012. Genome-wide resistome analysis revealed the presence of a IncFIB(K) plasmid harbouring sul1 and dfrA12 genes only in the rectal swab culture isolate, which may explain its resistance to TMP-SMX. CONCLUSIONS: Resistance to ceftazidime-avibactam is an emerging nosocomial problem. This case shows that CAZ-AVI-resistant KPCKP strains may disseminate into the community and cause serious infections.

Mecanismos de resistencia en bacterias gramnegativas / Resistance mechanisms in Gram-negative bacteria

Los Enterobacterales resistentes a carbapenémicos o productores de betalactamasas de espectro extendido (BLEE) y los no fermentadores resistentes a carbapenémicos presentan resistencia a muchos de los antimicrobianos comúnmente empleados en la práctica clínica, y han sido reconocidos por la Organización Mundial de la Salud como una prioridad crítica para el desarrollo de nuevos antimicrobianos. En esta revisión se abordarán los principales mecanismos de resistencia de los Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii y Stenotrophomonas maltophilia a betalactámicos, quinolonas, aminoglucósidos y polimixinas. Se presentará información actualizada sobre la importancia en la resistencia de mecanismos de modificación de antimicrobianos (incluyendo betalactamasas de claseC de espectro extendido, carbapenemasas y enzimas modificadoras de aminoglucósidos), alteraciones de la permeabilidad por trastornos en la expresión de porinas o del lipopolisacárido, producción de bombas de expulsión activa, alteraciones de la diana o protección de la misma y expresión de sistemas de doble componente (AU)

Enterobacterales resistant to carbapenems or producing extended-spectrum β-lactamases (ESBL) and non-fermenters resistant to carbapenems present resistance to many of the antimicrobials commonly used in clinical practice, and have been recognized by the World Health Organization as a critical priority for the development of new antimicrobials. In this review, the main mechanisms of resistance of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia to β-lactams, quinolones, aminoglycosides and polymyxins will be addressed. Updated information will be presented on the importance in resistance of antimicrobial modification mechanisms (including classC or extended-spectrum β-lactamases, carbapenemases and aminoglycoside-modifying enzymes), permeability alterations due to porin or lipopolysaccharide expression disorders, production of active efflux pumps, target alterations or protection, and expression of two-component systems (AU)

Resistance mechanisms in Gram-negative bacteria.

Enterobacterales resistant to carbapenems or producing extended-spectrum ß-lactamases (ESBL) and non-fermenters resistant to carbapenems present resistance to many of the antimicrobials commonly used in clinical practice, and have been recognized by the World Health Organization as a critical priority for the development of new antimicrobials. In this review, the main mechanisms of resistance of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia to ß-lactams, quinolones, aminoglycosides and polymyxins will be addressed. Updated information will be presented on the importance in resistance of antimicrobial modification mechanisms (including class C or extended-spectrum ß-lactamases, carbapenemases and aminoglycoside-modifying enzymes), permeability alterations due to porin or lipopolysaccharide expression disorders, production of active efflux pumps, target alterations or protection, and expression of two-component systems.

In vivo selection of KPC-94 and KPC-95 in Klebsiella pneumoniae isolates from patients treated with ceftazidime/avibactam.

Ceftazidime/avibactam (CZA) is used to treat infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp). Resistance to CZA is commonly related to point mutations in the blaKPC gene. Here we describe the in vivo emergence of CZA resistance in clinical isolates of KPC-Kp from four patients treated with this combination therapy. Four pre-therapy and five post-therapy KPC-Kp isolates were examined. Antibiogram (microdilution and gradient strips) and whole-genome sequencing were performed. The role of KPC mutations was validated by cloning blaKPC genes into competent Escherichia coli. All KPC-Kp isolates recovered before treatment with CZA were susceptible to CZA and produced KPC-3. Five KPC-Kp isolates recovered after treatment were resistant to this combination. Three post-therapy isolates from two patients produced KPC-31 (D179Y mutation). Additionally, we identified the novel substitution LN169-170H (KPC-94) in one isolate, and the combination of two independently described mutations, D179Y and A172T (KPC-95), in another isolate. All KPC-Kp isolates belonged to sequence type 512 (ST512). All CZA-resistant isolates with blaKPC variants had restoration of carbapenem susceptibility. In conclusion, resistance to CZA was related to blaKPC mutations, including the new KPC-94 and KPC-95 alleles, which do not cause carbapenem resistance.

Development of an Anti-Acinetobacter baumannii Biofilm Phage Cocktail: Genomic Adaptation to the Host.

The need for alternatives to antibiotic therapy due to the emergence of multidrug resistant bacteria (MDR), such as the nosocomial pathogen Acinetobacter baumannii, has led to the recovery of phage therapy. In addition, phages can be combined in cocktails to increase the host range. In this study, the evolutionary mechanism of adaptation was utilized in order to develop a phage adapted to A. baumannii, named phage Ab105-2phiΔCI404ad, from a mutant lytic phage, Ab105-2phiΔCI, previously developed by our group. The whole genome sequence of phage Ab105-2phiΔCI404ad was determined, showing that four genomic rearrangements events occurred in the tail morphogenesis module affecting the ORFs encoding the host receptor binding sites. As a consequence of the genomic rearrangements, 10 ORFs were lost and four new ORFs were obtained, all encoding tail proteins; two inverted regions were also derived from these events. The adaptation process increased the host range of the adapted phage by almost 3-fold. In addition, a depolymerase-expressing phenotype, indicated by formation of a halo, which was not observed in the ancestral phage, was obtained in 81% of the infected strains. A phage cocktail was formed by combining this phage with the A. baumannii phage vB_AbaP_B3, known to express a depolymerase. Both the individual phages and the phage cocktail showed strong antimicrobial activity against 5 clinical strains and 1 reference strain of A. baumannii tested. However, in all cases resistance to the bacterial strains was also observed. The antibiofilm activity of the individual phages and the cocktail was assayed. The phage cocktail displayed strong antibiofilm activity.

miR-19b-3p and miR-20a-5p are associated with the levels of antiphospholipid antibodies in patients with antiphospholipid syndrome.

Monocytes play a key role in pathophysiology of antiphospholipid syndrome (APS), nevertheless it is unclear if microRNA expression is associated with particular APS features. Identify whether miR-19b-3p and miR-20a-5p expression in monocytes are associated with hallmarks of the APS. Fifty-seven APS patients and 18 healthy controls were studied. Expression of miR-19b-3p and miR-20a-5p was measured in monocytes by RT-qPCR. Both miR-19b-3p (AUC = 0.835, 95% CI 0.733-0.938; P < 0.001) and miR-20a-5p (AUC = 0.857, 0.757-0.957; P < 0.001) discriminated APS patients from healthy individuals. A cut-off point of 1.98 for miR-19-3p and 2.18 for miR-20a-5p showed that APS patients with low microRNA expression had higher levels of IgM and IgG anticardiolipin antibodies than patients with high microRNA expression. In addition, APS patients with low microRNA expression had higher IgG anti-ß2 glycoprotein I antibody levels than their counterparts with high microRNA expression. Finally, miR-19b-3p and miR-20a-5p expression levels were significantly higher in APS patients using oral anticoagulants. Monocyte expression of miR-19b-3p and miR-20a-5p is low in APS, and patients with the lowest microRNA expression presented the highest levels of antiphospholipid antibodies.

Working status of Spanish pediatric surgeons. / Situación de los profesionales de cirugía pediátrica en España.

OBJECTIVE: To analyze work, demographic, and social parameters in order to learn about the working status of pediatric surgeons in Spain. MATERIAL AND METHODS: A survey inspired in job satisfaction models and designed by the authors was performed. It was an observational, descriptive, cross-border online survey intended for pediatric surgeons from the Spanish Society of Pediatric Surgery (SECIPE). RESULTS: Of the 290 SECIPE pediatric surgeons, 133 responded to the survey (45.8% response rate), of whom 49.6% were 30-39 years old. The number of male and female respondents was virtually the same. 69% of respondents devoted 75-100% of their working hours to healthcare, 89.4% devoted 0-25% to research, and 80% devoted 0-25% to teaching. The survey demonstrated job satisfaction in terms of colleagues, healthcare role, professional development expectations, and social consideration. However, respondents showed disconformity with their pay, the time devoted to research and teaching, and their relationship with the executive board. CONCLUSION: This study sheds light on the Spanish professionals' working status, which can help identify measures for improvement. The survey shows widespread disconformity with the short time devoted to research, and little satisfaction with teaching. Most of the working hours are devoted to clinical practice, with poor pay satisfaction, which can contribute to dissatisfaction in the development of healthcare activity.

OBJETIVO: Analizar parámetros sociolaborales y sociodemográficos para conocer la situación de los cirujanos pediátricos en España. MATERIAL Y METODOS: Se realizó una encuesta de elaboración propia inspirada en modelos de satisfacción laboral. Es un estudio observacional, descriptivo y transversal, realizado online a los cirujanos pediátricos pertenecientes a la Sociedad Española de Cirugía Pediátrica (SECIPE). RESULTADOS: De los 290 cirujanos pediátricos de la SECIPE, 133 contestaron a la encuesta (tasa de respuesta de 45,8%). De estos, el 49,6% tienen entre 30-39 años, habiendo casi igualdad entre hombres y mujeres. El 69% de los encuestados dedican entre el 75 y el 100% de su tiempo de trabajo a la asistencia, el 89,4% dedica entre 0-25% a la investigación y el 80% entre 0 y 25 % a la docencia. Los resultados mostraron satisfacción laboral tanto en relación con el equipo de trabajo como con la calidad asistencial, las posibilidades de desarrollo profesional o la consideración social. Sin embargo los encuestados mostraron su disconformidad con respecto al sueldo, al tiempo dedicado a la investigación y a la docencia, y a la relación con la dirección. CONCLUSION: Este estudio permite conocer la situación laboral de los profesionales en España, lo que puede ayudar a identificar medidas de mejora. La encuesta señala un descontento generalizado con el escaso tiempo dedicado a la investigación y poca satisfacción en el trabajo docente. La mayor parte del tiempo se dedica a la práctica clínica, existiendo baja satisfacción salarial, circunstancias que pueden contribuir a la insatisfacción en el desarrollo de la actividad asistencial.

Situación de los profesionales de cirugía pediátrica en España / Working status of Spanish pediatric surgeons

OBJETIVO: Analizar parámetros sociolaborales y sociodemográficos para conocer la situación de los cirujanos pediátricos en España. MATERIAL Y MÉTODOS: Se realizó una encuesta de elaboración propia inspirada en modelos de satisfacción laboral. Es un estudio observacional, descriptivo y transversal, realizado online a los cirujanos pediátricos pertenecientes a la Sociedad Española de Cirugía Pediátrica (SECIPE). RESULTADOS: De los 290 cirujanos pediátricos de la SECIPE, 133 contestaron a la encuesta (tasa de respuesta del 45,8%). De estos, el 49,6% tienen entre 30-39 años, habiendo casi igualdad entre hombres y mujeres. El 69% de los encuestados dedican entre el 75 y el 100% de su tiempo de trabajo a la asistencia, el 89,4% dedica entre 0-25% a la investigación y el 80% entre 0 y 25 % a la docencia. Los resultados mostraron satisfacción laboral, tanto en relación con el equipo de trabajo como con la calidad asistencial, las posibilidades de desarrollo profesional o la consideración social. Sin embargo, los encuestados mostraron su disconformidad con respecto al sueldo, al tiempo dedicado a la investigación y a la docencia, y a la relación con la dirección. CONCLUSIÓN: Este estudio permite conocer la situación laboral de los profesionales en España, lo que puede ayudar a identificar medidas de mejora. La encuesta señala un descontento generalizado con el escaso tiempo dedicado a la investigación y poca satisfacción en el trabajo docente. La mayor parte del tiempo se dedica a la práctica clínica, existiendo baja satisfacción salarial, circunstancias que pueden contribuir a la insatisfacción en el desarrollo de la actividad asistencial

OBJECTIVE: To analyze work, demographic, and social parameters in order to learn about the working status of pediatric surgeons in Spain. MATERIALS AND METHODS: A survey inspired in job satisfaction models and designed by the authors was performed. It was an observational, descriptive, cross-border online survey intended for pediatric surgeons from the Spanish Society of Pediatric Surgery (SECIPE). RESULTS: Of the 290 SECIPE pediatric surgeons, 133 responded to the survey (45.8% response rate), of whom 49.6% were 30-39 years old. The number of male and female respondents was virtually the same. 69% of respondents devoted 75-100% of their working hours to healthcare, 89.4% devoted 0-25% to research, and 80% devoted 0-25% to teaching. The survey demonstrated job satisfaction in terms of colleagues, healthcare role, professional development expectations, and social consideration. However, respondents showed disconformity with their pay, the time devoted to research and teaching, and their relationship with the executive board. CONCLUSION: This study sheds light on the Spanish professionals' working status, which can help identify measures for improvement. The survey shows widespread disconformity with the short time devoted to research, and little satisfaction with teaching. Most of the working hours are devoted to clinical practice, with poor pay satisfaction, which can contribute to dissatisfaction in the development of healthcare activity

Efficacy of endoscopic removal in the treatment of subglottic ductal cysts. / Eficacia de la escisión endoscópica en el tratamiento de los quistes ductales subglóticos.

INTRODUCTION: Subglottic cyst is a rare cause of airway obstruction, and there is a lack of evidence about the best treatment in the literature. This report describes our experience with endoscopic removal. MATERIAL AND METHODS: A retrospective study of all patients undergoing endoscopic removal of subglottic cyst at our healthcare facility between 2014 and 2019 was performed. Clinic and demographic data regarding gestational age, intubation, comorbidities, surgical procedures, first symptoms, endoscopic findings, treatment, and follow-up were collected. RESULTS: Four patients were identified. Two out of four (50%) were preterm, and all patients were intubated during their neonatal period. Median age and weight at diagnosis were 6.5 months (6-8) and 5.9 kg (3.6-7). Median time between last intubation and diagnosis was 119.5 days (71-171). Biphasic stridor and progressive respiratory distress were the most common clinical symptoms. Airway obstruction of at least 50% was found during upper airway endoscopy in all patients. Endoscopic removal was performed as a first-line treatment in 3 patients, and as a second-line treatment in 1 patient. Median intubation time after treatment and hospital stay were 13.5 hours (0-48) and 7 days (6-9). All four patients are free of disease, with a median follow-up of 17.5 months (6-42). CONCLUSION: Subglottic cyst is a rare cause of post-extubation stridor. Endoscopic removal seems to be a feasible and effective treatment with a low recurrence rate.

INTRODUCCION: Los quistes ductales subglóticos adquiridos (QDSA) son una causa rara de obstrucción de la vía aérea, sin consenso en la literatura en cuanto al tratamiento más eficaz. Presentamos nuestra experiencia en el tratamiento de los QDSA. MATERIAL Y METODOS: Estudio retrospectivo de los pacientes tratados en nuestro centro por QDSA en los últimos 5 años. Se recogieron los antecedentes de intubación, la clínica presentada, el tratamiento realizado, la evolución postquirúrgica, el seguimiento en consulta y los controles endoscópicos. RESULTADOS: Se identificaron 4 pacientes, con unas medianas de edad y peso de 6,5 meses (6-8) y 5,9 kg (3,6-7), respectivamente. Todos presentaron antecedentes de intubación por intervenciones quirúrgicas, siendo prematuros 2 de ellos. La mediana entre la última intubación y el diagnóstico fue de 119,5 días (71-171). La clínica consistió en estridor bifásico con mejoría postural presentando una ocupación de la luz traqueal de más del 50% en la endoscopia diagnóstica. Se realizó escisión endoscópica (EE) al diagnóstico en 3 de los pacientes y como técnica de rescate en el cuarto por recidiva tras tratamiento con drenaje y dilatación con balón. La mediana de tiempo de intubación postquirúrgico fue de 13,5 horas (0-48) y la estancia hospitalaria de 7 días (6-9). Tras un seguimiento mediano de 17,5 meses (6-42) no se ha presentado ninguna recidiva. CONCLUSION: Los QDSA son una causa poco frecuente de estridor post-extubación. La EE permite un tratamiento eficaz con baja tasa de recidiva.

Eficacia de la escisión endoscópica en el tratamiento de los quistes ductales subglóticos / Efficacy of endoscopic removal in the treatment of subglottic ductal cysts

Introducción: Los quistes ductales subglóticos adquiridos (QDSA) son una causa rara de obstrucción de la vía aérea, sin consenso en la literatura en cuanto al tratamiento más eficaz. Presentamos nuestra experiencia en el tratamiento de los QDSA. Material y métodos: Estudio retrospectivo de los pacientes trata-dos en nuestro centro por QDSA en los últimos 5 años. Se recogieron los antecedentes de intubación, la clínica presentada, el tratamiento realizado, la evolución postquirúrgica, el seguimiento en consulta y los controles endoscópicos. Resultados: Se identificaron 4 pacientes, con unas medianas de edad y peso de 6,5 meses (6-8) y 5,9 kg (3,6-7), respectivamente. Todos presentaron antecedentes de intubación por intervenciones quirúrgicas, siendo prematuros 2 de ellos. La mediana entre la última intubación y el diagnóstico fue de 119,5 días (71-171). La clínica consistió en estridor bifásico con mejoría postural presentando una ocupación de la luz traqueal de más del 50% en la endoscopia diagnóstica. Se realizó escisión endoscópica (EE) al diagnóstico en 3 de los pacientes y como técnica de rescate en el cuarto por recidiva tras tratamiento con drenaje y dilatación con balón. La mediana de tiempo de intubación postquirúrgico fue de 13,5 horas (0-48) y la estancia hospitalaria de 7 días (6-9). Tras un seguimiento mediano de 17,5 meses (6-42) no se ha presentado ninguna recidiva. Conclusión: Los QDSA son una causa poco frecuente de estridor post-extubación. La EE permite un tratamiento eficaz con baja tasa de recidiva

Introduction: Subglottic cyst is a rare cause of airway obstruction, and there is a lack of evidence about the best treatment in the literature. This report describes our experience with endoscopic removal. Materials and methods: A retrospective study of all patients un-dergoing endoscopic removal of subglottic cyst at our healthcare facility between 2014 and 2019 was performed. Clinic and demographic data regarding gestational age, intubation, comorbidities, surgical procedures, first symptoms, endoscopic findings, treatment, and follow-up were collected. Results: Four patients were identified. Two out of four (50%) were preterm, and all patients were intubated during their neonatal period. Median age and weight at diagnosis were 6.5 months (6-8) and 5.9 kg (3.6-7). Median time between last intubation and diagnosis was 119.5 days (71-171). Biphasic stridor and progressive respiratory distress were the most common clinical symptoms. Airway obstruction of at least 50% was found during upper airway endoscopy in all patients. Endoscopic removal was performed as a first-line treatment in 3 patients, and as a second-line treatment in 1 patient. Median intubation time after treatment and hospital stay were 13.5 hours (0-48) and 7 days (6-9). All four pa-tients are free of disease, with a median follow-up of 17.5 months (6-42). Conclusion: Subglottic cyst is a rare cause of post-extubation stri-dor. Endoscopic removal seems to be a feasible and effective treatment with a low recurrence rate

Weighting the impact of virulence on the outcome of Pseudomonas aeruginosa bloodstream infections.

OBJECTIVES: We assessed the association between the lethality of Pseudomonas aeruginosa in a Caenorhabditis elegans model and outcomes of P. aeruginosa bloodstream infections. METHODS: A total of 593 P. aeruginosa bloodstream isolates recovered from a prospective Spanish multicentre study were analysed. Clinical variables, susceptibility profiles and Type III Secretion System (TTSS) genotypes (exoU/exoS genes) were available from previous studies. A C. elegans virulence score (CEVS) was used, classifying the isolates into high (CEVS 4-5), intermediate (CEVS 3) and low (CEVS 1-2) virulence. The main outcome analysed was 30-day mortality. RESULTS: Up to 75% (446/593) of the isolates showed a high-virulence phenotype, and 17% (101/593) a low-virulence one. No association between virulence phenotype and the main outcome variable (30-day mortality) was found (29/101 (28.7%) versus 127/446 (28.5%), p 1). However, an inverse association between C. elegans virulence and multidrug-resistant and extensively drug-resistant profiles was documented (OR 0.655 (95% CI 0.571-0.751) and OR 0.523 (95% CI 0.436-0.627), p <0.001, respectively), whereas the exoU genotype was significantly more frequent among isolates showing high virulence (10/101 (9.9%) versus 112/446 (25.1%), p <0.001). Moreover, although significance was not reached, strains showing a high-virulence phenotype tended to be associated with community-acquired infections (1/101 (1%) versus 25/446 (5.6%), p 0.065), whereas low-virulence phenotypes tended to be associated with a higher illness severity (such as higher median Pitt score: 2 (1-4) versus 1 (0-3), p 0.036, or initial multiorgan dysfunction: 17/101 (16.8%) versus 41/446 (9.2%), p 0.024), with some underlying conditions (such as chronic renal failure 24/101 (23.8%) versus 59/446 (13.2%), p 0.013), and with the respiratory source of infections (17/101 (16.8%) versus 45/446 (10.1%), p 0.058). CONCLUSIONS: Our results indicate that the P. aeruginosa virulence phenotype in a C. elegans model correlates with virulence genotype (TTSS) and resistance profile, but it is a poor prognostic marker of mortality in bloodstream infections.

[Neutrophil-to-lymphocyte ratio as a predictor of peritonitis in acute appendicitis in children]. / Índice neutrófilo-linfocito como predictor de peritonitis en apendicitis aguda en niños.

AIM OF THE STUDY: The neutrophil-to-lymphocyte ratio (NLR) has been postulated as an inflammatory marker in several abdominal pathologies such as acute appendicitis (AA). However, there are few studies that determine its association with the degree of severity of AA. This is the first study that analyzes the usefulness of NLR as a predictor of peritonitis in children with AA. METHODS: Retrospective observational study in patients treated of AA during the years 2017 and 2018. They were divided into two groups according to the intraoperative diagnosis (uncomplicated AA and AA with peritonitis). Demographic and analytical variables were analyzed. The NLR was defined as the quotient between the absolute values of neutrophils and lymphocytes. The sensitivity and specificity for the diagnosis of peritonitis of different analytical parameters were determined by ROC curves. RESULTS: A total of 398 patients were included (uncomplicated AA n=342 and AA with peritonitis n=56), with a mean age of 10.5±2.9 years. The NLR had an area under the curve (AUC) of 0.78, significantly higher than the determination of leukocytes (AUC 0.71, p=0.002) and of neutrophils (AUC 0.74, p=0.009). No differences were observed when compared to the determination of C-reactive protein (AUC 0.79, p=0.598). A cut-off point of NLR>8.75 was estimated with a sensitivity and specificity of 75.0 and 72.2% respectively. CONCLUSIONS: The NLR is a useful tool to predict the presence of peritonitis in AA, and could be considered an alternative to other higher cost determinations such as C-reactive protein.

INTRODUCCION: El índice neutrófilo-linfocito (INL) se ha postulado como marcador inflamatorio en distintas patologías abdominales como la apendicitis aguda (AA). Sin embargo, existen pocos estudios que determinen su asociación con el grado de severidad de la AA. Este es el primer estudio que analiza la utilidad del INL como factor predictor de peritonitis en la AA en niños. MATERIAL Y METODOS: Estudio observacional retrospectivo en pacientes intervenidos de AA durante los años 2017 y 2018. Se distribuyeron en dos grupos según el diagnóstico intraoperatorio (AA no complicada y AA con peritonitis). Se analizaron variables demográficas y analíticas. Se definió el INL como el cociente entre los valores absolutos de neutrófilos y linfocitos. Se determinó mediante curvas ROC la sensibilidad y especificidad para el diagnóstico de peritonitis de distintos parámetros analíticos. RESULTADOS: Se incluyeron un total de 398 pacientes (AA no complicada n= 342 y AA con peritonitis n=56), con una edad media de 10,5±2,9 años. El INL presentó un área bajo la curva (AUC) de 0,78, significativamente superior a la determinación de leucocitos (AUC 0,71; p=0,002) y de neutrófilos (AUC 0,74; p=0,009). No se observaron diferencias al compararlo con la determinación de la proteína C reactiva (AUC 0,79; p=0,598). Se estimó el punto de corte de INL>8,75 con una sensibilidad y especificidad de 75,0 y 72,2% respectivamente. CONCLUSION: El INL se postula como una herramienta útil para predecir la presencia de peritonitis en AA, y podría considerarse una alternativa a otras determinaciones de mayor coste como la proteína C reactiva.

Índice neutrófilo-linfocito como predictor de peritonitis en apendicitis aguda en niños / Neutrophil-to-lymphocyte ratio as a predictor of peritonitis in acute appendicitis in children

Introducción. El índice neutrófilo-linfocito (INL) se ha postulado como marcador inflamatorio en distintas patologías abdominales como la apendicitis aguda (AA). Sin embargo, existen pocos estudios que determinen su asociación con el grado de severidad de la AA. Este es el primer estudio que analiza la utilidad del INL como factor predictor de peritonitis en la AA en niños. Material y métodos. Estudio observacional retrospectivo en pacientes intervenidos de AA durante los años 2017 y 2018. Se distribuyeron en dos grupos según el diagnóstico intraoperatorio (AA no complicada y AA con peritonitis). Se analizaron variables demográficas y analíticas. Se definió el INL como el cociente entre los valores absolutos de neutrófilos y linfocitos. Se determinó mediante curvas ROC la sensibilidad y especificidad para el diagnóstico de peritonitis de distintos parámetros analíticos. Resultados. Se incluyeron un total de 398 pacientes (AA no complicada n= 342 y AA con peritonitis n=56), con una edad media de 10,5±2,9 años. El INL presentó un área bajo la curva (AUC) de 0,78, significativamente superior a la determinación de leucocitos (AUC 0,71; p=0,002) y de neutrófilos (AUC 0,74; p=0,009). No se observaron diferencias al compararlo con la determinación de la proteína C reactiva (AUC 0,79; p=0,598). Se estimó el punto de corte de INL>8,75 con una sensibilidad y especificidad de 75,0 y 72,2% respectivamente. Conclusión. El INL se postula como una herramienta útil para predecir la presencia de peritonitis en AA, y podría considerarse una alternativa a otras determinaciones de mayor coste como la proteína C reactiva

Aim of the study. The neutrophilto-lymphocyte ratio (NLR) has been postulated as an inflammatory marker in several abdominal pathologies such as acute appendicitis (AA). However, there are few studies that determine its association with the degree of severity of AA. This is the first study that analyzes the usefulness of NLR as a predictor of peritonitis in children with AA. Methods. Retrospective observational study in patients treated of AA during the years 2017 and 2018. They were divided into two groups according to the intraoperative diagnosis (uncomplicated AA and AA with peritonitis). Demographic and analytical variables were analyzed. The NLR was defined as the quotient between the absolute values of neutrophils and lymphocytes. The sensitivity and specificity for the diagnosis of peritonitis of different analytical parameters were determined by ROC curves. Results. A total of 398 patients were included (uncomplicated AA n=342 and AA with peritonitis n=56), with a mean age of 10.5±2.9 years. The NLR had an area under the curve (AUC) of 0.78, significantly higher than the determination of leukocytes (AUC 0.71, p=0.002) and of neutrophils (AUC 0.74, p=0.009). No differences were observed when compared to the determination of C-reactive protein (AUC 0.79, p=0.598). A cut-off point of NLR>8.75 was estimated with a sensitivity and specificity of 75.0 and 72.2% respectively. Conclusions. The NLR is a useful tool to predict the presence of peritonitis in AA, and could be considered an alternative to other higher cost determinations such as C-reactive protein

[Inferior vena cava compression in children with pectus excavatum]. / Compresión de la vena cava inferior en niños con pectus excavatum.

INTRODUCTION: In severe cases of pectus excavatum (PE) the sternal depression may cause distortion of the cardiac chambers and great vessels. The aim of our study was to determine if the sternal impingement causes significant inferior vena cava (IVC) compression. METHODS: Retrospective study of patients with severe PE assessed between 2015-2017. The antero-posterior (AP) and transverse diameters of the suprahepatic IVC were measured on a cardiac-MRI at the level of the diaphragmatic hiatus. Results were compared with patients that had a thoracic image study performed for other causes, adjusting for age and sex. RESULTS: Among the 81 patients, 28 cases and 53 controls, 63% were males and had a mean age of 12.9±0.5 yrs. Significant differences were found between groups in both AP and transverse diameter of the IVC: 13.3±0.75 mm vs. 15.8±0.76 mm (p=0.001) and 28.8±1.34 mm vs. 27.1±0.89mm (p=0.045) respectively. After adjusting for age and sex, these differences were only statistically significant for AP IVC diameter in males 12.7±0.5 mm (95% CI 11.66-13.79 mm) vs. 16.6±0.5 mm (95% CI 15.69-17.56 mm) (p=0.000). The Pearson correlation coefficient for the Haller index was r=0.471 (p=0.01). CONCLUSION: Male patients with severe sternal depression show changes in the IVC diameter that may correspond to compression. These changes are correlated with the severity of the deformity and can justify certain clinical symptoms and cardiac function abnormalities in patients with severe PE.

INTRODUCCION: En casos graves de pectus excavatum (PE), el hundimiento esternal ocasiona distorsión del corazón y grandes vasos. Nuestro propósito fue determinar si existe compresión de la vena cava inferior (VCI) en estos pacientes. METODOS: Estudio retrospectivo de pacientes con PE grave valorados entre 2015 y 2017. Se efectuaron mediciones del diámetro anteroposterior (AP) y transverso de la VCI suprahepática a su paso por el hiato diafragmático en imágenes de RM-cardiaca. Estas se compararon con las medidas de pacientes a los que se les realizó una RM o TC por otro motivo, ajustando los datos para edad y sexo. RESULTADOS: De los 81 pacientes, 28 casos y 53 controles, el 63% fueron varones con una edad media de 12,9±0,5 años. Se identificaron diferencias significativas entre los grupos, tanto del diámetro AP como del transverso: 13,3±0,75 mm vs. 15,8±0,76 mm (p=0,001) y 28,8±1,34 mm vs. 27,1±0,89 mm (p=0,045), respectivamente. Tras ajustar los datos para edad y sexo, estas diferencias solo fueron significativas para el diámetro AP de la VCI en hombres: 12,7±0,5 mm (IC95% 11,66-13,79 mm) vs. 16,6±0,5 mm (IC95% 15,69-17,56 mm) (p=0,000). El coeficiente de correlación de Pearson del diámetro transverso de la VCI con el índice de Haller fue r=0,471 (p=0,01). CONCLUSION: Los varones con un hundimiento esternal grave asocian alteraciones en el diámetro de la VCI que pueden indicar compresión de la misma. Estos cambios se correlacionan con la gravedad del PE y podrían justificar algunos síntomas y alteraciones cardiovasculares encontradas en estos pacientes.

Compresión de la vena cava inferior en niños con pectus excavatum / Inferior vena cava compression in children with pectus excavatum

Introducción: En casos graves de pectus excavatum (PE), el hundimiento esternal ocasiona distorsión del corazón y grandes vasos. Nuestro propósito fue determinar si existe compresión de la vena cava inferior (VCI) en estos pacientes. Métodos: Estudio retrospectivo de pacientes con PE grave valorados entre 2015 y 2017. Se efectuaron mediciones del diámetro anteroposterior (AP) y transverso de la VCI suprahepática a su paso por el hiato diafragmático en imágenes de RM-cardiaca. Estas se compararon con las medidas de pacientes a los que se les realizó una RM o TC por otro motivo, ajustando los datos para edad y sexo. Resultados: De los 81 pacientes, 28 casos y 53 controles, el 63% fueron varones con una edad media de 12,9±0,5 años. Se identificaron diferencias significativas entre los grupos, tanto del diámetro AP como del transverso: 13,3±0,75 mm vs. 15,8±0,76 mm (p=0,001) y 28,8±1,34 mm vs. 27,1±0,89 mm (p=0,045), respectivamente. Tras ajustar los datos para edad y sexo, estas diferencias solo fueron significativas para el diámetro AP de la VCI en hombres: 12,7±0,5 mm (IC95% 11,66-13,79 mm) vs. 16,6±0,5 mm (IC95% 15,69-17,56 mm) (p=0,000). El coeficiente de correlación de Pearson del diámetro transverso de la VCI con el índice de Haller fue r=0,471 (p=0,01). Conclusión: Los varones con un hundimiento esternal grave asocian alteraciones en el diámetro de la VCI que pueden indicar compresión de la misma. Estos cambios se correlacionan con la gravedad del PE y podrían justificar algunos síntomas y alteraciones cardiovasculares encontradas en estos pacientes

Introduction: In severe cases of pectus excavatum (PE) the sternal depression may cause distortion of the cardiac chambers and great vessels. The aim of our study was to determine if the sternal impingement causes significant inferior vena cava (IVC) compression. Methods: Retrospective study of patients with severe PE assessed between 2015-2017. The antero-posterior (AP) and transverse diameters of the suprahepatic IVC were measured on a cardiac-MRI at the level of the diaphragmatic hiatus. Results were compared with patients that had a thoracic image study performed for other causes, adjusting for age and sex. Results: Among the 81 patients, 28 cases and 53 controls, 63% were males and had a mean age of 12.9±0.5 yrs. Significant differences were found between groups in both AP and transverse diameter of the IVC: 13.3±0.75 mm vs. 15.8±0.76 mm (p=0.001) and 28.8±1.34 mm vs. 27.1±0.89mm (p=0.045) respectively. After adjusting for age and sex, these differences were only statistically significant for AP IVC diameter in males 12.7±0.5 mm (95% CI 11.66-13.79 mm) vs. 16.6±0.5 mm (95% CI 15.69-17.56 mm) (p=0.000). The Pearson correlation coefficient for the Haller index was r=0.471 (p=0.01). Conclusion: Male patients with severe sternal depression show changes in the IVC diameter that may correspond to compression. These changes are correlated with the severity of the deformity and can justify certain clinical symptoms and cardiac function abnormalities in patients with severe PE

[Primary central nervous system lymphoma in a unusual site: a diagnostic challenge]. / Linfoma primario del sistema nervioso central de localizacion inhabitual: un reto diagnostico.

TITLE: Linfoma primario del sistema nervioso central de localizacion inhabitual: un reto diagnostico.

Levels of anti-Müllerian hormone in premenopausal women with the antiphospholipid syndrome and its association with the risk of clinical complications.

OBJECTIVE: The study aims to investigate the ovarian reserve in premenopausal women with antiphospholipid syndrome (APS) and to evaluate whether it is associated with cumulative organ damage or the risk of clinical complications. METHODS: This single-center study was conducted in 23 premenopausal female patients (10 with primary APS and 13 with secondary APS) and 24 healthy volunteers. Serum anti-Müllerian hormone (AMH) levels were measured by enzyme-linked immunoassay. Disease-specific organ damage (DIAPS score) and the risk of clinical complications (aGAPSS score) were additionally evaluated in APS patients. RESULTS: Serum AMH levels were similar in APS patients (median 6.06, interquartile range 4.31-7.54 ng/ml) and in controls (4.87, 2.64-6.40 ng/ml; P = 0.116), and no differences were observed between the primary (6.60, 5.49-8.88 ng/ml) and secondary (6.06, 3.91-7.30 ng/ml; P = 0.532) forms of the syndrome. In individuals with APS, serum AMH levels correlated inversely with the aGAPSS score (rho-0.421, 95% confidence intervals -0.716 to -0.001; P = 0.045), while no associations were observed with the DIAPS score (rho-0.001, -0.423 to 0.422; P = 0.996). CONCLUSIONS: Ovarian reserve is not reduced in premenopausal women with APS. In addition, serum AMH levels may reflect the risk of APS-related clinical complications but not the burden of disease-specific organ damage.

[Intranodal lymphangiography in pediatric chylothorax, a diagnostic and therapeutic tool]. / Linfangiografía intranodal en quilotórax pediátrico, una herramienta diagnóstica y terapéutica.

INTRODUCTION: High morbidity has been described in secondary chylothorax. Thoracic duct embolization (TDE) after intranodal lymphangiography (IL) is one of the treatments in adults but there is poor experience in children. We aim to describe our experience with this technique for refractory pediatric chylothorax. METHODS: A retrospective study of patients with refractory chylothorax treated with thoracic duct embolization at our Institution in the last 4 years was performed. Lymphatic vessels visualization was obtained by intranodal lymphangiography with ethiodized oil. Demographic and clinical data as well as imaging findings were collected. RESULTS: A total of 4 patients were treated during the study period with a median of age and weight of 2.5 months (1-16) and 4.25 kg (2.8-10) respectively. Chylothorax was secondary to cardiothoracic surgery in 3 patients and to venous thrombosis in the other one. Medical treatment was provided during a median of 47 days (13-56) without benefit in thoracic output [median: 46 ml/kg/day (19-64)]. After IL, thoracic duct catheterization was achieved in one patient however embolization was not possible. Chylothorax stopped in the 3 post-surgical patients regardless of how much lymphatic visualization was achieved in IL. In the venous thrombosis patient surgical treatment was performed 6 days after the study. CONCLUSION: IL can be a diagnostic and therapeutic tool in children. Ethiodized oil seems to seal lymphatic leak in postsurgical chylothorax. IL could be an option for chylothorax in patients too sick for surgical treatment or in whom thoracic duct embolization is not feasible.

INTRODUCCION: El quilotórax secundario es una entidad rara con una alta morbilidad. La embolización del conducto torácico (CT) mediante linfangiografía intranodal (LI) con aceite etiodizado (AE) forma parte del arsenal terapéutico del quilotórax en el adulto. Presentamos nuestra experiencia con esta técnica en pacientes pediátricos con quilotórax refractario al tratamiento médico. METODOS: Estudio retrospectivo de los pacientes tratados en nuestro centro por quilotórax refractario con LI en los últimos 4 años. Se recogieron los datos epidemiológicos, clínicos, terapéuticos y linfangiográficos. RESULTADOS: Se identificaron 4 pacientes, con unas medianas de edad y peso de 2,5 meses (1-16) y 4,25 kg (2,8-10) respectivamente. En 3 de los pacientes el quilotórax fue secundario a cirugía cardiaca y en el restante a trombosis extensa de vena cava superior. La mediana de débito fue de 46 ml/kg/día (19-64) y la de tiempo de tratamiento médico de 47 días (13-56). En todos ellos se realizó LI, opacificándose el CT solo en un paciente, sin lograrse la embolización. A pesar de ello, tras la LI, el quilotórax cesó en el grupo postquirúrgico independientemente del nivel de opacificación del árbol linfático. En el paciente secundario a trombosis, se realizó ligadura quirúrgica del CT 6 días después del estudio. CONCLUSIONES: La LI es una técnica diagnóstica e incluso terapéutica en casos de quilotórax refractario, que comienza a ser necesaria y realizable en centros con experiencia. El AE parece sellar la fuga linfática por un mecanismo embolizante en casos postquirúrgicos, eliminando la necesidad del cierre quirúrgico.

Linfangiografía intranodal en quilotórax pediátrico, una herramienta diagnóstica y terapéutica / Intranodal lymphangiography in pediatric chylothorax, a diagnostic and therapeutic tool

Introducción: El quilotórax secundario es una entidad rara con una alta morbilidad. La embolización del conducto torácico (CT) mediante linfangiografía intranodal (LI) con aceite etiodizado (AE) forma parte del arsenal terapéutico del quilotórax en el adulto. Presentamos nuestra experiencia con esta técnica en pacientes pediátricos con quilotórax refractario al tratamiento médico. Métodos: Estudio retrospectivo de los pacientes tratados en nuestro centro por quilotórax refractario con LI en los últimos 4 años. Se recogieron los datos epidemiológicos, clínicos, terapéuticos y linfangiográficos. Resultados: Se identificaron 4 pacientes, con unas medianas de edad y peso de 2,5 meses (1-16) y 4,25 kg (2,8-10) respectivamente. En 3 de los pacientes el quilotórax fue secundario a cirugía cardiaca y en el restante a trombosis extensa de vena cava superior. La mediana de débito fue de 46 ml/kg/día (19-64) y la de tiempo de tratamiento médico de 47 días (13-56). En todos ellos se realizó LI, opacificándose el CT solo en un paciente, sin lograrse la embolización. A pesar de ello, tras la LI, el quilotórax cesó en el grupo postquirúrgico independientemente del nivel de opacificación del árbol linfático. En el paciente secundario a trombosis, se realizó ligadura quirúrgica del CT 6 días después del estudio. Conclusiones: La LI es una técnica diagnóstica e incluso terapéutica en casos de quilotórax refractario, que comienza a ser necesaria y realizable en centros con experiencia. El AE parece sellar la fuga linfática por un mecanismo embolizante en casos postquirúrgicos, eliminando la necesidad del cierre quirúrgico

Introduction: High morbidity has been described in secondary chylothorax. Thoracic duct embolization (TDE) after intranodal lymphangiography (IL) is one of the treatments in adults but there is poor experience in children. We aim to describe our experience with this technique for refractory pediatric chylothorax. Methods: A retrospective study of patients with refractory chylothorax treated with thoracic duct embolization at our Institution in the last 4 years was performed. Lymphatic vessels visualization was obtained by intranodal lymphangiography with ethiodized oil. Demographic and clinical data as well as imaging findings were collected. Results: A total of 4 patients were treated during the study period with a median of age and weight of 2.5 months (1-16) and 4.25 kg (2.810) respectively. Chylothorax was secondary to cardiothoracic surgery in 3 patients and to venous thrombosis in the other one. Medical treatment was provided during a median of 47 days (13-56) without benefit in thoracic output [median: 46 ml/kg/day (19-64)]. After IL, thoracic duct catheterization was achieved in one patient however embolization was not possible. Chylothorax stopped in the 3 post-surgical patients regardless of how much lymphatic visualization was achieved in IL. In the venous thrombosis patient surgical treatment was performed 6 days after the study. Conclusion: IL can be a diagnostic and therapeutic tool in children. Ethiodized oil seems to seal lymphatic leak in postsurgical chylothorax. IL could be an option for chylothorax in patients too sick for surgical treatment or in whom thoracic duct embolization is not feasible