Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock – a systematic review and meta-analysis

INTRODUCTION: Procalcitonin (PCT) algorithms for antibiotic treatment decisions have been studied in adult patients from primary care, emergency department, and intensive care unit (ICU) settings, suggesting that procalcitonin-guided therapy may reduce antibiotic exposure without increasing the mortality rate. However, information on the efficacy and safety of this approach in the most vulnerable population of critically ill patients with severe sepsis and septic shock is missing. METHOD: Two reviewers independently performed a systematic search in PubMed, Embase, ISI Web of Knowledge, BioMed Central, ScienceDirect, Cochrane Central Register of Controlled Trials, http://www.ClinicalTrials.gov and http://www.ISRCTN.org. Eligible studies had to be randomized controlled clinical trials or cohort studies which compare procalcitonin-guided therapy with standard care in severe sepsis patients and report at least one of the following outcomes: hospital mortality, 28-day mortality, duration of antimicrobial therapy, length of stay in the intensive care unit or length of hospital stay. Disagreements about inclusion of studies and judgment of bias were solved by consensus. RESULTS: Finally seven studies comprising a total of 1,075 patients with severe sepsis or septic shock were included in the meta-analysis. Both hospital mortality (RR [relative risk]: 0.91, 95%CI [confidence interval]: 0.61; 1.36) and 28-day mortality (RR: 1.02, 95%CI: 0.85; 1.23) were not different between procalcitonin-guided therapy and standard treatment groups. Duration of antimicrobial therapy was significantly reduced in favor of procalcitonin-guided therapy (HR [hazard ratio]: 1.27, 95%CI: 1.01; 1.53). Combined estimates of the length of stay in the ICU and in hospital did not differ between groups. CONCLUSION: Procalcitonin-guided therapy is a helpful approach to guide antibiotic therapy and surgical interventions without a beneficial effect on mortality. The major benefit of PCT-guided therapy consists of a shorter duration of antibiotic treatment compared to standard care. Trials are needed to investigate the effect of PCT-guided therapy on mortality, length of ICU and in-hospital stay in severe sepsis patients

Diagnostic Confidence of Run-Off CT-Angiography as the Primary Diagnostic Imaging Modality in Patients Presenting with Acute or Chronic Peripheral Arterial Disease

Objectives To investigate the reliability of CT-angiography of the lower extremities (run-off CTA) to derive a treatment decision in patients with acute and chronic peripheral artery disease (PAD). Materials and Methods 314 patients referred for run-off CTA were includ-ed in this retrospective study. First, diagnostic confidence of run-off CTA to derive a treat-ment decision was assessed in an interdisciplinary vascular conference using a 2 point scale (sufficient or not sufficient diagnostic confidence) and compared with the image quality eval-uated by two readers in consensus in four different levels (abdominopelvic, thigh, calf, foot arteries). Second, reliability of treatment decision was verified in all patients undergoing re-vascularization therapy. Results Diagnostic confidence of run-off CTA to derive a treatment deci-sion was sufficient in all patients with acute and in 97% of patients (215/221) with chronic PAD, whereas the rate of run-off CTA with non-diagnostic image quality was considerably higher in the calf and foot level (acute vs. chronic; calf: 28% vs.17%; foot: 52% vs. 20%). Reliability of treatment decision was superior for patients with chronic (123/133 = 92%) than for patients with acute PAD (64/78 = 82%, P = 0.02). Conclusion Run-off CTA is a reliable imaging modality for primary diag-nostic work-up of patients with acute and chronic PAD

Lung tumour growth kinetics in SPC-c-Raf-1-BB transgenic mice assessed by longitudinal in-vivo micro-CT quantification

<p>Abstract</p> <p>Background</p> <p>SPC-c-Raf-1-BxB transgenic mice develop genetically induced disseminated lung adenocarcinoma allowing examination of carcinogenesis and evaluation of novel treatment strategies. We report on assessment of lung tumour growth kinetics using a semiautomated region growing segmentation algorithm.</p> <p>Methods</p> <p>156 non contrast-enhanced respiratory gated micro-CT of the lungs were obtained in 12 SPC-raf transgenic (n = 9) and normal (n = 3) mice at different time points. Region-growing segmentation of the aerated lung areas was obtained as an inverse surrogate for tumour burden. Time course of segmentation volumes was assessed to demonstrate the potential of the method for follow-up studies.</p> <p>Results</p> <p>Micro-CT allowed assessment of tumour growth kinetics and semiautomated region growing enabled quantitative analysis. Significant changes of the segmented lung volumes over time could be shown (<it>p </it>= 0.009). Significant group differences could be detected between transgenic and normal animals for time points 8 to 13 months (<it>p </it>= 0.043), when marked tumour progression occurred.</p> <p>Conclusion</p> <p>The presented region-growing segmentation algorithm allows in-vivo quantification of multifocal lung adenocarcinoma in SPC-raf transgenic mice. This enables the assessment of tumour load and progress for the study of carcinogenesis and the evaluation of novel treatment strategies.</p

Stabilizing A Vascularized Autologous Matrix with Flexible Magnesium Scaffolds to Reconstruct Dysfunctional Left Ventricular Myocardium in a Large-Animal Feasibility Study

The surgical reconstruction of dysfunctional myocardium is necessary for patients with severe heart failure. Autologous biomaterials, such as vascularized patch materials, have a regenerative potential due to in vivo remodeling. However, additional temporary mechanical stabilization of the biomaterials is required to prevent aneurysms or rupture. Degradable magnesium scaffolds could prevent these life-threatening risks. A left ventricular transmural defect was reconstructed in minipigs with a piece of the autologous stomach. Geometrically adaptable and degradable scaffolds made of magnesium alloy LA63 were affixed on the epicardium to stabilize the stomach tissue. The degradation of the magnesium structures, their biocompatibility, physiological remodeling of the stomach, and the heart’s function were examined six months after the procedure via MRI (Magnetic Resonance Imaging), angiography, µ-CT, and light microscopy. All animals survived the surgery. Stable physiological integration of the stomach patch could be detected. No ruptures of the grafts occurred. The magnesium scaffolds showed good biocompatibility. Regenerative surgical approaches for treating severe heart failure are a promising therapeutic alternative to the currently available, far from optimal options. The temporary mechanical stabilization of viable, vascularized grafts facilitates their applicability in clinical scenarios

Qualitative and quantitative evaluation of computed tomography changes in adults with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor: a retrospective observational study

Introduction: The availability of highly effective triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination therapy with elexacaftor–tezacaftor–ivacaftor (ETI) has improved pulmonary outcomes and quality of life of people with cystic fibrosis (pwCF). The aim of this study was to assess computed tomography (CT) changes under ETI visually with the Brody score and quantitatively with dedicated software, and to correlate CT measures with parameters of clinical response.Methods: Twenty two adult pwCF with two consecutive CT scans before and after ETI treatment initiation were retrospectively included. CT was assessed visually employing the Brody score and quantitatively by YACTA, a well-evaluated scientific software computing airway dimensions and lung parenchyma with wall percentage (WP), wall thickness (WT), lumen area (LA), bronchiectasis index (BI), lung volume and mean lung density (MLD) as parameters. Changes in CT metrics were evaluated and the visual and quantitative parameters were correlated with each other and with clinical changes in sweat chloride concentration, spirometry [percent predicted of forced expiratory volume in one second (ppFEV1)] and body mass index (BMI).Results: The mean (SD) Brody score improved with ETI [55 (12) vs. 38 (15); p &lt; 0.001], incl. sub-scores for mucus plugging, peribronchial thickening, and parenchymal changes (all p &lt; 0.001), but not for bronchiectasis (p = 0.281). Quantitatve WP (p &lt; 0.001) and WT (p = 0.004) were reduced, conversely LA increased (p = 0.003), and BI improved (p = 0.012). Lung volume increased (p &lt; 0.001), and MLD decreased (p &lt; 0.001) through a reduction of ground glass opacity areas (p &lt; 0.001). Changes of the Brody score correlated with those of quantitative parameters, exemplarily WT with the sub-score for mucus plugging (r = 0.730, p &lt; 0.001) and peribronchial thickening (r = 0.552, p = 0.008). Changes of CT parameters correlated with those of clinical response parameters, in particular ppFEV1 with the Brody score (r = −0.606, p = 0.003) and with WT (r = −0.538, p = 0.010).Discussion: Morphological treatment response to ETI can be assessed using the Brody score as well as quantitative CT parameters. Changes in CT correlated with clinical improvements. The quantitative analysis with YACTA proved to be an objective, reproducible and simple method for monitoring lung disease, particularly with regard to future interventional clinical trials

Evaluation of CT vascularization patterns for survival prognosis in patients with hepatocellular carcinoma treated by conventional TACE

PURPOSE:Transarterial chemoembolization (TACE) is an established treatment for intermediate stage hepatocellular carcinoma (HCC). The aim of this retrospective study was to evaluate the power of lesion vascularization criteria based on computed tomography for prognosis of overall survival before initiation of treatment.METHODS:A total of 59 patients with intermediate stage HCC treated with TACE as first-line treatment were retrospectively evaluated. TACE procedures were performed using doxorubicin, cisplatin, and lipiodol. Response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) were used to determine the initial tumor response. Four vascularization patterns (VP) of the largest target lesion (homogeneous vascularization [VP1], homogeneous vascularization with additional arterial hypervascularization [VP2], heterogeneous vascularization with [VP3] and without zones of hypervascularization [VP4]) were assessed prior to the first TACE and correlated to survival.RESULTS:Kaplan-Meier analysis yielded a median overall survival of 608 days (standard error [SE], 120.5 days). Survival analysis showed significant differences depending on the vascularization patterns (P = 0.012; hazard ratio, 0.327): patients with homogeneously vascularized lesions (VP1, VP2) had a median overall survival of 1091 days (SE, 235.5 days). Patients with heterogeneous vascularization of the lesion (VP3 and VP4) showed a median overall survival of 508 days (SE, 113.9 days).CONCLUSION:The vascularization pattern of the largest HCC lesion is helpful for survival prognosis under TACE treatment and therefore has the potential to be used as an additional parameter for treatment stratification