Clinical predictors, biomarkers and pathogen discovery sequencing in suspected central nervous system infections

Central nervous system (CNS) infections are associated with high morbidity and mortality, depending on the causative pathogen. Virtually all pathogens can infect the brain or meninges surrounding it, including viruses, bacteria, fungi and parasites. The differential diagnosis in patients suspected of CNS infections is broad, and the diagnosis can be difficult to establish. Also, in a substantial part of the patients in which the diagnosis of a CNS infection is extremely likely, no pathogen can be identified by currently available diagnostic methods. Treatment and prognosis of patients with CNS infections do, however, depend on the type of CNS infection. Also, empirical treatment without confirmation of the pathogen has its drawbacks, like antimicrobial resistance or kidney damage caused by acyclovir. For this reason, development and improvement of diagnostic methods to diagnose CNS infections is needed to improve prognosis in these patients. The aim of this thesis was to assess and improve diagnostic accuracy of clinical predictors, biomarkers and pathogen discovery sequencing techniques to diagnose CNS infections. To address this aim, several methods were studied or validated in patients included in the PACEM and/or IPACE studies, which included consecutive patients in whom a lumbar puncture was performed because of the suspicion of a CNS infection

Clinical predictors, biomarkers and pathogen discovery sequencing in suspected central nervous system infections

Central nervous system (CNS) infections are associated with high morbidity and mortality, depending on the causative pathogen. Virtually all pathogens can infect the brain or meninges surrounding it, including viruses, bacteria, fungi and parasites. The differential diagnosis in patients suspected of CNS infections is broad, and the diagnosis can be difficult to establish. Also, in a substantial part of the patients in which the diagnosis of a CNS infection is extremely likely, no pathogen can be identified by currently available diagnostic methods. Treatment and prognosis of patients with CNS infections do, however, depend on the type of CNS infection. Also, empirical treatment without confirmation of the pathogen has its drawbacks, like antimicrobial resistance or kidney damage caused by acyclovir. For this reason, development and improvement of diagnostic methods to diagnose CNS infections is needed to improve prognosis in these patients. The aim of this thesis was to assess and improve diagnostic accuracy of clinical predictors, biomarkers and pathogen discovery sequencing techniques to diagnose CNS infections. To address this aim, several methods were studied or validated in patients included in the PACEM and/or IPACE studies, which included consecutive patients in whom a lumbar puncture was performed because of the suspicion of a CNS infection

The effect of remote ischaemic preconditioning on postoperative cardiac and inflammatory biomarkers in pancreatic surgery: a randomized controlled trial

Background: Cardiac and inflammatory biomarkers have been associated with adverse outcome after major abdominal surgery. This study investigated the effect of remote ischaemic preconditioning (RIPC) on perioperative concentrations of high-sensitive cardiac troponin (hs-cTn) T and interleukin (IL) 6. Methods: Adult patients scheduled for elective pancreatic surgery between March 2017 and February 2019 were randomized to either three cycles of upper-limb ischaemia and reperfusion (each 5 min) or a sham procedure before surgery. The primary endpoint was the maximum postoperative hs-cTnT concentration within 48 h after surgery. Secondary endpoints were postoperative myocardial injury (PMI), defined as an absolute increase of hs-cTnT of at least 14 ng/l above baseline concentration, maximum concentration of IL-6 within 48 h after surgery and postoperative complications within 30 days of surgery. Results: Of 99 eligible patients, 46 underwent RIPC and 46 a sham procedure. RIPC did not reduce the maximum hs-cTnT concentration after surgery (12.6 ng/l RIPC, 16.6 ng/l controls, P=0.225), nor did it lessen the incidence of PMI (15/45 RIPC, 18/45 controls, P=0.375). The maximum postoperative IL-6 concentration was 265 pg/ml after RIPC versus 385 pg/ml in controls (P=0.108). Postoperative complications occurred in 23 RIPC and 24 control patients respectively. Conclusions: Remote ischaemic preconditioning did not reduce the maximum postoperative hs-cTnT concentration. Postoperative myocardial injury, IL-6 concentrations and postoperative complications were similar between RIPC patients and controls

Radiative Transfer for Exoplanet Atmospheres

Remote sensing of the atmospheres of distant worlds motivates a firm understanding of radiative transfer. In this review, we provide a pedagogical cookbook that describes the principal ingredients needed to perform a radiative transfer calculation and predict the spectrum of an exoplanet atmosphere, including solving the radiative transfer equation, calculating opacities (and chemistry), iterating for radiative equilibrium (or not), and adapting the output of the calculations to the astronomical observations. A review of the state of the art is performed, focusing on selected milestone papers. Outstanding issues, including the need to understand aerosols or clouds and elucidating the assumptions and caveats behind inversion methods, are discussed. A checklist is provided to assist referees/reviewers in their scrutiny of works involving radiative transfer. A table summarizing the methodology employed by past studies is provided.Comment: 7 pages, no figures, 1 table. Filled in missing information in references, main text unchange

A comparison of variant theories of intact biochemical systems. II. flux-oriented and metabolic control theories

In the past two decades, several theories, all ultimately based upon the same power-law formalism, have been proposed to relate the behavior of intact biochemical system to the properties of their underlying determinants. Confusion concerning the relatedness of these alternatives has become acute because the implications of these theories have never been compared. In the preceding paper we characterized a specific system involving enzyme- enzyme interactions for reference in comparing alternative theories. We also analyzed the reference system by using an explicit variant that involves the S-system representation within biochemical systems theory (BST). We now analyze the same reference system according to two other variants within BST. First, we carry out the analysis by using an explicit variant that involves the generalized mass action representation, which includes the flux-oriented theory of Crabtee and Newsholme as a special case. Second, we carry out the analysis by using an implicit variant that involves the generalized mass action representation, which includes the metabolic control theory of Kacser and his colleagues as a special case. The explicit variants are found to provide a more complete characterization of the reference system that the implicit variants. Within each of these variant classes, the S-system representation is shown to be more mathematically tractable and accurate than the generalized mass action representation. The results allow one to make clear distinctions among the variant theories.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27910/1/0000331.pd

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700