Profound Pathogen-Specific Alterations in Intestinal Microbiota Composition Precede Late-Onset Sepsis in Preterm Infants:A Longitudinal, Multicenter, Case-Control Study

BACKGROUND: The role of intestinal microbiota in the pathogenesis of late-onset sepsis (LOS) in preterm infants is largely unexplored but could provide opportunities for microbiota-targeted preventive and therapeutic strategies. We hypothesized that microbiota composition changes before the onset of sepsis, with causative bacteria that are isolated later in blood culture. METHODS: This multicenter case-control study included preterm infants born under 30 weeks of gestation. Fecal samples collected from the 5 days preceding LOS diagnosis were analyzed using a molecular microbiota detection technique. LOS cases were subdivided into 3 groups: gram-negative, gram-positive, and coagulase-negative Staphylococci (CoNS). RESULTS: Forty LOS cases and 40 matched controls were included. In gram-negative LOS, the causative pathogen could be identified in at least 1 of the fecal samples collected 3 days prior to LOS onset in all cases, whereas in all matched controls, this pathogen was absent (P = .015). The abundance of these pathogens increased from 3 days before clinical onset. In gram-negative and gram-positive LOS (except CoNS) combined, the causative pathogen could be identified in at least 1 fecal sample collected 3 days prior to LOS onset in 92% of the fecal samples, whereas these pathogens were present in 33% of the control samples (P = .004). Overall, LOS (expect CoNS) could be predicted 1 day prior to clinical onset with an area under the curve of 0.78. CONCLUSIONS: Profound preclinical microbial alterations underline that gut microbiota is involved in the pathogenesis of LOS and has the potential as an early noninvasive biomarker

Therapeutic Validity and Effectiveness of Preoperative Exercise on Functional Recovery after Joint Replacement: A Systematic Review and Meta-Analysis

Background: Our aim was to develop a rating scale to assess the therapeutic validity of therapeutic exercise programmes. By use of this rating scale we investigated the therapeutic validity of therapeutic exercise in patients awaiting primary total joint replacement (TJR). Finally, we studied the association between therapeutic validity of preoperative therapeutic exercise and its effectiveness in terms of postoperative functional recovery. Methods: (Quasi) randomised clinical trials on preoperative therapeutic exercise in adults awaiting TJR on postoperative recovery of functioning within three months after surgery were identified through database and reference screening. Two reviewers extracted data and assessed the risk of bias and therapeutic validity. Therapeutic validity of the interventions was assessed with a nine-itemed, expert-based rating scale (scores range from 0 to 9; score ≥6 reflecting therapeutic validity), developed in a four-round Delphi study. Effects were pooled using a random-effects model and meta-regression was used to study the influence of therapeutic validity. Results: Of the 7,492 articles retrieved, 12 studies (737 patients) were included. None of the included studies demonstrated therapeutic validity and two demonstrated low risk of bias. Therapeutic exercise was not associated with 1) observed functional recovery during the hospital stay (Standardised Mean Difference [SMD]: −1.19; 95%-confidence interval [CI], −2.46 to 0.08); 2) observed recovery within three months of surgery (SMD: −0.15; 95%-CI, −0.42 to 0.12); and 3) self-reported recovery within three months of surgery (SMD −0.07; 95%-CI, −0.35 to 0.21) compared with control participants. Meta-regression showed no statistically significant relationship between therapeutic validity and pooled-effects. Conclusion: Preoperative therapeutic exercise for TJR did not demonstrate beneficial effects on postoperative functional recovery. However, poor therapeutic validity of the therapeutic exercise programmes may have hampered potentially beneficial effects, since none of the studies met the predetermined quality criteria. Future review studies on therapeutic exercise should address therapeutic validity. (aut.ref.

NEOnatal Central-venous Line Observational study on Thrombosis (NEOCLOT): Evaluation of a national guideline on management of neonatal catheter-related thrombosis

Background: In critically ill (preterm) neonates, central venous catheters (CVCs) are increasingly used for administration of medication or parenteral nutrition. A serious complication, however, is the development of catheter-related thrombosis (CVC-thrombosis), which may resolve by itself or cause severe complications. Due to lack of evidence, management of neonatal CVC-thrombosis varies among neonatal intensive care units (NICUs). In the Netherlands an expert-based national management guideline has been developed which is implemented in all 10 NICUs in 2014. Methods: The NEOCLOT study is a multicentre prospective observational cohort study, including 150 preterm and term infants (0-6 months) admitted to one of the 10 NICUs, developing CVC-thrombosis. Patient characteristics, thrombosis characteristics, risk factors, treatment strategies and outcome measures will be collected in a web-based database. Management of CVC-thrombosis will be performed as recommended in the protocol. Violations of the protocol will be noted. Primary outcome measures are a composite efficacy outcome consisting of death due to CVC-thrombosis and recurrent thrombosis, and a safety outcome consisting of the incidence of major bleedings during therapy. Secondary outcomes include individual components of primary efficacy outcome, clinically relevant non-major and minor bleedings and the frequency of risk factors, protocol variations, residual thrombosis and post thrombotic syndrome. Discussion: The NEOCLOT study will evaluate the efficacy and safety of the new, national, neonatal CVC-thrombosis guideline. Furthermore, risk factors as well as long-term consequences of CVC-thrombosis will be analysed

Making the elderly fit for surgery

Prehabilitation promotes rehabilitation

Relationship between lung function and Modified Shuttle Test performance in adult patients with cystic fibrosis : A cross-sectional, retrospective study

Objectives: To investigate the relationship between lung function and exercise capacity in adults with cystic fibrosis (CF), and to develop a CF-specific equation to predict Modified Shuttle Test (MST) performance from baseline data. Design: Cross-sectional, retrospective study. Setting: Adult CF centre. Participants: One hundred and twenty-seven patients with CF [61 male; mean age 25 years (range 17 to 52 years), mean forced expiratory volume in 1 second (FEV1) 56% predicted (range 15 to 124%)]. Main outcome measures: MST and FEV1. Results: Overall, a moderate-to-good relationship was found between lung function and MST performance (walking distance vs FEV1% predicted: r = 0.64, P = 0.01). This relationship between FEV1 and MST shows an obvious threshold at an FEV1 of 67% predicted. Above this threshold, no significant association was observed between FEV1 and MST performance. However, a strong relationship (MST vs FEV1% predicted: r ≥ 0.74, P <0.01 for men and r = 0.79, P <0.01 for women) was found below an FEV1 of 67% predicted. Conclusions: This study suggests that a strong association exists between lung function (FEV1% predicted) and MST (walking distance) in adult patients with moderate-to-severe CF (FEV1 <67% predicted). A reference equation for MST performance was developed for those patients with FEV1 ≤67% predicted, providing a tool to make an a-priori prediction of MST walking distance

Usefulness of the bilirubin/albumin ratio for predicting bilirubin-induced neurotoxicity in premature infants

Unconjugated hyperbilirubinaemia occurs in almost all premature infants and is potentially neurotoxic. Treatment is based on total serum bilirubin (TSB), but treatment thresholds are not evidence based. Free bilirubin (Bf) - that is, not bound to albumin, seems a better parameter for bilirubin neurotoxicity, but measurements of Bf are not available in clinical practice. The bilirubin/albumin (B/A) ratio is considered a surrogate parameter for Bf and an interesting additional parameter in the management of hyperbilirubinaemia. This paper reviewed the evidence supporting the use of B/A ratios for predicting bilirubin-induced neurological dysfunction (BIND) including neurodevelopmental delay in jaundiced premature infants (gestational age less than 32 weeks). A literature search was performed and six publications reviewed regarding B/A ratios in the management and outcome of jaundiced premature infants. No prospective clinical trials had been undertaken to show whether bilirubin-induced neurotoxicity is reduced or whether unnecessary treatment is avoided by using the B/A ratio in addition to TSB. Recently, a randomised controlled trial evaluating the effect of the additional use of the B/A ratio on neurodevelopmental outcome in jaundiced premature infants has been initiated. Based on the prevailing evidence many authorities suggest that the additional use of the B/A ratio may be valuable when evaluating jaundiced premature infants

Feasibility and preliminary effectiveness of preoperative therapeutic exercise in patients with cancer:a pragmatic study

The aim of this pilot study is to determine the feasibility and preliminary effectiveness of an individually designed preoperative therapeutic exercise program (PreTEP), in patients recently diagnosed with cancer and awaiting elective surgery. The purpose is to improve their physical fitness levels during this waiting period with the intention of decreasing postoperative morbidity. A preexperimental pilot study was performed at the University Medical Center Utrecht, The Netherlands. Thirty-nine patients diagnosed with cancer, scheduled for elective abdominal/thoracic surgery, were referred to a multidisciplinary preoperative screening. Fifteen patients (38%) participated in PreTEP. Participants were satisfied and motivated during the period of training (on average 5 weeks) in which they attended 84% of the sessions. Cardiorespiratory fitness (A strand-test) and muscle strength (Handheld Dynamometry) increased significantly, from 25 to 33 mL/kg/min, respectively (p<0.01; 95% confidence interval [CI]=-0.011 to -0.004) and from 894 Newton (N) to 961N (p<0.01; 95% CI=-94.53 to -39.0). No adverse events occurred during the training period. PreTEP was shown to be feasible, safe, and well-tolerated and appreciated by participants. Despite the relatively short period of training, physical fitness improved in all participants