β-Lactam Monotherapy vs β-Lactam-Macrolide Combination Treatment in Moderately Severe Community-Acquired Pneumonia: A Randomized Noninferiority Trial.

IMPORTANCE: The clinical benefit of adding a macrolide to a β-lactam for empirical treatment of moderately severe community-acquired pneumonia remains controversial. OBJECTIVE: To test noninferiority of a β-lactam alone compared with a β-lactam and macrolide combination in moderately severe community-acquired pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Open-label, multicenter, noninferiority, randomized trial conducted from January 13, 2009, through January 31, 2013, in 580 immunocompetent adult patients hospitalized in 6 acute care hospitals in Switzerland for moderately severe community-acquired pneumonia. Follow-up extended to 90 days. Outcome assessors were masked to treatment allocation. INTERVENTIONS: Patients were treated with a β-lactam and a macrolide (combination arm) or with a β-lactam alone (monotherapy arm). Legionella pneumophila infection was systematically searched and treated by addition of a macrolide to the monotherapy arm. MAIN OUTCOMES AND MEASURES: Proportion of patients not reaching clinical stability (heart rate <100/min, systolic blood pressure >90 mm Hg, temperature <38.0°C, respiratory rate <24/min, and oxygen saturation >90% on room air) at day 7. RESULTS: After 7 days of treatment, 120 of 291 patients (41.2%) in the monotherapy arm vs 97 of 289 (33.6%) in the combination arm had not reached clinical stability (7.6% difference, P = .07). The upper limit of the 1-sided 90% CI was 13.0%, exceeding the predefined noninferiority boundary of 8%. Patients infected with atypical pathogens (hazard ratio [HR], 0.33; 95% CI, 0.13-0.85) or with Pneumonia Severity Index (PSI) category IV pneumonia (HR, 0.81; 95% CI, 0.59-1.10) were less likely to reach clinical stability with monotherapy, whereas patients not infected with atypical pathogens (HR, 0.99; 95% CI, 0.80-1.22) or with PSI category I to III pneumonia (HR, 1.06; 95% CI, 0.82-1.36) had equivalent outcomes in the 2 arms. There were more 30-day readmissions in the monotherapy arm (7.9% vs 3.1%, P = .01). Mortality, intensive care unit admission, complications, length of stay, and recurrence of pneumonia within 90 days did not differ between the 2 arms. CONCLUSIONS AND RELEVANCE: We did not find noninferiority of β-lactam monotherapy in patients hospitalized for moderately severe community-acquired pneumonia. Patients infected with atypical pathogens or with PSI category IV pneumonia had delayed clinical stability with monotherapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00818610.

Influence of noninjecting and injecting drug use on mortality, retention in the cohort, and antiretroviral therapy, in participants in the Swiss HIV Cohort Study.

OBJECTIVES: We studied the influence of noninjecting and injecting drug use on mortality, dropout rate, and the course of antiretroviral therapy (ART), in the Swiss HIV Cohort Study (SHCS). METHODS: Cohort participants, registered prior to April 2007 and with at least one drug use questionnaire completed until May 2013, were categorized according to their self-reported drug use behaviour. The probabilities of death and dropout were separately analysed using multivariable competing risks proportional hazards regression models with mutual correction for the other endpoint. Furthermore, we describe the influence of drug use on the course of ART. RESULTS: A total of 6529 participants (including 31% women) were followed during 31 215 person-years; 5.1% participants died; 10.5% were lost to follow-up. Among persons with homosexual or heterosexual HIV transmission, noninjecting drug use was associated with higher all-cause mortality [subhazard rate (SHR) 1.73; 95% confidence interval (CI) 1.07-2.83], compared with no drug use. Also, mortality was increased among former injecting drug users (IDUs) who reported noninjecting drug use (SHR 2.34; 95% CI 1.49-3.69). Noninjecting drug use was associated with higher dropout rates. The mean proportion of time with suppressed viral replication was 82.2% in all participants, irrespective of ART status, and 91.2% in those on ART. Drug use lowered adherence, and increased rates of ART change and ART interruptions. Virological failure on ART was more frequent in participants who reported concomitant drug injections while on opiate substitution, and in current IDUs, but not among noninjecting drug users. CONCLUSIONS: Noninjecting drug use and injecting drug use are modifiable risks for death, and they lower retention in a cohort and complicate ART.

Estudio de bentos y sedimentología durante el Crucero Oceanográfico BIC Humboldt 9706-07

Estudia la estructura comunitaria del bentos, su variación espacio-temporal y su relación con las condiciones oceanográficas, realizando la determinación y seguimiento de los diferentes parámetros de la estructura comunitaria y su relación con la materia orgánica en el sedimiento.

Mediciones in situ de TS de diversas especies a finales del invierno de 1998. Crucero BIC Humboldt 9808-09

Se efectuaron mediciones de TS (Fuerza de Blanco, Target Strenght) durante los 108 lances de comprobación de ecotrazos realizados por el BIC Humboldt en el marco del Crucero 9808-09 de Evaluación Hidroacústica de Recursos Pelágicos. Se consideran para el análisis únicamente aquellos lances donde más del 90% de la captura perteneció a una sola especie. Los factores b20 de la ecuación de TS (TS=20 log L - b20) que han sido determinados, las cuales deberán ser considerados como provisionales, son las siguientes: Pez cinta (Trichiurus lepturus) = 70,95 (120 kHz); Vinciguerria o pez linterna (Vinciguerria lucetia pacifici) = 83,29 (120 kHz); Samasa (Anchoa nasus) = 86,57 (120 kHz); Caballa (Scomber japonicus) = 83,09 (120 kHz); Pez cinta (Trichiurus lepturus) = 71,41 (38 kHz); y Vinciguerria o pez linterna (Vinciguerria lucetia pacifici)= 82,04 (38kHz).

Estudio del ictioplancton y el zooplancton entre Puerto Pizarro y Huarmey durante el crucero de evaluación del recurso merluza BIC José Olaya Balandra 986-07

Presenta la composición, distribución, abundancia y frecuencia de las especies del ictioplancton; así mismo se hace un análisis cualitativo del zooplancton. Dentro del ictioplancton las larvas más frecuentes fueron Bremaceros bathymaster y Diogenichthys laternatus. Las que presentaron mayor abundancia fueron los huevos y larvas de Sardinops sagax sagax y Leuroglossus stilbius y las larvas de Engraulis ringens. La distribución de las larvass de merluza estuvo en la zona norte, frente a Puerto Pizarro y falso volador frente a Pimentel. Se determinó que los volúmenes del zooplancton total variaron entre 0,02 y 0,81 mL/m3. Dentro del zooplancton se registran por primera vez para el mar peruano los copépodos Augaptylus megalurus y Temeropia mayumbaensis.

Estudio del macrozoobentos durante durante el crucero de evaluación de recursos demersales BIC José Olaya Balandra 9806-07 de Puerto Pizarro a Huarmey

Estudia las muestras obtenidas en cuatro lances ubicados en el sublitoral peruano de fondo blando al norte de los 8°S frente a Puerto Pizarro, Paita, Sechura y Pimentel durante los meses de junio y julio de 1998. Los resultados obtenidos reflejan una relación directa entre las comunidades macrozoobentónicas y el recurso demersal. Se observa que las distribuciones de densidades, biomasas y diversidad son mayores en la subáreas al norte de los 6°S, teniendo como grupo más representativo a los anélidos Polychaeta.

Comportamiento de la red de arrastre de fondo tipo 450/120 empleada en el estudio de recursos demersales a inicios del invierno 1998. BIC José Olaya Balandra 9806-07 de Puerto Pizarro a Huarmey

Se determinaron correlaciones entre diferentes parámetros de funcionamiento de la red de arrastre empleadas para las calas de comprobación. Abertura vertical con Abertura horizontal, profundidad con longitud de cable, abertura vertical y abertura horizontal versus velocidad de arrastre, analizándose un total de 72 lances de comprobación. Los datos de comportamiento de la red como la abertura horizontal y abertura vertical de la boca de la red, profundidad de la red y distancia entre la relinga inferior al fondo, etc. se obtuvo en forma directa por medio del sistema SCANMAR RX 400, los arrastres tuvieron una duración promedio de 13,58 minutos con una velocidad de arrastre promedio de 3,8 nudos. Se aplicó el modelo de regresión lineal para la correlación entre los valores de: (a) abertura vertical y abertura horizontal, (b) longitud del cable de arrastre principal con la profundidad de arrastre, (c) abertura horizontal-vertical y la velocidad de arrastre.

Sedimentos marinos superficiales en la bahía del Callao, Perú. 1997

Durante El Niño 1997, se estudiaron los sedimentos marinos superficiales de la bahía del Callao (11°50’S a 12°06’S), en 68 estaciones de muestreo situadas al interior de la bahía, incluyendo Ventanilla. Se situaron 35 estaciones complementarias entre las desembocaduras de los ríos Rímac y Chillón donde se concentran las descargas de desechos industriales, urbanos y de actividad portuaria. Se realizaron tres transectos, frente a: playa Ventanilla, al colector Comas y a Chucuito-La Punta. Frente a la playa Márquez se encuentra textura areno arcillosa y hacia el norte predomina el fango; frente a Oquendo las texturas son fango y arena arcillosa. Sedimentos de grano fino, con textura limo arcillosa y arcillo limosa existen en el fondo marino de zonas más profundas y alejadas de la costa; pero también están cerca de la costa, al sur y suroeste de la zona de operaciones portuarias, frente a Chucuito y La Punta. Texturas de arena se registraron al norte del río Chillón (La Pampilla y Ventanilla), en los alrededores del banco Camotal y frente a La Punta. En las áreas más profundas y abrigadas de la bahía, los sedimentos con granulometría muy fina presentan valores negativos de asimetría, característicos de ambientes de sedimentación. En sectores donde existen sedimentos de grano más grueso ocurren procesos de transporte (tipo y forma de ondulaciones) y erosión, apreciables en imágenes del fondo, y en el análisis de parámetros estadísticos. Los altos contenidos de materia orgánica se encuentran asociados a sedimentos de grano fino en ambientes de sedimentación principalmente, está condicionado por la tasa de aporte y origen (antrópico, marino o continental) y por las condiciones de escaso oxígeno que favorecen su preservación. Los más bajos contenidos orgánicos frente a la zona costera de Ventanilla, están asociadas a sedimentos con predominancia de fracciones de arena y origen terrígeno y mayor oxigenación.

Estructura del subsistema demersal durante el verano 2004.Crucero BIC Olaya 0401-02.

El Crucero BIC Olaya 0401-02 se efectuó del 14 enero al 7 febrero 2004, de Puerto Pizarro (3°29’S) a Punta Pacasmayo (7°23’S). Se utilizó la red de arrastre Granton 300/160. Se efectuaron 87 arrastres de fondo, la captura total fue 42.015,8 kg, constituida por 169 especies: peces (102), crustáceos (32), moluscos (21), equinodermos (9), cnidarios (4) y anélidos (1). Las especies más importantes fueron: merluza peruana, Merluccius gayi peruanus (31.429,42 kg; 75% del total); bereche con barbo, Ctenosciaena peruviana (2815,67 kg; 6,7%); pota, Dosidicus gigas (1.777,27 kg; 4,2%); lenguado ojón, Hippoglossina macrops (611,82 kg; 1,5%); chiri Peprilus medius (543,67 kg; 1,3%); y el pampanito, Peprilus snyderi (497,54 kg; 1,2%). En conjunto, estas seis especies, representaron el 90% del monto total. Esta diversidad es similar al verano 2003 y también la distribución de los peces, cuya mayor diversidad específica se encontró al norte de Punta Aguja (6°S), indicando condiciones de normalidad.

Fluoroscopic-Guided Radial Endobronchial Ultrasound Without Guide Sheath For Peripheral Pulmonary Lesions: A Safe And Efficient Combination.

BACKGROUND: Several guidelines recommend computed tomography scans for populations with high-risk for lung cancer. The number of individuals evaluated for peripheral pulmonary lesions (PPL) will probably increase, and with it non-surgical biopsies. Associating a guidance method with a target confirmation technique has been shown to achieve the highest diagnostic yield, but the utility of bronchoscopy with radial probe endobronchial ultrasound using fluoroscopy as guidance without a guide sheath has not been reported. METHODS: We conducted a retrospective analysis of bronchoscopy with radial probe endobronchial ultrasound using fluoroscopy procedures for the investigation of PPL performed by experienced bronchoscopists with no specific previous training in this particular technique. Operator learning curves and radiological predictors were assessed for all consecutive patients examined during the first year of application of the technique. RESULTS: Fifty-one PPL were investigated. Diagnostic yield and visualization yield were 72.5 and 82.3% respectively. The diagnostic yield was 64.0% for PPL ≤20mm, and 80.8% for PPL>20mm. No false-positive results were recorded. The learning curve of all diagnostic tools showed a DY of 72.7% for the first sub-group of patients, 81.8% for the second, 72.7% for the third, and 81.8% for the last. CONCLUSION: Bronchoscopy with radial probe endobronchial ultrasound using fluoroscopy as guidance is safe and simple to perform, even without specific prior training, and diagnostic yield is high for PPL>and ≤20mm. Based on these findings, this method could be introduced as a first-line procedure for the investigation of PPL, particularly in centers with limited resources.

Personalized approaches to active immunotherapy in cancer

Immunotherapy is emerging as a promising anti-cancer curative modality. However, in contrast to recent advances obtained employing checkpoint blockade agents and T cell therapies, clinical efficacy of therapeutic cancer vaccines is still limited. Most vaccination attempts in the clinic represent "off-the shelf" approaches since they target common "self" tumor antigens, shared among different patients. In contrast, personalized approaches of vaccination are tailor-made for each patient and in spite being laborious, hold great potential. Recent technical advancement enabled the first steps in the clinic of personalized vaccines that target patient-specific mutated neo-antigens. Such vaccines could induce enhanced tumor-specific immune response since neo-antigens are mutation-derived antigens that can be recognized by high affinity T cells, not limited by central tolerance. Alternatively, the use of personalized vaccines based on whole autologous tumor cells, overcome the need for the identification of specific tumor antigens. Whole autologous tumor cells could be administered alone, pulsed on dendritic cells as lysate, DNA, RNA or delivered to dendritic cells in-vivo through encapsulation in nanoparticle vehicles. Such vaccines may provide a source for the full repertoire of the patient-specific tumor antigens, including its private neo-antigens. Furthermore, combining next-generation personalized vaccination with other immunotherapy modalities might be the key for achieving significant therapeutic outcome.

L'Écho de Paris

1886/07/21 (Numéro 860).

25/07/20, Tour de France, arrivée de [Jean] Rossius, gagnant de la dernière étape : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 60204