Clinical risk scores and blood biomarkers as predictors of long-term outcome in patients with community-acquired pneumonia: a 6-year prospective follow-up study.

OBJECTIVE: Prediction of long-term outcomes in patients with community-acquired pneumonia (CAP) is incompletely understood. We investigated the value of clinical risk scores [pneumonia severity index (PSI) and CURB-65] (Confusion, Urea, Respiratory rate, Blood Pressure, Age >65 years) and blood biomarkers of different physiopathological pathways in predicting long-term survival in a well-characterized cohort of patients with CAP enrolled in an antibiotic stewardship trial. DESIGN, SETTING AND SUBJECTS: Patients admitted with CAP to six medical centres in Switzerland were prospectively followed for 6 years. Cox regression models and area under the receiver operating characteristics curve (AUC) were used to investigate associations between initial risk assessment and all-cause mortality. MAIN OUTCOME MEASURE: All-cause mortality during a 6-year follow-up period. RESULTS: Six-year mortality in the present cohort (median age 73 years) was 45.1% [95% confidence interval (CI) 41.8-48.3%]. Initial PSI and CURB-65 scores both had excellent long-term prognostic accuracy, with a stepwise increase in mortality per risk class. The hazard ratios (95% CI) of the highest PSI and CURB-65 classes (reference: lowest class) were 38.0 (14.0-103.0) and 7.8 (2.2-14.5), respectively, after 6 years. The addition of inflammatory (pro-adrenomedullin) and cardiac (pro-atrial natriuretic peptide) blood biomarkers measured upon hospital admission further improved the prognostic capabilities of the PSI (AUC increase from 0.79 to 0.83; P < 0.0001) and the CURB-65 score (AUC increase from 0.73 to 0.80; P < 0.001). CONCLUSION: Risk assessment using clinical scores allowed accurate long-term prognostication, which was further improved by the addition of two inflammatory (pro-adrenomedullin) and cardiac (pro-atrial natriuretic peptide) blood biomarkers. These data provide a rationale for a more risk-adapted, 'personalized' strategy for long-term management of patients with CAP.

Ultrastructural aspects of oocyte growth in the marsupial Monodelphis domestica (grey short-tailed opossum).

The growth of the opossum Monodelphis oocyte does not correspond to the strict biphasic pattern so far described in eutherians and marsupials. The oocyte increases appreciably in size during the last stage of antral follicle development. During the primordial and primary follicle stage Balbiani bodies or paranuclear complexes are not detectable in Monodelphis oocytes. Organelles are randomly distributed. In addition to the nucleolus, perichromatin and ribonucleoprotein particles are other intranuclear structures which occur as regular components in the early Monodelphis oocyte. Clusters of particles are mostly seen in close association with the nuclear envelope. Similar material has been encountered in the cytoplasm as a type of freely-existing 'nuage' material but never as mitochondria-associated 'nuage' or 'cement'. Both types of particles, intranuclear and cytoplasmic, disappear by the time antral follicle formation begins. Mitochondria are at first of the typical transformed shape seen in most mammalian oocytes. They are large, round or oval in outline with a few, often arched, cristae and a light matrix. During the primary follicle stage, mitochondrial size and complexity decrease and the matrix becomes electron dense. A close relationship between mitochondria and endoplasmic reticulum appears early in the primordial and later in the primary follicle oocyte. Regularly detected structures in the ooplasm of preantrum oocytes are paired or 'confronting' cisternae of endoplasmic reticulum, which are lamellar complexes comprised of 2 or more parallel cisternae with intervening electron-dense material. The most conspicuous inclusions in the Monodelphis oocytes of the tertiary and graafian follicles are vesicles. All other organelles are confined to the peripheral zone of the oocyte. Golgi and endoplasmic vesicles both take part in the formation of multivesicular bodies which seems to be the starting point for the vesicle accumulation. Further increase in size involves the incorporation of endocytotic vesicles and the coalescence of larger vesicles. Ordinary fixation procedure leave the vesicles empty. Cortical granules are found only in small numbers.