Reevaluación de los efectos de PEEP alta con maniobras de reclutamiento vs. PEEP baja sin maniobras de reclutamiento durante la anestesia general para cirugía: protocolo y plan de análisis estadístico para un metaanálisis de los datos de pacientes individuales de PROVHILO, iPROVE y PROBESE / Re-evaluation of the effects of high PEEP with recruitment manoeuvres versus low PEEP without recruitment manoeuvres during general anaesthesia for surgery -Protocol and statistical analysis plan for an individual patient data meta-analysis of PROVHILO, iPROVE and PROBESE

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Individualized lung recruitment maneuver guided by pulse-oximetry in anesthetized patients undergoing laparoscopy: a feasibility study.

BACKGROUND: We conducted this study to test whether pulse-oximetry hemoglobin saturation (SpO2 ) can personalize the implementation of an open-lung approach during laparoscopy. Thirty patients with SpO2  ≥ 97% on room-air before anesthesia were studied. After anesthesia and capnoperitoneum the FIO2 was reduced to 0.21. Those patients whose SpO2 decreased below 97% - an indication of shunt related to atelectasis - completed the following phases: (1) First recruitment maneuver (RM), until reaching lung's opening pressure, defined as the inspiratory pressure level yielding a SpO2 ≥ 97%; (2) decremental positive end-expiratory (PEEP) titration trial until reaching lung's closing pressure defined as the PEEP level yielding a SpO2  < 97%; (3) second RM and, (4) ongoing ventilation with PEEP adjusted above the detected closing pressure. RESULTS: When breathing air, in 24 of 30 patients SpO2 was < 97%, PaO2 /FIO2  Ë‚ 53.3 kPa and negative end-expiratory transpulmonary pressure (PTP-EE ). The mean (SD) opening pressures were found at 40 (5) and 33 (4) cmH2 O during the first and second RM, respectively (P < 0.001; 95% CI: 3.2-7.7). The closing pressure was found at 11 (5) cmH2 O. This SpO2 -guided approach increased PTP-EE (from -6.4 to 1.2 cmH2 O, P < 0.001) and PaO2 /FIO2 (from 30.3 to 58.1 kPa, P < 0.001) while decreased driving pressure (from 18 to 10 cmH2 O, P < 0.001). SpO2 discriminated the lung's opening and closing pressures with accuracy taking the reference parameter PTP-EE (area under the receiver-operating-curve of 0.89, 95% CI: 0.80-0.99). CONCLUSION: The non-invasive SpO2 monitoring can help to individualize an open-lung approach, including all involved steps, from the identification of those patients who can benefit from recruitment, the identification of opening and closing pressures to the subsequent monitoring of an open-lung condition.

A reference genome for Nicotiana tabacum enables map-based cloning of homeologous loci implicated in nitrogen utilization efficiency.

BACKGROUND: Tobacco (Nicotiana tabacum) is an important plant model system that has played a key role in the early development of molecular plant biology. The tobacco genome is large and its characterisation challenging because it is an allotetraploid, likely arising from hybridisation between diploid N. sylvestris and N. tomentosiformis ancestors. A draft assembly was recently published for N. tabacum, but because of the aforementioned genome complexities it was of limited utility due to a high level of fragmentation. RESULTS: Here we report an improved tobacco genome assembly, which, aided by the application of optical mapping, achieves an N50 size of 2.17 Mb and enables anchoring of 64% of the genome to pseudomolecules; a significant increase from the previous value of 19%. We use this assembly to identify two homeologous genes that explain the differentiation of the burley tobacco market class, with potential for greater understanding of Nitrogen Utilization Efficiency and Nitrogen Use Efficiency in plants; an important trait for future sustainability of agricultural production. CONCLUSIONS: Development of an improved genome assembly for N. tabacum enables what we believe to be the first successful map-based gene discovery for the species, and demonstrates the value of an improved assembly for future research in this model and commercially-important species.

Decreased levels of serum complement C3 and natural killer cells add to the predictive value of total immunoglobulin G for severe infection in heart transplant recipients.

BACKGROUND: Infection remains a source of mortality in heart recipients. We previously reported that post-transplant immunoglobulin G (IgG) quantification can help identify the risk for infection. We assessed whether other standardized parameters of humoral and cellular immunity could prove useful when identifying patients at risk of infection. METHODS: We prospectively studied 133 heart recipients over a 12-month period. Forty-eight patients had at least one episode of severe infection. An event was defined as an infection requiring intravenous antimicrobial therapy. RESULTS: Cox regression analysis revealed an association between the risk of developing infection and the following: lower IgG2 subclass levels (day 7: relative hazard [RH] 1.71; day 30: RH 1.76), lower IgA levels (day 7: RH 1.61; day 30: RH 1.91), lower complement C3 values (day 7: RH 1.25), lower CD3 absolute counts (day 30: RH 1.10), lower absolute natural killer [NK] cell count (day 7: RH 1.24), and lower IgG concentrations (day 7: RH 1.31; day 30: RH 1.36). Cox regression bivariate analysis revealed that lower day 7 C3 levels, IgG2 concentration, and absolute NK cell count remained significant after adjustment for total IgG levels. CONCLUSIONS: Data suggest that early immune monitoring including C3, IgG2, and NK cell testing in addition to IgG concentrations is useful when attempting to identify the risk of infection in heart transplant recipients.

Restoration of humoral immunity after intravenous immunoglobulin replacement therapy in heart recipients with post-transplant antibody deficiency and severe infections.

IgG hypogammaglobulinemia is a risk factor for infection in heart recipients. We assessed reconstitution of humoral immunity after non-specific intravenous immunoglobulin (IVIg) replacement therapy administered to treat secondary IgG hypogammaglobulinemia in heart recipients with severe infections. The study population comprised 55 heart recipients who were administered IVIg (IVIg group) and 55 heart recipients with no severe infectious complications (control group). An event was defined as a severe infection requiring intravenous drug therapy during the first year after transplantation. The IVIg protocol comprised non-specific 5% pasteurized IVIg at a dose of 300-400 mg/kg/months. IgG titers were lower in the IVIg group than in controls at seven d (577 vs. 778 mg/dL, p < 0.001) and at one month (553 vs. 684, p = 0.003). After IVIg therapy, IgG concentrations were similar in both groups at three months (681 vs. 737, p = 0.25) and at six months (736 vs. 769, p = 0.46). At three months, the IVIg group had higher levels of antitetanus toxoid and anti-HBs (ELISA, 2.07 ± 2.11 vs. 0.60 ± 1.24 mg/dL [p = 0.003] and 42 ± 40 vs. 11 ± 31 IU/mL [p = 0.005], respectively) than controls. The mean number of infectious complications was significantly lower after IVIG therapy in the IVIG group. IVIg was associated with restoration of humoral immunity in heart recipients with post-transplant IgG hypogammaglobulinemia and severe infections.

The prognostic value of hTERT expression levels in advanced-stage colorectal cancer patients: a comparison between tissue and serum expression

AIM: Telomeres are regions of highly repetitive, non-coding DNA located at the termini of chromosomes whose principal function is to maintain the structural stability of these ends. In 90% of human tumours, telomere length is maintained by the expression and activation of telomerase reverse transcriptase. Various studies have demonstrated an increase in telomerase activity in tumour tissue, which suggests its possible prognostic value. The main objective of our study was to study the prognostic value of the expression level of telomerase catalytic component (hTERT) in patients with colorectal cancer (CRC). METHODS: We analysed the prognostic value of the ratio of telomerase expression in tumour tissue to telomerase expression in the adjacent healthy mucosa and the prognostic value of the expression level of hTERT in the serum of patients diagnosed with CRC. As secondary objectives of the study, we (1) analysed the correlation between telomerase expression in the serum and that in the tumour tissue and (2) analysed the relationship between telomerase expression and different clinical parameters. RESULTS: Peripheral blood and tissue samples taken from 48 patients with CRC were analysed. No significant differences were observed in disease-free survival (DFS) or overall survival time (OST) between the groups of patients categorised based on the ratio of telomerase expression between tumour tissue and healthy tissue. The correlation index (Pearson's coefficient) between telomerase levels in the serum and those in tissue was 0.32. Our study of the relationship between telomerase levels in the serum and different clinical variables, such as tumour size, ganglion affectation, preoperative carcinoembryonic antigen levels and stage, revealed a higher telomerase expression level in patients with stage IV CRC. There was no significant association between telomerase expression in tumour tissue and the clinical parameters analysed. CONCLUSIONS: The results obtained in our study do not allow us to propose that the level of telomerase expression be used as a prognostic factor in colorectal cancer. Thus, we cannot consider telomerase expression in the serum as a surrogate marker of its expression in tumour tissue (AU)

Immunophenotypic abnormalities of CD8+ T-cell subsets in a patient with unusual Good's Syndrome

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Role of polymorphisms in the TNFRSF13B (TACI) gene in Spanish patients with immunoglobulin A deficiency.

Mutations in the TNFRSF13B (TACI) gene have been associated with common variable immunodeficiency, and a role in immunoglobulin A deficiency (IgAD) has also been suggested. We aimed at studying the role of several polymorphisms along this gene in IgAD susceptibility. Three TNFRSF13B mutations (C104R, A181E and R202H) and eight additional single nucleotide polymorphisms in the gene were genotyped in 338 Spanish IgAD patients and 553 ethnically matched healthy controls and tested for association. Data from parents of 114 IgAD patients were also collected and used for additional analysis. No statistically significant differences were observed after comparing patients and controls for any single nucleotide polymorphism analysed. Therefore, our work seems to discard a role of TNFRSF13B mutations in IgAD, concordantly with the most recent published studies.

Controversias en torno al tiempo de psicosis no tratada como variable pronóstica independiente del curso evolutivo de las psicosis esquizofrénicas / Controversies about duration of untreated psychosis as independent prognostic variable of the evolutive course of schizophrenic psychoses

El objetivo del presente trabajo es detallar aquellos aspectos, a nuestro entender más relevantes, extraídos de la creciente literatura sobre el tiempo de psicosis no tratada (DUP), incidiendo sobre dos aspectos nucleares y objeto de una creciente controversia, como son: a) aquellas razones que a lo largo de la última década han llevado a catapultar el DUP a la primera plana de la investigación en el terreno de los primeros episodios psicóticos, y b) el papel último del DUP a la hora de vertebrar el diseño y las diferentes estrategias de actuación en los programas de intervención precoz sobre las psicosis. Se aportan datos correspondientes a la evaluación del DUP, como variable pronóstica independiente, en una muestra de 231 pacientes, con un diagnóstico de trastorno esquizofrénico y/o trastorno esquizofreniforme (criterios DSM-IV) y un seguimiento de 24 meses. La conclusión final es que el DUP funciona más como un marcador de riesgo que como una variable pronóstica independiente, determinante del curso evolutivo de las psicosis esquizofrénicas. En este sentido su papel dentro de los programas de intervención precoz en las psicosis debería revisarse

This study reviews recent literature on duration of untreated psychosis (DUP) and its most relevant characteristics and controversial issues, such as: a) why DUP has been pointed out as a main variable in first-episode psychosis research, and b) the role of DUP in designing intervention programs for the design and different action strategies in early intervention programs in psychoses. The authors also present data from a 2 year follow-up study of 231 patients with a diagnosis of schizophrenia and/or schizophreniform disorder (according to DSM-IV criteria). Results are included, analyzing DUP as prognostic factor for clinical outcome. Our conclusions suggest that DUP is a risk marker but not an independent prognostic factor determining follow-up in schizophrenic psychoses. Therefore, DUP's role in early intervention programs should be redefined

[Controversies about duration of untreated psychosis as independent prognostic variable of the evolutive course of schizophrenic psychoses]. / Controversias en torno al tiempo de psicosis no tratada como variable pronóstica independiente del curso evolutivo de las psicosis esquizofrénicas.

This study reviews recent literature on duration of untreated psychosis (DUP) and its most relevant characteristics and controversial issues, such as: a) why DUP has been pointed out as a main variable in first-episode psychosis research, and b) the role of DUP in designing intervention programs for the design and different action strategies in early intervention programs in psychoses. The authors also present data from a 2 year follow-up study of 231 patients with a diagnosis of schizophrenia and/or schizophreniform disorder (according to DSM-IV criteria). Results are included, analyzing DUP as prognostic factor for clinical outcome. Our conclusions suggest that DUP is a risk marker but not an independent prognostic factor determining follow-up in schizophrenic psychoses. Therefore, DUP's role in early intervention programs should be redefined.

Neurocognitive functioning in Lesch-Nyhan disease and partial hypoxanthine-guanine phosphoribosyltransferase deficiency.

Lesch-Nyhan disease (LND) is a rare, X-linked genetic disorder that involves the nearly complete absence of an enzyme (hypoxanthine-guanine phosphoribosyltransferase, or HPRT) that is essential for purine salvage. In addition to hyperuricemia, all patients with classic LND suffer from movement disorder and compulsive self-injury, and most have mental retardation. Patients with partial HPRT deficiency (variants) always have hyperuricemia and often have neurologic abnormalities, but do not self-injure and usually are described as having normal intelligence. Here we compare 15 patients with LND to 9 variants and 13 normal adolescents and adults. Testing revealed unambiguous and qualitatively similar cognitive deficits in both patient groups. The variants produced scores that were intermediate between those of patients with LND and normal participants on nearly every cognitive measure. We discuss these findings in terms of what is known about the neuropathology of LND.

[Training in social skills in patients with acquired brain damage]. / Entrenamiento en habilidades sociales en pacientes con daño cerebral adquirido.

INTRODUCTION: Brain damaged patients have cognitive deficits, behaviour disorders and personality changes which affect socio-familial behaviour. Frequently, these changes generate considerable disturbance between family members and make it very difficult to return to work. OBJECTIVE: We describe a pilot study which led to the development and application of a focal rehabilitation programme aimed at retraining this group in social skills. PATIENTS AND METHODS: The programme was intensive (3 months) and included 6 outpatients (5 men and 1 woman) who took part in programmes of neuropsychological rehabilitation after traumatic or vascular cerebral lesions (X = 19.2 months after the lesion occurred). The average age of the patients was 27.2 years and their average IQ 109.2. Individual and group interventions were combined (role-playing, 'make-believe' work, video filming) emphasizing particularly the processes of learning without making mistakes and the extension of achievements to the natural setting (controlled trials). RESULTS AND CONCLUSIONS: We state and describe the relationship between the nature of neuropsychological and psychopathological deficits, and the characteristics of the limitations in social behaviour. The patients showed a significant reduction in the level of anxiety and aggressive behaviour and improvement in consciousness of their defects. Some improvement was seen in expressing opinions and emotions, and in ability to adapt social conduct to different situations (flexible behaviour). Finally we describe the conclusions drawn as to this treatment for future review and improvement of the programme.

Entrenamiento en habilidades sociales en pacientes con daño cerebral adquirido / Training in social skill in patients with acquired brain damage

Introduction. Brain damaged patients have cognitive deficits, behaviour disorders and personality changes which affect socio-familial behaviour. Frequently, these changes generate considerable disturbance between family members and make it very difficult to return to work. Objective. We describe a pilot study which led to the development and application of a focal rehabilitation programme aimed at retraining this group in social skills. Patients and methods. The programme was intensive (3 months) and included 6 outpatients (5 men and 1 woman) who took part in programmes of neuropsychological rehabilitation after traumatic or vascular cerebral lesions (X= 19.2 months after the lesion occurred). The average age of the patients was 27.2 years and their average IQ 109.2. Individual and group interventions were combined (role-playing, ‘makebelieve’ work, video filming) emphasizing particularly the processes of learning without making mistakes and the extension of achievements to the natural setting (controlled trials). Results and conclusions. We state and describe the relationship between the nature of neuropsychological and psychopathological deficits, and the characteristics of the limitations in social behaviour. The patients showed a significant reduction in the level of anxiety and aggressive behaviour and improvement in consciousness of their defects. Some improvement was seen in expressing opinions and emotions, and in ability to adapt social conduct to different situations (flexible behaviour). Finally we describe the conclusions drawn as to this treatment for future review and improvement of the programme (AU)

Introducción. Los pacientes con daño cerebral presentan déficit cognitivos, conductuales y cambios de personalidad que condicionan su funcionamiento sociofamiliar. Estos cambios generan con frecuencia enorme malestar entre familiares y representan serias dificultades para el restablecimiento de la actividad laboral. Objetivo. Describir una experiencia piloto que supuso el desarrollo y aplicación de un programa de rehabilitación focal dirigido al reentrenamiento de las habilidades sociales de este colectivo. Pacientes y métodos. El programa intensivo (3 meses) contó con seis pacientes ambulatorios (5 varones y 1 mujer), participantes en programas de rehabilitación neuropsicológica tras sufrir lesiones cerebrales de origen traumático o vascular (X= 19,2 meses desde la lesión). La media de edad era de 27,2 años y el CI medio de 109,2. Se combinaron intervención individual y grupal (role-playing, trabajo de supuestos, filmación en vídeo), poniendo especial hincapié en los procesos de aprendizaje sin error y en la generalización de los logros al entorno natural (ensayos controlados). Resultados y conclusiones. Se comprueba y describe la relación existente entre la naturaleza de los déficit neuropsicológicos y psicopatológicos y las características de las limitaciones en el funcionamiento social. Los pacientes mostraron una significativa reducción del nivel de ansiedad y de conductas agresivas y una mejora de la conciencia sobre los déficit. Asimismo, se observó una discreta mejora en la expresión de opiniones y emociones, y en la capacidad de adecuar la conducta social a las diferentes situaciones (flexibilidad conductual). Finalmente, se describen las conclusiones terapéuticas que extrajo el equipo para la futurarevisión y mejora del programa (AU)

Tiroidectomía: Una modificación de la técnica / Thyroidectomy: a modification of the technique

Se describe una modificación a la técnica de la tiroidectomía, que facilita la intervención y acorta el tiempo operatorio. Se señalan los buenos resultados obtenidos en 20 casos. El procedimiento no requiere cortar los músculos pretiroideos. Se comienza por la sección del istmo y se libera la glándula por su cara profunda, separándola de la superficie laringotraqueal. Una vez liberado el lóbulo es más fácil la ligadura y sección de sus pedículos vasculares. Se describe la forma de evitar las lesiones de los nervios laríngeos y glándulas paratiroides. Su indicación principal es el tratamiento de los nódulos del tiroides(AU)