Role of the first WHO mutation catalogue in the diagnosis of antibiotic resistance in Mycobacterium tuberculosis in the Valencia Region, Spain: a retrospective genomic analysis.

BACKGROUND: In June, 2021, WHO published the most complete catalogue to date of resistance-conferring mutations in Mycobacterium tuberculosis. Here, we aimed to assess the performance of genome-based antimicrobial resistance prediction using the catalogue and its potential for improving diagnostics in a real low-burden setting. METHODS: In this retrospective population-based genomic study M tuberculosis isolates were collected from 25 clinical laboratories in the low-burden setting of the Valencia Region, Spain. Culture-positive tuberculosis cases reported by regional public health authorities between Jan 1, 2014, and Dec 31, 2016, were included. The drug resistance profiles of these isolates were predicted by the genomic identification, via whole-genome sequencing (WGS), of the high-confidence resistance-causing variants included in the catalogue and compared with the phenotype. We determined the minimum inhibitory concentration (MIC) of the isolates with discordant resistance profiles using the resazurin microtitre assay. FINDINGS: WGS was performed on 785 M tuberculosis complex culture-positive isolates, and the WGS resistance prediction sensitivities were: 85·4% (95% CI 70·8-94·4) for isoniazid, 73·3% (44·9-92·2) for rifampicin, 50·0% (21·1-78·9) for ethambutol, and 57·1% (34·0-78·2) for pyrazinamide; all specificities were more than 99·6%. Sensitivity values were lower than previously reported, but the overall pan-susceptibility accuracy was 96·4%. Genotypic analysis revealed that four phenotypically susceptible isolates carried mutations (rpoB Leu430Pro and rpoB Ile491Phe for rifampicin and fabG1 Leu203Leu for isoniazid) known to give borderline resistance in standard phenotypic tests. Additionally, we identified three putative resistance-associated mutations (inhA Ser94Ala, katG Leu48Pro, and katG Gly273Arg for isoniazid) in samples with substantially higher MICs than those of susceptible isolates. Combining both genomic and phenotypic data, in accordance with the WHO diagnostic guidelines, we could detect two new multidrug-resistant cases. Additionally, we detected 11 (1·6%) of 706 isolates to be monoresistant to fluoroquinolone, which had been previously undetected. INTERPRETATION: We showed that the WHO catalogue enables the detection of resistant cases missed in phenotypic testing in a low-burden region, thus allowing for better patient-tailored treatment. We also identified mutations not included in the catalogue, relevant at the local level. Evidence from this study, together with future updates of the catalogue, will probably lead in the future to the partial replacement of culture testing with WGS-based drug susceptibility testing in our setting. FUNDING: European Research Council and the Spanish Ministerio de Ciencia.

Population-based sequencing of Mycobacterium tuberculosis reveals how current population dynamics are shaped by past epidemics.

Transmission is a driver of tuberculosis (TB) epidemics in high-burden regions, with assumed negligible impact in low-burden areas. However, we still lack a full characterization of transmission dynamics in settings with similar and different burdens. Genomic epidemiology can greatly help to quantify transmission, but the lack of whole genome sequencing population-based studies has hampered its application. Here, we generate a population-based dataset from Valencia region and compare it with available datasets from different TB-burden settings to reveal transmission dynamics heterogeneity and its public health implications. We sequenced the whole genome of 785 Mycobacterium tuberculosis strains and linked genomes to patient epidemiological data. We use a pairwise distance clustering approach and phylodynamic methods to characterize transmission events over the last 150 years, in different TB-burden regions. Our results underscore significant differences in transmission between low-burden TB settings, i.e., clustering in Valencia region is higher (47.4%) than in Oxfordshire (27%), and similar to a high-burden area as Malawi (49.8%). By modeling times of the transmission links, we observed that settings with high transmission rate are associated with decades of uninterrupted transmission, irrespective of burden. Together, our results reveal that burden and transmission are not necessarily linked due to the role of past epidemics in the ongoing TB incidence, and highlight the need for in-depth characterization of transmission dynamics and specifically tailored TB control strategies.

Field performance of the Abbott RealTime MTB assay for the diagnosis of extrapulmonary tuberculosis in a low-prevalence setting / Neumonía en niños: el papel de las pruebas de diagnóstico rápido de virus en la administración de antimicrobianos

INTRODUCTION: The sensitivities of conventional mycobacterial culture in solid or liquid media and acid-fast bacilli (AFB) smear microscopy for Mycobacterium tuberculosis complex (MTBC) detection in extrapulmonary specimens are suboptimal. We evaluated the field performance of the Abbott RealTime MTB assay for the diagnosis of extrapulmonary tuberculosis in a low-prevalence setting. METHODS: The total number of extrapulmonary specimens with mycobacterial culture and PCR results was 566: sterile fluids (n = 278), non-sterile fluids (n = 147), lymph node material (n = 69) tissue biopsies (n = 63), and abscess aspirates (n = 9). A composite standard consisting of mycobacterial culture results, clinical treatment response to anti-TB drugs, when administered, and histopathology, radiological and laboratory findings were used as a reference for sensitivity and specificity calculations. RESULTS: Mycobacterial cultures and PCR were positive in 17 and 28 specimens, respectively. The overall agreement between culture and PCR was moderate (Cohen's kappa coefficient: 0.549; P = 0.0001). Taking as a reference our composite standard, the sensitivity of the Abbott PCR assay was 77.7%, the specificity 99.5%, the PPV 95.4%, and the NPV 98.8%. In turn, the sensitivity of the mycobacterial culture was 62.9%, the specificity and PPV 100%, and the NPV 97.9%. CONCLUSIÓN: The good field performance of the Abbott RealTime MTB assay makes it valuable for the diagnosis of extrapulmonary tuberculosis in a low-prevalence setting. The use of molecular methods along with culture improves the diagnosis of extrapulmonary tuberculosis

INTRODUCCIÓN: La sensibilidad del cultivo convencional de micobacterias en medios sólidos o líquidos y la de la microscopía de bacilos ácido-alcohol resistentes para detectar el complejo Mycobacterium tuberculosis en muestras extrapulmonares es subóptima. Evaluamos el rendimiento del ensayo Abbott RealTime MTB para el diagnóstico de la tuberculosis extrapulmonar en un entorno de baja prevalencia. MÉTODOS: El número total de muestras extrapulmonares con cultivo de micobacterias y resultados de la reacción en cadena de la polimerasa fue de 566: líquidos estériles (n = 278), líquidos no estériles (n = 147), material de los ganglios linfáticos (n = 69), biopsias de tejido (n = 63) y aspiraciones de abscesos (n = 9). Para calcular la sensibilidad y la especificidad del ensayo se utilizó como referencia un parámetro que incluyó: resultados del cultivo, respuesta clínica al tratamiento con antituberculosos y hallazgos de laboratorio, radiológicos e histopatológicos. RESULTADOS: Los cultivos de micobacterias y la PCR fueron positivos en 17 y 28 muestras, respectivamente. La concordancia de los resultados obtenidos por ambos métodos fue moderada (coeficiente kappa de Cohen: 0,549; p = 0,0001). La sensibilidad de la PCR de Abbott fue del 77,7%, especificidad del 99,5 %, valor predictivo positivo del 95,4% y valor predictivo negativo del 98,8%. La sensibilidad del cultivo fue del 62,9%, la especificidad y el valor predictivo positivo del 100% y el valor predictivo negativo del 97,9%. CONCLUSIÓN: El buen rendimiento del ensayo Abbott RealTime MTB lo hace valioso para el diagnóstico de la tuberculosis extrapulmonar en un entorno de baja prevalencia. El uso de métodos moleculares junto al cultivo mejora el diagnóstico de la tuberculosis extrapulmonar

Field performance of the Abbott RealTime MTB assay for the diagnosis of extrapulmonary tuberculosis in a low-prevalence setting.

INTRODUCTION: The sensitivities of conventional mycobacterial culture in solid or liquid media and acid-fast bacilli (AFB) smear microscopy for Mycobacterium tuberculosis complex (MTBC) detection in extrapulmonary specimens are suboptimal. We evaluated the field performance of the Abbott RealTime MTB assay for the diagnosis of extrapulmonary tuberculosis in a low-prevalence setting. METHODS: The total number of extrapulmonary specimens with mycobacterial culture and PCR results was 566: sterile fluids (n=278), non-sterile fluids (n=147), lymph node material (n=69) tissue biopsies (n=63), and abscess aspirates (n=9). A composite standard consisting of mycobacterial culture results, clinical treatment response to anti-TB drugs, when administered, and histopathology, radiological and laboratory findings were used as a reference for sensitivity and specificity calculations. RESULTS: Mycobacterial cultures and PCR were positive in 17 and 28 specimens, respectively. The overall agreement between culture and PCR was moderate (Cohen's kappa coefficient: 0.549; P=0.0001). Taking as a reference our composite standard, the sensitivity of the Abbott PCR assay was 77.7%, the specificity 99.5%, the PPV 95.4%, and the NPV 98.8%. In turn, the sensitivity of the mycobacterial culture was 62.9%, the specificity and PPV 100%, and the NPV 97.9%. CONCLUSION: The good field performance of the Abbott RealTime MTB assay makes it valuable for the diagnosis of extrapulmonary tuberculosis in a low-prevalence setting. The use of molecular methods along with culture improves the diagnosis of extrapulmonary tuberculosis.

High-resolution mapping of tuberculosis transmission: Whole genome sequencing and phylogenetic modelling of a cohort from Valencia Region, Spain.

BACKGROUND: Whole genome sequencing provides better delineation of transmission clusters in Mycobacterium tuberculosis than traditional methods. However, its ability to reveal individual transmission links within clusters is limited. Here, we used a 2-step approach based on Bayesian transmission reconstruction to (1) identify likely index and missing cases, (2) determine risk factors associated with transmitters, and (3) estimate when transmission happened. METHODS AND FINDINGS: We developed our transmission reconstruction method using genomic and epidemiological data from a population-based study from Valencia Region, Spain. Tuberculosis (TB) incidence during the study period was 8.4 cases per 100,000 people. While the study is ongoing, the sampling frame for this work includes notified TB cases between 1 January 2014 and 31 December 2016. We identified a total of 21 transmission clusters that fulfilled the criteria for analysis. These contained a total of 117 individuals diagnosed with active TB (109 with epidemiological data). Demographic characteristics of the study population were as follows: 80/109 (73%) individuals were Spanish-born, 76/109 (70%) individuals were men, and the mean age was 42.51 years (SD 18.46). We found that 66/109 (61%) TB patients were sputum positive at diagnosis, and 10/109 (9%) were HIV positive. We used the data to reveal individual transmission links, and to identify index cases, missing cases, likely transmitters, and associated transmission risk factors. Our Bayesian inference approach suggests that at least 60% of index cases are likely misidentified by local public health. Our data also suggest that factors associated with likely transmitters are different to those of simply being in a transmission cluster, highlighting the importance of differentiating between these 2 phenomena. Our data suggest that type 2 diabetes mellitus is a risk factor associated with being a transmitter (odds ratio 0.19 [95% CI 0.02-1.10], p < 0.003). Finally, we used the most likely timing for transmission events to study when TB transmission occurred; we identified that 5/14 (35.7%) cases likely transmitted TB well before symptom onset, and these were largely sputum negative at diagnosis. Limited within-cluster diversity does not allow us to extrapolate our findings to the whole TB population in Valencia Region. CONCLUSIONS: In this study, we found that index cases are often misidentified, with downstream consequences for epidemiological investigations because likely transmitters can be missed. Our findings regarding inferred transmission timing suggest that TB transmission can occur before patient symptom onset, suggesting also that TB transmits during sub-clinical disease. This result has direct implications for diagnosing TB and reducing transmission. Overall, we show that a transition to individual-based genomic epidemiology will likely close some of the knowledge gaps in TB transmission and may redirect efforts towards cost-effective contact investigations for improved TB control.

Missing Cases of Herpes Simplex Virus (HSV) Infection of the Central Nervous System When the Reller Criteria Are Applied for HSV PCR Testing: a Multicenter Study.

Previous studies suggested that herpes simplex virus (HSV) PCR testing can be safely deferred in patients with normal cerebrospinal fluid (CSF) white blood cell (WBC) counts and protein levels as long as they are older than 2 years of age and are not immunocompromised, the so-called Reller criteria. In this multicenter study, we retrospectively assessed the validity of these screening criteria in our setting. A total of 4,404 CSF specimens submitted for HSV PCR testing to the respective microbiology laboratories at the participating hospitals between 2012 and 2018 were included. Six commercially available HSV PCR assays were used across the participating centers. Ninety-one of the 4,404 CSF specimens (2.1%) tested were positive for HSV DNA (75 samples for HSV-1 and 16 for HSV-2). Nine patients failed to meet the Reller criteria, of whom seven were deemed to truly have HSV encephalitis. Overall, no significant correlation between HSV PCR cycle threshold (CT ) values and WBC counts or total protein levels was found. In addition, median HSV PCR CT s were comparable between patients who met the Reller criteria and those who did not (P = 0.531). In summary, we show that HSV DNA may be detected in CSF specimens with normal WBC and protein levels collected from immunocompetent individuals older than 2 years with HSV encephalitis. Nevertheless, the data also indicate that the number of cases detected could be lowered at least by half if CSF specimens with borderline WBC counts (4 cells/mm3) as well as children of any age are systematically tested.

A survey on practices for active surveillance of carriage of multidrug-resistant bacteria in hospitals in the Autonomous Community of Valencia, Spain.

A questionnaire-based cross-sectional study was conducted to gather information on current microbiological practices for active surveillance of carriage of multidrug-resistant (MDR) bacteria in hospitals from 14 health departments of the Autonomous Community of Valencia (ACV), Spain, which together provided medical attention to 3,271,077 inhabitants in 2017, approximately 70% of the population of the ACV. The survey consisted of 35 questions on MDR bacteria screening policies, surveillance approach chosen (universal vs. targeted), and microbiological methods and processes in use for routine detection and reporting of colonization by MDR bacteria, including the anatomical sites scheduled to be sampled for each MDR bacterial species, and the methodology employed (culture-based, molecular-based, or both). Our study revealed striking differences across centers, likely attributable to the lack of consensus on optimal protocols for sampling, body sites for screening, and microbiological testing, thus underscoring the need for consensus guidelines on these issues.

First demonstration and field trial on multi-user UDWDM-PON full duplex PSK-PSK with single monolithic integrated dual-output-DFB-SOA based ONUs.

We demonstrate a monolithically integrated dual-output DFB-SOA, and conduct the field trial on a multi-user bidirectional coherent ultradense wavelength division multiplexing-passive optical network (UDWDM-PON). To the best of our knowledge, this is the first achievement of simplified single integrated laser-based neighboring coherent optical network units (ONUs) with a 12.5 GHz channel spaced ultra-dense access network, including both downstream and upstream, taking the benefits of low footprint and low-temperature dependence.

Adhesion of dental porcelain to cast, milled, and laser-sintered cobalt-chromium alloys: shear bond strength and sensitivity to thermocycling.

STATEMENT OF PROBLEM: New technologies have led to the introduction of new materials, so an evaluation of the adhesion of ceramics to these materials is needed. PURPOSE: The purpose of this study was to compare the shear bond strength of dental porcelain to cast, milled, and laser-sintered cobalt-chromium alloys, and to investigate the adhesive bond and failure type after thermocycling, 90 metal cylinders (10 mm diameter and 10 mm height) were prepared from cast (30 specimens), milled (30 specimens), and laser-sintered (30 specimens) alloys. MATERIAL AND METHODS: Ceramic cylinders (2.5 mm diameter and 4 mm length) were fused to the alloy cylinders. For each group, 15 specimens were thermocycled 5500 times at temperatures between 4°C and 60°C before testing. After testing, the specimen surfaces were visually examined to determine the failure mode. Differences in adhesion values according to manufacturing method, testing condition (thermocycling or no thermocycling), and interaction between the factors were evaluated with a 2-way ANOVA. The χ(2) test (95% confidence level) was performed to determine whether the failure mode was associated with the testing condition. RESULTS: Adhesion strengths for the nonthermocycled specimens were 42.79 ±14.14 MPa (cast), 37.56 ±9.18 MPa (milled), and 29.09 ±6.95 MPa (laser-sintered), and, for the thermocycled specimens, 16.52 ±8.96 MPa (cast), 22.21 ±13.25 MPa (milled), and 24.28 ±10.13 MPa (laser-sintered). Two-way ANOVA results indicated no statistically significant differences in adhesion among the manufacturing methods (P=.257), but statistically significant differences were observed according to both testing conditions (P<.001) and interaction between the factors (P=.015). The χ(2) test indicated that the failure mode was not associated with the testing condition (thermocycled, P=.280; nonthermocycled, P=.240). CONCLUSIONS: The porcelain adhesion values for all the materials were adequate for clinical applications. No significant adhesion differences were observed between cast, milled, and laser-sintered specimens, or among thermocycled and nonthermocycled laser-sintered specimens. However, significant adhesion differences were observed among the thermocycled and nonthermocycled cast and the milled specimens.

Simple intradyne PSK system for udWDM-PON.

A homodyne coherent receiver for ultra-dense WDM-PON with off the shelf components is presented. It consists of a conventional DFB, phase switched clock signal, an optical coupler instead of a 90° hybrid, balanced photodetectors and digital signal processing. The phase swing for a DBPSK signal was optimized and the performance was experimentally evaluated in terms of the sensitivity for several laser linewidths. The acceptable frequency offset and clock time delay was also assessed. The results exhibit a sensitivity of -48 dBm at a BER of 10(-3) and indicate a high tolerance to phase noise.

Enfermedad pulmonar obstructiva crónica en el anciano: próximo fenotipo / Chronic obstructive pulmonary disease in the elderly: next phenotype

No disponible

Identification of recent HIV-1 infection among newly diagnosed cases in Catalonia, Spain (2006-08).

BACKGROUND: Quantification and description of patients recently infected by HIV can provide an accurate estimate of the dynamics of HIV transmission. Between 2006 and 2008 in Catalonia, we estimated the prevalence of recent HIV infection among newly diagnosed cases, described the epidemiological characteristics of the infection according to whether it was recent, long-standing or advanced, and identified factors associated with recent infection. METHODS: A Test for Recent Infection (TRI) was performed in serum samples from patients newly diagnosed with HIV. Two different TRI were used: the Vironostika-LS assay (January 2006-May 2007) and the BED-CEIA CEIA (June 2007 onwards). Samples were obtained within the first 6 months of diagnosis. Patients whose samples tested positive in the TRI were considered recently infected. RESULTS: Of 1125 newly diagnosed patients, 79.9% were men (median age, 35.4 years), 38.7% were born outside Spain, 48.9% were men who have sex with men (MSM) and 10.6% presented other sexually transmitted infections. The overall percentage of recent infection was 23.0%, which increased significantly, from 18.1% in 2006 to 26.2% in 2008. This percentage was higher for patients from South America (27.6%). Factors associated with recent infection were acquiring infection through sexual contact between MSM [odds ratio (OR) 2.0; 95% confidence interval (95% CI) 1.1-3.9], compared with acquiring infection through heterosexual relations and being under 30 years of age (OR 5.9; 95% CI 1.9-17.4), compared with being over 50 years of age. CONCLUSION: The highest percentage of recent infection was identified in MSM, suggesting either a higher incidence or a greater frequency of HIV testing. Information regarding testing patterns is necessary to correctly interpret data from recently infected individuals. Systems to monitor the HIV epidemic should include both parameters.

Prevalence of Transmitted Antiretroviral Resistance and Distribution of HIV-1Subtypes Among Patients with Recent Infection in Catalonia (Spain) between2003 and 2005

Los objetivos de este estudio fueron evaluar la prevalencia de las resistencias primarias transmitidas (RPT)y de subtipos de VIH-1 en pacientes recientemente infectados en Cataluña entre 2003 y 2005, y describirlas características de estos pacientes según la presencia o ausencia de RPT y el subtipo de VIH-1.Métodos: Después de la aplicación del algoritmo de pruebas serológicas para la seroconversión reciente al VIH (STARHS), alícuotas residuales de las muestras de suero de individuos recientemente infectados no tratados previamente con antirretrovirales fueron genotipados. Las secuencias FASTA se analizaron conel programa HIV db. Se utilizó el listado de mutaciones de la Organización Mundial de la Salud del 2009para estimar la prevalencia de resistencias transmitidas. Resultados: De 182 pacientes recientemente infectados, 14 (7,7%) presentaron RPT. Siete personas (3,8%)presentaban evidencias genotípica de RPT a los inhibidores de la transcriptasa inversa no análogos anucleósidos, 6 (3,3%) frente a inhibidores de la transcriptasa inversa análogos de nucleósidos, 3 (1,6%)frente a los inhibidores de la proteasa, y solo 2 personas (1,1%) presentaron RPT a más de una familia de medicamentos. Treinta y cinco (19,2%) pacientes estaban infectados con un subtipo no-B del VIH-1.Conclusión: Este es el primer estudio que estima la prevalencia de RPT en pacientes recientemente infectadosen Cataluña, y los resultados son similares a los de estudios realizados en otras regiones españolas. Para el adecuado seguimiento de estos parámetros es necesaria la vigilancia epidemiológica sistemática de las RPT (AU)

Objectives: The objectives of this study were to assess the prevalence of transmitted HIV-1 drug resistances(TDR) and HIV-1 subtypes in recently infected patients in Catalonia between 2003 and 2005 and to describe the characteristics of these patients according to the presence or absence of TDR and HIV-1subtype.Methods: After application of the Serological Testing Algorithm for Recent HIV Seroconversion (STARHS),residual aliquots of serum samples from recently infected antiretroviral-naïve individuals were genotyped. FASTA sequences were analyzed using the HIVDB Program. The World Health Organization 2009List of Mutations for Surveillance of Transmitted HIV-1 Drug Resistant HIV Strains was used to estimate the prevalence of TDR. Results: Of 182 recently infected patients, 14 (7.7%) presented TDR. Seven (3.8%) had genotypic evidence of TDR against non-nucleoside reverse transcriptase inhibitors, 6 (3.3%) against nucleoside reverse transcriptase inhibitors, 3 (1.6%) against protease inhibitors (PIs), and only 2 individuals (1.1%) presented TDR against more than one class of drugs. Thirty-five (19.2%) patients were infected with a non-B HIV-1subtype.Conclusion: This is the first study to estimate the prevalence of TDR in recently infected patients in Catalonia. The results are similar to those of studies performed in other Spanish regions. Correct monitoring of these parameters requires systematic epidemiologic surveillance of transmitted resistance (AU)

Prevalence of transmitted antiretroviral resistance and distribution of HIV-1 subtypes among patients with recent infection in Catalonia (Spain) between 2003 and 2005.

OBJECTIVES: The objectives of this study were to assess the prevalence of transmitted HIV-1 drug resistances (TDR) and HIV-1 subtypes in recently infected patients in Catalonia between 2003 and 2005 and to describe the characteristics of these patients according to the presence or absence of TDR and HIV-1 subtype. METHODS: After application of the Serological Testing Algorithm for Recent HIV Seroconversion (STARHS), residual aliquots of serum samples from recently infected antiretroviral-naïve individuals were genotyped. FASTA sequences were analyzed using the HIVDB Program. The World Health Organization 2009 List of Mutations for Surveillance of Transmitted HIV-1 Drug Resistant HIV Strains was used to estimate the prevalence of TDR. RESULTS: Of 182 recently infected patients, 14 (7.7%) presented TDR. Seven (3.8%) had genotypic evidence of TDR against non-nucleoside reverse transcriptase inhibitors, 6 (3.3%) against nucleoside reverse transcriptase inhibitors, 3 (1.6%) against protease inhibitors (PIs), and only 2 individuals (1.1%) presented TDR against more than one class of drugs. Thirty-five (19.2%) patients were infected with a non-B HIV-1 subtype. CONCLUSION: This is the first study to estimate the prevalence of TDR in recently infected patients in Catalonia. The results are similar to those of studies performed in other Spanish regions. Correct monitoring of these parameters requires systematic epidemiologic surveillance of transmitted resistance.

Combinación de fibrosis pulmonar y enfisema / Combined Pulmonary Fibrosis and Emphysema

La combinación de fibrosis pulmonar y enfisema (CFPE), es un síndrome definido recientemente, en el cual coexisten en un mismo individuo enfisema en lóbulos superiores y fibrosis en lóbulos inferiores. Estos pacientes presentan un perfil funcional respiratorio característico, con volúmenes pulmonares dinámicos y estáticos aparentemente normales o mínimamente alterados que contrastan con una grave alteración de la difusión del monóxido de carbono (DLCO) e hipoxemia arterial, la cual empeora durante el esfuerzo. La prevalencia de hipertensión pulmonar es elevada y representa la principal condición que determina el pronóstico. La Tomografía axial computarizada de alta resolución (TCAR) constituye la herramienta primordial para confirmar su diagnóstico. Se ha postulado al humo del tabaco como el principal agente etiológico, sin embargo, ni los mecanismos fisiopatológicos ni la secuencia de eventos involucrados en este síndrome ha sido aún dilucidados. Estudios experimentales en modelos animales, están proporcionando información sobre la participación de algunos mediadores inflamatorios en su patogenia. Actualmente, no existe un consenso sobre la actitud terapéutica a seguir en estos pacientes, puesto que lo publicado hasta la fecha sobre esta entidad se limita a series de casos bien caracterizadas. Es por tanto, una patología con múltiples incógnitas todavía por resolver y con alta probabilidad de ser infradiagnosticada si no se tienen en cuenta sus particularidades clínico-funcionales(AU)

The combination of pulmonary fibrosis and emphysema (CPFE) is a recently defined syndrome, in which anupper lobe emphysema and lower lobe fibrosis coexist in a single patient. These patients have a characteristic lung function profile, with dynamic and static lung volumes apparently normal or minimally altered, contrasting with a significant reduction of carbon monoxide transfer (DLco) and exercise hypoxemia. Pulmonary hypertension is highly prevalent and is the principal negative prognostic factor for this condition. High resolution computed axial tomography (HRCT) is the main tool to confirm the diagnosis. Cigarette smoking has been proposed as the main factor in its etiology; however, neither pathogenic mechanisms nor the sequence of events involved in this syndrome has been clarified yet. Experimental studies in animal models are providing information on the involvement of some inflammatory mediators in the pathogenesis. There is currently no consensus on the therapeutic approach to be followed in these patients, since those published to date on this subject are limited to well-characterised series of cases. Therefore, it is a pathology with many unknowns yet to be resolved and highly likely to be underdiagnosed, unless its functional clinical characteristics are taken into acount(AU)

[Combined pulmonary fibrosis and emphysema]. / Combinación de fibrosis pulmonar y enfisema.

The combination of pulmonary fibrosis and emphysema (CPFE) is a recently defined syndrome, in which an upper lobe emphysema and lower lobe fibrosis coexist in a single patient. These patients have a characteristic lung function profile, with dynamic and static lung volumes apparently normal or minimally altered, contrasting with a significant reduction of carbon monoxide transfer (DLco) and exercise hypoxemia. Pulmonary hypertension is highly prevalent and is the principal negative prognostic factor for this condition. High resolution computed axial tomography (HRCT) is the main tool to confirm the diagnosis. Cigarette smoking has been proposed as the main factor in its etiology; however, neither pathogenic mechanisms nor the sequence of events involved in this syndrome has been clarified yet. Experimental studies in animal models are providing information on the involvement of some inflammatory mediators in the pathogenesis. There is currently no consensus on the therapeutic approach to be followed in these patients, since those published to date on this subject are limited to well-characterised series of cases. Therefore, it is a pathology with many unknowns yet to be resolved and highly likely to be underdiagnosed, unless its functional clinical characteristics are taken into account.

Tratamiento del paciente con ronquidos simples / Treatment of Patients With Simple Snoring

En los pacientes afectados de síndrome de apneas obstructivas durante el sueño, el tratamiento del ronquido forma parte de las medidas terapéuticas que se han de aplicar para tratar el síndrome. Sin embargo, en los sujetos que roncan y no presentan dicho síndrome el tratamiento del ronquido debería ir en relación con su intensidad. Se recomienda iniciar las medidas terapéuticas generales y específicas en los pacientes roncadores cuyo sueño no sea reparador, impida el descanso de la pareja o bien se acompañe de otras enfermedades cardiovasculares. En la presente revisión se hace una relación de las diferentes opciones terapéuticas y del estado actual del conocimiento de cada una de ellas, incidiendo en sus posibles indicaciones y en el control de la eficacia de las mismas(AU)

Management of snoring is part of the treatment offered to patients with obstructive sleep apnea syndrome. In patients who do not have this syndrome, however, snoring should be treated according to the severity of the condition. General or specific therapeutic measures should be applied to snorers that have concomitant cardiovascular disease or unrefreshing sleep and in cases in which an individual's snoring disturbs his/her partner's sleep. The present review examines the treatments currently available for snorers and the current state of knowledge regarding each option. It will also focus on the possible indications of these treatments and evaluate their effectiveness(AU)

[Treatment of patients with simple snoring]. / Tratamiento del paciente con ronquidos simples.

Management of snoring is part of the treatment offered to patients with obstructive sleep apnea syndrome. In patients who do not have this syndrome, however, snoring should be treated according to the severity of the condition. General or specific therapeutic measures should be applied to snorers that have concomitant cardiovascular disease or unrefreshing sleep and in cases in which an individual's snoring disturbs his/her partner's sleep. The present review examines the treatments currently available for snorers and the current state of knowledge regarding each option. It will also focus on the possible indications of these treatments and evaluate their effectiveness.