The impact of comorbidities and their stacking on short- and long-term prognosis of patients over 50 with community-acquired pneumonia.

BACKGROUND: The prognosis of patients hospitalized with community-acquired pneumonia (CAP) with regards to intensive care unit (ICU) admission, short- and long-term mortality is correlated with patient's comorbidities. For patients hospitalized for CAP, including P-CAP, we assessed the prognostic impact of comorbidities known as at-risk (AR) or high-risk (HR) of pneumococcal CAP (P-CAP), and of the number of combined comorbidities. METHODS: Data on hospitalizations for CAP among the French 50+ population were extracted from the 2014 French Information Systems Medicalization Program (PMSI), an exhaustive national hospital discharge database maintained by the French Technical Agency of Information on Hospitalization (ATIH). Their admission diagnosis, comorbidities (nature, risk type and number), other characteristics, and their subsequent hospital stays within the year following their hospitalization for CAP were analyzed. Logistic regression models were used to assess the associations between ICU transfer, short- and 1-year in-hospital mortality and all covariates. RESULTS: From 182,858 patients, 149,555 patients aged ≥ 50 years (nonagenarians 17.8%) were hospitalized for CAP in 2014, including 8270 with P-CAP. Overall, 33.8% and 90.5% had ≥ 1 HR and ≥ 1 AR comorbidity, respectively. Cardiac diseases were the most frequent AR comorbidity (all CAP: 77.4%). Transfer in ICU occurred for 5.4% of CAP patients and 19.4% for P-CAP. Short-term and 1-year in-hospital mortality rates were 10.9% and 23% of CAP patients, respectively, significantly lower for P-CAP patients: 9.2% and 19.8% (HR 0.88 [95% CI 0.84-0.93], p < .0001). Both terms of mortality increased mostly with age, and with the number of comorbidities and combination of AR and HR comorbidities, in addition of specific comorbidities. CONCLUSIONS: Not only specific comorbidities, but also the number of combined comorbidities and the combination of AR and HR comorbidities may impact the outcome of hospitalized CAP and P-CAP patients.

Reasons for intravesical instillation postponement during adjuvant treatment of non-muscle-invasive bladder cancer: A prospective study.

INTRODUCTION: Intravesical instillations for adjuvant treatment of non-muscle-invasive bladder cancer (NMIBC) may be postponed of necessity. However, the frequency and reasons for postponement are unclear. MATERIALS: We carried out a prospective, epidemiological study in an Urology department of the Île-de-France, between August 2016 and March 2017, to determine the frequency and reasons for postponement of intravesical instillations during adjuvant treatment of NMIBC. One-hundred consecutive patients treated by intravesical instillations of mitomycin C (MMC) or Bacillus Calmette-Guérin (BCG) were included. At each session and in case of instillation postponement, the medical team completed a specially designed questionnaire. RESULTS: A total of 541 instillations were performed in the 100 patients. Twenty-four instillations (4.4%) were postponed in 19 patients. The major cause of postponement was an untreated positive urine analysis and culture (UAC) in 13/24 (54%) cases. The causes of cancellation did not differ significantly between MMC and BCG. The most frequently cancelled instillations were the first in the therapeutic protocol in 26% of cases. The number of instillations preceding those cancelled did not differ significantly between MMC and BCG (2.1±2.0 instillations for MMC vs. 1.5±1.6 for BCG; P=0.64). CONCLUSIONS: There was a low rate of postponed instillations (4.4%). The main reasons, namely an untreated UAC and a positive dipstick test, based on the jurisprudence, are not included in the latest CC-AFU guidelines. LEVEL OF EVIDENCE: 3.

French adaptation of the "Frenchay Dysarthria Assessment 2" speech intelligibility test.

OBJECTIVES: Speech intelligibility can be defined as "the degree to which a speaker's intended message is recovered by a listener". Loss of intelligibility is one of the most frequent complaints in patients suffering from speech disorder, impairing communication. Measurement of intelligibility is therefore an important parameter in follow-up. We developed a French version of the "Frenchay Dysarthria Assessment, 2nd edition" (FDA-2), an intelligibility test recognized internationally in its English version. The present study details the construction of the test and its preliminary validation. MATERIALS AND METHODS: We first compiled a set of words and phrases in French, based on the criteria defined in FDA-2. In a second step, we validated the test in healthy subjects in normal and noisy conditions, to check sensitivity to speech signal degradation. RESULTS: The test proved valid and sensitive, as scores were significantly lower for noise-degraded stimuli. CONCLUSION: This French-language intelligibility test can be used to evaluate speech disorder: for example, in dysarthria, head and neck cancer or after cochlear implantation.

FIVHeMA: Intraventricular fibrinolysis versus external ventricular drainage alone in aneurysmal subarachnoid hemorrhage: A randomized controlled trial.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke, which often causes acute hydrocephalus requiring the insertion of an external ventricular drain (EVD). A major complication of aneurysmal SAH is delayed cerebral ischemia (DCI). As DCI is linked to the presence of blood within the subarachnoid space, it has been hypothesized that removing this blood may decrease the risk of DCI. This could be achieved by injecting a fibrinolytic agent through the EVD, a strategy called intraventricular fibrinolysis (IVF). Here, we propose to conduct a phase III trial to directly evaluate the impact of IVF after aneurysmal SAH. MATERIALS AND METHODS: We will perform an open-label randomized controlled trial comparing the standard of care, i.e. EVD alone, to the experimental treatment, i.e. IVF. We plan to include 440 patients to be able to show a 10% increase in the rate of good functional outcomes in the EVD+IVF group compared to the EVD alone group (α=0.05 and ß=0.8). To obtain such sample, a multicenter trial is required, and to date 17 research sites in France have agreed to participate. PERSPECTIVE: FIVHeMA would be the first phase III trial evaluating the relevance of IVF in aneurysmal SAH. If IVF is shown to be beneficial, then a new therapeutic tool will be available to improve the outcomes of aneurysmal SAH patients.

Relevance of TSH evaluation in elderly in-patients with non-thyroidal illness.

BACKGROUND: Non-thyroidal illness (NTI) is frequent in hospitalized patients. Its recovery is characterized by a raise in TSH levels. However, the clinical significance of high TSH levels at admission in hospitalized elderly patients with NTI remains uncertain. AIM: To explore the relevance of baseline TSH evaluation in hospitalized elderly patients with NTI. METHODS: We examined the participants with NTI (n = 123) from our previous study (Sforza, 2017). NTI was defined as: low T3 (< 80 ng/dL) and normal or low total T4 in the presence of TSH values between 0.1 and 6.0 mU/L. Thyroid function tests were performed on day 1 and day 8 of the hospital stay. Positive TSH changes (+ ΔTSH) were considered when the day-8 TSH value increased more than the reference change value for TSH (+ 78%). Multiple logistic regression was used to evaluate the independent association of baseline TSH, sex, clinical comorbidities (by ACE-27) and medications with + ΔTSH. RESULTS: Out of 123 patients (77 ± 8 years, 52% female), 34 showed a + ΔTSH. These patients had a lower TSH at admission (p < 0.001) and intra-hospital mortality (p = 0.003) than the others. In multiple logistic regression, TSH > 2.11 mU/L at baseline was associated with reduced odds to show + ΔTSH [odds ratio (95 CI) 0.29 (0.11-0.75); p = 0.011] in a model adjusted by age, sex and ACE-27. DISCUSSION: Inappropriately higher TSH levels at admission in hospitalized elderly patients were associated with a reduced ability to raise their TSH levels later on. The present results confront the idea that TSH levels at admission are irrelevant in this clinical context.

Hypothyroidism in hospitalized elderly patients: a sign of worse prognosis.

PURPOSE: Overt hypothyroidism has adverse clinical consequences and might worsen prognosis in critically ill elderly patients. However, the difficult interpretation of thyroid function tests (TFT) due to non-thyroidal illness (NTI) has led to discouragement of screening for thyroid dysfunction. Our aim was to determine the prevalence of TFT compatible with hypothyroidism and to study its influence on mortality among hospitalized elderly patients. METHODS: In this prospective study we consecutively included all patients ≥60 years admitted by the Internal Medicine Department to the hospital ward (n = 451) of the Cesar Milstein Hospital in Buenos Aires, Argentina. TFT were done on day 1 and 8. Thyroid function categories were defined as overt and subclinical hypothyroidism, overt and subclinical hyperthyroidism, euthyroidism and NTI. Stage of chronic kidney disease (CKD), Adult Comorbidity Evaluation (ACE)-27, and intra-hospital mortality were recorded. The association between mortality and TFT categories was studied by Cox regression. RESULTS: Out of 451 patients (77.0 ± 7.9 years, 54% females) 76% were categorized as NTI, 4% as overt hypothyroid, 10% as subclinical hypothyroid, 1% as subclinical hyperthyroid and 9% as euthyroid. Overt hypothyroid patients showed significantly higher mortality than the rest of the groups (25%, p < 0.05) while ACE-27 was similar among all of them (p = 0.658). In addition, patients within the overt hypothyroid category showed a higher mortality rate than NTI in a model adjusted by Stage 5-CKD, ACE-27, sex and age [HR 3.1 (1.14-8.41), p < 0.026]. CONCLUSION: Overt hypothyroidism during hospitalization was associated with elevated mortality. Further studies would reveal if TFT alterations compatible with hypothyroidism should be diagnosed/treated in hospitalized elderly patients.

FDG PET-CT for solitary pulmonary nodule and lung cancer: Literature review.

The investigation of solitary pulmonary nodule (SPN) and non-small cell lung cancer (NSCLC) has rapidly become one of the main indications for 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), currently combined with computed tomography (PET-CT). In this literature review, we first attempt to clarify how PET imaging contributes to investigating SPN, in conjunction with conventional CT. We highlight the prospects of research underway to improve our understanding of SPN. In the second part of this review, we analyze the current role of PET-CT in the overall care process for lung cancer. We review the indications for which consensus has been reached, for example initial staging, as well as new indications such as radiation therapy planning or prognostic assessment.

Comment on "Acoustical observation of bubble oscillations induced by bubble popping".

We have reproduced the experiment of acoustic monitoring of spontaneous popping of single soap bubbles standing in air reported by Ding et al. [2aaPhys. Rev. E 75, 041601 (2007)]. By using a single microphone and two different signal acquisition systems recording in parallel the signal at the microphone output, among them the system used by Ding et al., we have experimentally evidenced that the acoustic precursors of bubble popping events detected by Ding et al. actually result from an acausal artifact of the signal processing performed by their acquisition system which lies outside of its prescribed working frequency range. No acoustic precursor of popping could be evidenced with the microphone used in these experiments, whose sensitivity is 1VPa-1 and frequency range is 500 Hz-100 kHz.

Análisis de características clínicas y ecográficas de nódulos tiroideos con citología Bethesda III y su evolución / Analysis of Clinical and Ultrasound Features of Thyroid Nodules With Bethesda III Cytology and their Evolution

Introducción: Desde la implementación de la clasificación citológica de los nódulos tiroideos por el sistema Bethesda en 6 categorías, el grupo Bethesda III (BIII) es el que genera más controversias en cuanto a la conducta de seguimiento. Según la literatura corresponden a esta categoría entre el 4 y 20 % de los nódulos punzados y conllevan un riesgo de malignidad del 5-15 %. Objetivo: Determinar características clínicas y ecográficas de los nódulos tiroideos clasificados como BIII en nuestra población y analizar su evolución en el tiempo. Materiales y Métodos: Estudio descriptivo de todos los pacientes enviados a PAAF bajo guía ecográfica que resultaron BIII, entre febrero 2011 y diciembre 2013. Se describieron las características clínicas y ecográficas de dichos nódulos y su evolución. La mediana de seguimiento fue 24 meses (rango: 2 a 35 meses). Resultados: Fueron punzados 945 nódulos de 784 pacientes. Se clasificaron como BIII 85 nódulos (8,99 %) de 72 pacientes (69 mujeres y 3 varones), con una media de edad de 71,1 ±7,1 años. La mediana del diáme­tro mayor de los nódulos fue 18 mm (9 a 54 mm). El 76,1 % de los nódulos fueron sólidos, el 22,5 % mixtos y en 1 caso espongiforme. Según el patrón ecográfico: 36,7 % eran hipoecoicos, 54,4 % isoecoicos y 8,9 % hiperecoicos. El 8,33 % presentó microcalcificaciones y el 9,9 % márgenes irregulares. El 39,43 % presentó vascularización periférica, 4,23 % central y 56,34 % mixta. Evolución: De los 72 pacientes, 9 (12,1 %) se perdieron en el seguimiento, a 56 (77,8 %) se los siguió clínica y ecográficamente, y en 7 pacientes (9,7 %) se tomó conducta quirúrgica basándose en criterios clínicos y ecográficos sospechosos de malignidad, o por antecedentes familiares positivos, resultando 3 con carcinoma papilar (CP), y 4 con patología benigna. Durante el seguimiento, Fueron repunzados 40 nódulos de 35 pacientes (48,6 %) que resultaron: 2 BI, 23 BII, 14 BIII y 1 BV. De los 14 nódulos con segunda punción BIII, se operaron 7, 1 CP y 6 patología benigna. El nódulo BV resultó un CP a su cirugía. En total, fueron operados 16 pacientes con BIII (22,2 %) (7 de inicio y 8 luego de la segunda PAAF y 1 en el seguimiento clínico ecográfico), de los cuales 5 (31,25 %) resultaron CP y 11 (68,75 %) patología tiroidea benigna. Conclusión: Si bien para los nódulos tiroideos con categoría BIII se recomienda generalmente una repunción, en nuestra experiencia el hallazgo de características clínicas y ecográficas sospechosas de malignidad y/o antecedentes familiares de cáncer de tiroides permitiría en algunos pacientes optar por la cirugía tiroidea desde el inicio. Rev Argent Endocrinol Metab 52:14-21, 2015 Los autores declaran no poseer conflictos de interés.

Background: Since the implementation of the Bethesda System for cytology classification of thyroid nodules into 6 categories, the Bethesda III group (B III) has been the most controversial as regards follow-up management. Reported data shows that about 4 to 20 % of all biopsied nodules belong to this category, with the risk of malignancy being 5 to 15 %. Objective: To determine clinical and sonographic features of thyroid nodules classified as BIII in our population and analyze their evolution over time. Methods: We determined the clinical and ultrasonographic (US) features of all patients who had undergone fine needle aspiration biopsy (FNAB) in 2011-2013 at our Institution for Retirees and Pensioners. Descriptive study of all patients with nodules classified as BIII with a median follow-up time of 24 months (2 to 35 months). Results: Out of 945 nodules from 784 patients biopsied (age, mean ± SD:71.1±7.1 years), 85 (8.99 %) were classified as BIII. Six patients had received neck radiation, and 5 reported family history of thyroid cancer. The median (range) largest diameter of nodules was 18 mm (9-54 mm). Fifty-four nodules (76.1 %) were solid, 16 (22.5 %) mixed, and 1 spongiform. Based on echogenicity, 36.7 % were hypoechoic, 54.4 % isoechoic and 8.9 % hyperechoic. Twenty-two nodules (25.88 %) were taller than wider, 8.33 % had microcalcifications and 9.9 % had irregular margins. At Doppler evaluation, 39.43 % of nodules had peripheral vascularity, 4.23 % showed central vascularity and 56.34 % had mixed vascularity. In 7 out of 72 patients with BIII classification, surgery was indicated at the start based on suspicious clinical and US findings for malignancy, or family history of thyroid cancer. Out of these 7 patients, 3 were found to have papillary carcinoma (PTC), 1 follicular adenoma (FA), 1 colloid goiter (CG), 1 adenomatous nodule (AN) and 1 chronic lymphocytic thyroiditis (CLT). As regards the follow-up and evolution of the rest of the group, 9 were lost, 21 remained in observation and 35 (48.6 %) with 40 nodules underwent a second FNAB, with the following results: 2 BI, 23 BII, 14 BIII and 1 BV. Out of 14 nodules confirmed as BIII on repeat FNAB, 7 were operated on, resulting in: 2 CLT, 3 CG, 1 FA and 1 PTC. The BV nodule proved to be PTC. A total of 16 patients with BIII nodules underwent surgery (7 initially, 8 after a second FNAB, and 1 during clinical and US follow-up) and 5 (31.25 %) were PTC while 11 (68.75 %) were benign. Conclusion: Even though BIII thyroid nodules generally require a second FNAB, in our experience clinical and US findings suspicious for malignancy, or family history of thyroid cancer could allow some patients to be offered surgery at initial presentation. Rev Argent Endocrinol Metab 52:14-21, 2015 No financial conflicts of interest exist.

Análisis de características clínicas y ecográficas de nódulos tiroideos con citología Bethesda III y su evolución / Analysis of Clinical and Ultrasound Features of Thyroid Nodules With Bethesda III Cytology and their Evolution

Introducción: Desde la implementación de la clasificación citológica de los nódulos tiroideos por el sistema Bethesda en 6 categorías, el grupo Bethesda III (BIII) es el que genera más controversias en cuanto a la conducta de seguimiento. Según la literatura corresponden a esta categoría entre el 4 y 20 % de los nódulos punzados y conllevan un riesgo de malignidad del 5-15 %. Objetivo: Determinar características clínicas y ecográficas de los nódulos tiroideos clasificados como BIII en nuestra población y analizar su evolución en el tiempo. Materiales y Métodos: Estudio descriptivo de todos los pacientes enviados a PAAF bajo guía ecográfica que resultaron BIII, entre febrero 2011 y diciembre 2013. Se describieron las características clínicas y ecográficas de dichos nódulos y su evolución. La mediana de seguimiento fue 24 meses (rango: 2 a 35 meses). Resultados: Fueron punzados 945 nódulos de 784 pacientes. Se clasificaron como BIII 85 nódulos (8,99 %) de 72 pacientes (69 mujeres y 3 varones), con una media de edad de 71,1 ±7,1 años. La mediana del diáme¡tro mayor de los nódulos fue 18 mm (9 a 54 mm). El 76,1 % de los nódulos fueron sólidos, el 22,5 % mixtos y en 1 caso espongiforme. Según el patrón ecográfico: 36,7 % eran hipoecoicos, 54,4 % isoecoicos y 8,9 % hiperecoicos. El 8,33 % presentó microcalcificaciones y el 9,9 % márgenes irregulares. El 39,43 % presentó vascularización periférica, 4,23 % central y 56,34 % mixta. Evolución: De los 72 pacientes, 9 (12,1 %) se perdieron en el seguimiento, a 56 (77,8 %) se los siguió clínica y ecográficamente, y en 7 pacientes (9,7 %) se tomó conducta quirúrgica basándose en criterios clínicos y ecográficos sospechosos de malignidad, o por antecedentes familiares positivos, resultando 3 con carcinoma papilar (CP), y 4 con patología benigna. Durante el seguimiento, Fueron repunzados 40 nódulos de 35 pacientes (48,6 %) que resultaron: 2 BI, 23 BII, 14 BIII y 1 BV. De los 14 nódulos con segunda punción BIII, se operaron 7, 1 CP y 6 patología benigna. El nódulo BV resultó un CP a su cirugía. En total, fueron operados 16 pacientes con BIII (22,2 %) (7 de inicio y 8 luego de la segunda PAAF y 1 en el seguimiento clínico ecográfico), de los cuales 5 (31,25 %) resultaron CP y 11 (68,75 %) patología tiroidea benigna. Conclusión: Si bien para los nódulos tiroideos con categoría BIII se recomienda generalmente una repunción, en nuestra experiencia el hallazgo de características clínicas y ecográficas sospechosas de malignidad y/o antecedentes familiares de cáncer de tiroides permitiría en algunos pacientes optar por la cirugía tiroidea desde el inicio. Rev Argent Endocrinol Metab 52:14-21, 2015 Los autores declaran no poseer conflictos de interés.(AU)

Background: Since the implementation of the Bethesda System for cytology classification of thyroid nodules into 6 categories, the Bethesda III group (B III) has been the most controversial as regards follow-up management. Reported data shows that about 4 to 20 % of all biopsied nodules belong to this category, with the risk of malignancy being 5 to 15 %. Objective: To determine clinical and sonographic features of thyroid nodules classified as BIII in our population and analyze their evolution over time. Methods: We determined the clinical and ultrasonographic (US) features of all patients who had undergone fine needle aspiration biopsy (FNAB) in 2011-2013 at our Institution for Retirees and Pensioners. Descriptive study of all patients with nodules classified as BIII with a median follow-up time of 24 months (2 to 35 months). Results: Out of 945 nodules from 784 patients biopsied (age, mean ± SD:71.1±7.1 years), 85 (8.99 %) were classified as BIII. Six patients had received neck radiation, and 5 reported family history of thyroid cancer. The median (range) largest diameter of nodules was 18 mm (9-54 mm). Fifty-four nodules (76.1 %) were solid, 16 (22.5 %) mixed, and 1 spongiform. Based on echogenicity, 36.7 % were hypoechoic, 54.4 % isoechoic and 8.9 % hyperechoic. Twenty-two nodules (25.88 %) were taller than wider, 8.33 % had microcalcifications and 9.9 % had irregular margins. At Doppler evaluation, 39.43 % of nodules had peripheral vascularity, 4.23 % showed central vascularity and 56.34 % had mixed vascularity. In 7 out of 72 patients with BIII classification, surgery was indicated at the start based on suspicious clinical and US findings for malignancy, or family history of thyroid cancer. Out of these 7 patients, 3 were found to have papillary carcinoma (PTC), 1 follicular adenoma (FA), 1 colloid goiter (CG), 1 adenomatous nodule (AN) and 1 chronic lymphocytic thyroiditis (CLT). As regards the follow-up and evolution of the rest of the group, 9 were lost, 21 remained in observation and 35 (48.6 %) with 40 nodules underwent a second FNAB, with the following results: 2 BI, 23 BII, 14 BIII and 1 BV. Out of 14 nodules confirmed as BIII on repeat FNAB, 7 were operated on, resulting in: 2 CLT, 3 CG, 1 FA and 1 PTC. The BV nodule proved to be PTC. A total of 16 patients with BIII nodules underwent surgery (7 initially, 8 after a second FNAB, and 1 during clinical and US follow-up) and 5 (31.25 %) were PTC while 11 (68.75 %) were benign. Conclusion: Even though BIII thyroid nodules generally require a second FNAB, in our experience clinical and US findings suspicious for malignancy, or family history of thyroid cancer could allow some patients to be offered surgery at initial presentation. Rev Argent Endocrinol Metab 52:14-21, 2015 No financial conflicts of interest exist.(AU)

The translation of recombinant proteins in E. coli can be improved by in silico generating and screening random libraries of a -70/+96 mRNA region with respect to the translation initiation codon.

Recombinant protein translation in Escherichia coli may be limited by stable (i.e. low free energy) secondary structures in the mRNA translation initiation region. To circumvent this issue, we have set-up a computer tool called 'ExEnSo' (Expression Enhancer Software) that generates a random library of 8192 sequences, calculates the free energy of secondary structures of each sequence in the -70/+96 region (base 1 is the translation initiation codon), and then selects the sequence having the highest free energy. The software uses this 'optimized' sequence to create a 5' primer that can be used in PCR experiments to amplify the coding sequence of interest prior to sub-cloning into a prokaryotic expression vector. In this article, we report how ExEnSo was set-up and the results obtained with nine coding sequences with low expression levels in E. coli. The free energy of the -70/+96 region of all these coding sequences was increased compared to the non-optimized sequences. Moreover, the protein expression of eight out of nine of these coding sequences was increased in E. coli, indicating a good correlation between in silico and in vivo results. ExEnSo is available as a free online tool.

[Ultrasound and CT study of duodenal pathology]. / Ecografía y tomografía computarizada de la patología duodenal.

The radiological evaluation of the duodenum has traditionally been based on barium transit studies; however, ultrasound (US) and computed tomography (CT) are becoming more important in the assessment of this portion of the intestine and the structures that surround it. This report describes and illustrates the CT and US findings for different entities that affect the duodenum, including diseases of the duodenum itself and those of neighboring organs that affect this portion of the small intestine. We classify the pathologies by etiology into congenital, traumatic, iatrogenic and foreign bodies, bezoars, hematologic, inflammatory and neoplastic. Moreover, we present the incidental duodenal and periduodenal findings in US and CT that radiologists should be familiar with given the widespread use of these techniques.

Ecografía y tomografía computarizada de la patología duodenal / Ultrasound and CT study of duodenal pathology

El análisis radiológico del duodeno se ha basado tradicionalmente en el tránsito baritado, pero actualmente la ecografía y la tomografía computarizada (TC) están adquiriendo cada vez más importancia para valorar este tramo intestinal y las estructuras que lo rodean. En este trabajo se presentan los hallazgos en TC y ecografía de diversas entidades que afectan al duodeno, tanto por alteraciones propias, como por patología de órganos vecinos que afecten a este tramo intestinal. Para ello se han clasificado como patología congénita, traumática, iatrogénica y cuerpos extraños, bezoares, patología hematológica, inflamatoria y neoplásica. Además, se presentan los hallazgos incidentales duodenales y periduodenales en ecografía y TC que, dado el uso frecuente de estas técnicas, es necesario conocer

The radiological evaluation of the duodenum has traditionally been based on barium transit studies; however, ultrasound (US) and computed tomography (CT) are becoming more important in the assessment of this portion of the intestine and the structures that surround it. This report describes and illustrates the CT and US findings for different entities that affect the duodenum, including diseases of the duodenum itself and those of neighboring organs that affect this portion of the small intestine. We classify the pathologies by etiology into congenital, traumatic, iatrogenic and foreign bodies, bezoars, hematologic, inflammatory and neoplastic. Moreover, we present the incidental duodenal and periduodenal findings in US and CT that radiologists should be familiar with given the widespread use of these techniques

Dysregulation of IL-2/IL-2R system alters proliferation of early activated CD4+ T cell subset in patients with end-stage renal failure.

BACKGROUND/AIM: Although CD4+ T cells are preactivated in patients with end-stage renal failure (ESRF), these patients present an impairment of T cell immune response, which is partly responsible for the higher incidence of infection in this population. The aim of the present study was to analyze the mechanisms underlying the altered function of activated CD4+ T cells in patients with ESRF. METHODS: Thirty patients undergoing chronic hemodialysis (HD) and 20 patients with ESRF were compared with 15 sex- and age-matched controls. CD4+ T cell early activation (CD69, CD25), interleukin-2 (IL-2)/IL-2 receptor (IL-2R) system, and proliferation capacity of CD69+/CD4+ T cells were assessed ex vivo after blood draw sampling, in culture conditions and after phytohemagglutinin (PHA) stimulation. RESULTS: Although the CD4+ T cell count was lower in chronic HD patients than in predialysis patients and controls (p = 0.007), CD4+ T cells showed a pre-activation state as demonstrated by higher percentage of CD69+/CD4+ T cells and CD25+/CD4+ T cells in chronic HD patients compared with the other groups ex vivo. Furthermore, CD69+/CD4+ T cells from chronic HD patients spontaneously released more IL-2 (22 +/- 6 pg/ml) than those from pre-dialysis patients (12 +/- 4 pg/ml, p = 0.005) and controls (5 +/- 3 pg/ml, p = 0.001). However, after PHA stimulation, CD69+/CD4+ T cells from chronic HD patients expressed lower cell surface CD25 density, and were unable to show further activation. Indeed, these cells produced less IL-2 and released more soluble IL-2R, and correlatively with IL-2 production, they showed lower proliferation capacity compared with predialysis patients (p = 0.001) and controls (p < 0.001). They also displayed decreased responsiveness to exogenous human recombinant IL-2. The restoration of the PHA stimulation index of CD69+/CD4+ T cells from chronic HD patients in the presence of normal human serum as well as the decreased stimulation index of CD69+/CD4+ T cells from control subjects incubated with HD serum, strongly suggest that uremic toxins and mediators induced by HD affect the IL-2/IL-2R pathway. CONCLUSION: These findings demonstrate the presence, in chronic HD patients, and to lesser extent, in predialysis patients, of abnormally high proportion of spontaneously preactivated CD4+ T cells whose proliferation and further activation are blunted due to dysregulation of the IL-2/IL-2R system.

Refinement of severely incomplete structures with maximum likelihood in BUSTER-TNT.

BUSTER-TNT is a maximum-likelihood macromolecular refinement package. BUSTER assembles the structural model, scales observed and calculated structure-factor amplitudes and computes the model likelihood, whilst TNT handles the stereochemistry and NCS restraints/constraints and shifts the atomic coordinates, B factors and occupancies. In real space, in addition to the traditional atomic and bulk-solvent models, BUSTER models the parts of the structure for which an atomic model is not yet available ('missing structure') as low-resolution probability distributions for the random positions of the missing atoms. In reciprocal space, the BUSTER structure-factor distribution in the complex plane is a two-dimensional Gaussian centred around the structure factor calculated from the atomic, bulk-solvent and missing-structure models. The errors associated with these three structural components are added to compute the overall spread of the Gaussian. When the atomic model is very incomplete, modelling of the missing structure and the consistency of the BUSTER statistical model help structure building and completion because (i) the accuracy of the overall scale factors is increased, (ii) the bias affecting atomic model refinement is reduced by accounting for some of the scattering from the missing structure, (iii) the addition of a spatial definition to the source of incompleteness improves on traditional Luzzati and sigmaA-based error models and (iv) the program can perform selective density modification in the regions of unbuilt structure alone.

[Retroperitoneal fibrosis, an unrecognized inflammatory disease. Clinical observations and review of the literature]. / La fibrose rétropéritonéale, une maladie inflammatoire méconnue. Observations cliniques et revue de la littérature.

Retroperitoneal fibrosis (RF) is a rare disease, typically with an insidious clinical course. The peak incidence is seen in patients 40 to 60 years of age and mostly in man. The characteristic finding in this disease is a periaortic fibrous mass that often surrounds the ureters. Although usually regarded as an obstructive uropathy, there has been growing recognition of the condition as a generalized disease. It may have a wide variety of manifestations including mediastinitis, thyroiditis and sclerosing cholangitis. The most common mode of presentation remains abdominal or flank pain with uremia, anemia and a high sedimentation rate. Although ultrasound and renal scintigraphy may contribute to the general evaluation of patients with RF, CT-scanner is the preferred imaging method. The multiplanar imaging capability of magnetic resonance may facilitate assessment of disease extent. The pathogenesis of the disease remains unknown. Steroids and, more recently tamoxifen, appear to be effective in the treatment of the RF. In most instances, RF does not lead to long-term morbidity or affect survival. The three cases of RF reported herein illustrate the varied mode of presentation and the response to the treatment.

High-resolution experimental phases for tryptophanyl-tRNA synthetase (TrpRS) complexed with tryptophanyl-5'AMP.

Native data, anomalous data at three wavelengths and an independent peak-wavelength data set for SeMet-substituted protein have been collected from cryoprotected crystals of the TrpRS-adenylate product (TAM) complex to a resolution limit of 1.7 A. Independent phase sets were developed using SHARP and improved by solvent flipping with SOLOMON using molecular envelopes derived from experimental densities for, respectively, peak-wavelength SAD data from four different crystals, MAD data and their M(S)IRAS combinations with native data. Hendrickson-Lattman phase-probability coefficients from each phase set were used in BUSTER to drive maximum-likelihood refinements of well defined parts of the previously refined room-temperature 2.9 A structure. Maximum-entropy completion followed by manual rebuilding was then used to generate a model for the missing segments, bound ligand and solvent molecules. Surprisingly, peak-wavelength SAD experiments produced the smallest phase errors relative to the refined structures. Selenomethionylated models deviate from one another by 0.25 A and from the native model by 0.38 A, but all have r.m.s. deviations of approximately 1.0 A from the 2.9 A model. Difference Fourier calculations between amplitudes from the 300 K experiment and the new amplitudes at 100 K using 1.7 A model phases show no significant structural changes arising from temperature variation or addition of cryoprotectant. The main differences between low- and high-resolution structures arise from correcting side-chain rotamers in the core of the protein as well as on the surface. These changes improve various structure-validation criteria.

Involvement of phosphatidylinositol 3-kinase and mitogen-activated protein kinases in glycine-extended gastrin-induced dissociation and migration of gastric epithelial cells.

The various molecular forms of gastrin can act as promoters of proliferation and differentiation in different regions of the gastrointestinal tract. We report a novel stimulatory effect of glycine-extended gastrin(17) only on cell/cell dissociation and cell migration in a non-tumorigenic mouse gastric epithelial cell line (IMGE-5). In contrast, both amidated and glycine-extended gastrin(17) stimulated proliferation of IMGE-5 cells via distinct receptors. Glycine-extended gastrin(17)-induced dissociation preceded migration and was blocked by selective inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) but did not require mitogen-activated protein (MAP) kinase activation. Furthermore, glycine-extended gastrin(17) induced a PI3-kinase-mediated tyrosine phosphorylation of the adherens junction protein beta-catenin, partial dissociation of the complex between beta-catenin and the transmembrane protein E-cadherin, and delocalization of beta-catenin into the cytoplasm. Long lasting activation of MAP kinases by glycine-extended gastrin(17) was specifically required for the migratory response, in contrast to the involvement of a rapid and transient MAP kinase activation in the proliferative response to both amidated and glycine-extended gastrin(17). Therefore, the time course of MAP kinase activation appears to be a critical determinant of the biological effects mediated by this pathway. Together with the involvement of PI3-kinase in the dissociation of adherens junctions, long term activation of MAP kinases seems responsible for the selectivity of this novel effect of G(17)-Gly on the adhesion and migration of gastric epithelial cells.