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PurposeTo describe data on epidemiology, microbiology, clinical characteristics and outcome of adult patients admitted in the intensive care unit (ICU) with secondary peritonitis, with special emphasis on antimicrobial therapy and source control.MethodsPost hoc analysis of a multicenter observational study (Abdominal Sepsis Study, AbSeS) including 2621 adult ICU patients with intra‐abdominal infection in 306 ICUs from 42 countries. Time-till-source control intervention was calculated as from time of diagnosis and classified into ‘emergency’ (< 2 h), ‘urgent’ (2–6 h), and ‘delayed’ (> 6 h). Relationships were assessed by logistic regression analysis and reported as odds ratios (OR) and 95% confidence interval (CI).ResultsThe cohort included 1077 cases of microbiologically confirmed secondary peritonitis. Mortality was 29.7%. The rate of appropriate empiric therapy showed no difference between survivors and non-survivors (66.4% vs. 61.3%, p = 0.1). A stepwise increase in mortality was observed with increasing Sequential Organ Failure Assessment (SOFA) scores (19.6% for a value ≤ 4–55.4% for a value > 12, p < 0.001). The highest odds of death were associated with septic shock (OR 3.08 [1.42–7.00]), late-onset hospital-acquired peritonitis (OR 1.71 [1.16–2.52]) and failed source control evidenced by persistent inflammation at day 7 (OR 5.71 [3.99–8.18]). Compared with ‘emergency’ source control intervention (< 2 h of diagnosis), ‘urgent’ source control was the only modifiable covariate associated with lower odds of mortality (OR 0.50 [0.34–0.73]).Conclusion‘Urgent’ and successful source control was associated with improved odds of survival. Appropriateness of empirical antimicrobial treatment did not significantly affect survival suggesting that source control is more determinative for outcome.

Severe intra-abdominal infection commonly requires intensive care. Mortality is high and is mainly determined by disease-specific characteristics, i.e. setting of infection onset, anatomical barrier disruption, and severity of disease expression. Recent observations revealed that antimicrobial resistance appears equally common in community-acquired and late-onset hospital-acquired infection. This challenges basic principles in anti-infective therapy guidelines, including the paradigm that pathogens involved in community-acquired infection are covered by standard empiric antimicrobial regimens, and second, the concept of nosocomial acquisition as the main driver for resistance involvement. In this study, we report on resistance profiles of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis and Enterococcus faecium in distinct European geographic regions based on an observational cohort study on intra-abdominal infections in intensive care unit (ICU) patients. Resistance against aminopenicillins, fluoroquinolones, and third-generation cephalosporins in E. coli, K. pneumoniae and P. aeruginosa is problematic, as is carbapenem-resistance in the latter pathogen. For E. coli and K. pneumoniae , resistance is mainly an issue in Central Europe, Eastern and South-East Europe, and Southern Europe, while resistance in P. aeruginosa is additionally problematic in Western Europe. Vancomycin-resistance in E. faecalis is of lesser concern but requires vigilance in E. faecium in Central and Eastern and South-East Europe. In the subcohort of patients with secondary peritonitis presenting with either sepsis or septic shock, the appropriateness of empiric antimicrobial therapy was not associated with mortality. In contrast, failure of source control was strongly associated with mortality. The relevance of these new insights for future recommendations regarding empiric antimicrobial therapy in intra-abdominal infections is discussed.

Impaired cardiac vagal function, quantified preoperatively as slower heart rate recovery (HRR) after exercise, is independently associated with perioperative myocardial injury. Parasympathetic (vagal) dysfunction may also promote (extra-cardiac) multi-organ dysfunction, although perioperative data are lacking. Assuming that cardiac vagal activity, and therefore heart rate recovery response, is a marker of brainstem parasympathetic dysfunction, we hypothesized that impaired HRR would be associated with a higher incidence of morbidity after noncardiac surgery. In two prospective, blinded, observational cohort studies, we established the definition of impaired vagal function in terms of the HRR threshold that is associated with perioperative myocardial injury (HRR ≤ 12 beats min-1 (bpm), 60 seconds after cessation of cardiopulmonary exercise testing. The primary outcome of this secondary analysis was all-cause morbidity three and five days after surgery, defined using the Post-Operative Morbidity Survey. Secondary outcomes of this analysis were type of morbidity and time to become morbidity-free. Logistic regression and Cox regression tested for the association between HRR and morbidity. Results are presented as odds/hazard ratios [OR or HR; (95% confidence intervals). 882/1941 (45.4%) patients had HRR≤12bpm. All-cause morbidity within 5 days of surgery was more common in 585/822 (71.2%) patients with HRR≤12bpm, compared to 718/1119 (64.2%) patients with HRR>12bpm (OR:1.38 (1.14-1.67); p = 0.001). HRR≤12bpm was associated with more frequent episodes of pulmonary (OR:1.31 (1.05-1.62);p = 0.02)), infective (OR:1.38 (1.10-1.72); p = 0.006), renal (OR:1.91 (1.30-2.79); p = 0.02)), cardiovascular (OR:1.39 (1.15-1.69); p<0.001)), neurological (OR:1.73 (1.11-2.70); p = 0.02)) and pain morbidity (OR:1.38 (1.14-1.68); p = 0.001) within 5 days of surgery. Multi-organ dysfunction is more common in surgical patients with cardiac vagal dysfunction, defined as HRR ≤ 12 bpm after preoperative cardiopulmonary exercise testing. ISRCTN88456378.

Between November 1998 and December 2000, the Centers for Disease Control and Prevention screened samples from 263 outbreaks of gastroenteritis in the United States and identified 3 that were associated with rotavirus among adults. Rotaviruses from each outbreak were further characterized by reverse-transcription polymerase chain reaction. Surprisingly, all specimens were of serotype G2, a strain that is, as determined by high-stringency hybridization analysis, genetically distinct in all 11 gene segments from the other common rotavirus strains in circulation. The unusual coincidence of identification of only G2 strains in these 3 outbreaks of rotavirus gastroenteritis among adults is similar to results from other studies, in which G2 strains were found in association with more-severe disease in children than other rotavirus serotypes and in association with outbreaks of diarrhea among adults in Japan. Although rotavirus infections in adults are relatively uncommon, which indicates that good overall protective immunity exists, the predominance of G2 strains in outbreaks that have occurred in adults suggests that natural immunity to more common strains does not always provide adequate heterotypic immunity to G2 strains. For the rotavirus vaccines under development, special attention may need to be paid to protection against G2 strains.

We consider join congruence relations on geometric lattices from three different points of view. First, recognizing that every matroid has an associated geometric lattice, we consider matroid operations and give conditions for when it is possible to perform the operation at the lattice level using join congruence relations. Second, we consider rank-decreasing join congruence relations. We show that a rank-decreasing join congruence relation always yields a geometric lattice. Third, we consider join congruence relations that identify a collection of points and give conditions for the resulting lattice to be geometric.

To sustain or repair cooperation during a social exchange, adaptive creatures must understand social gestures and the consequences when shared expectations about fair exchange are violated by accident or intent. We recruited 55 individuals afflicted with borderline personality disorder (BPD) to play a multiround economic exchange game with healthy partners. Behaviorally, individuals with BPD showed a profound incapacity to maintain cooperation, and were impaired in their ability to repair broken cooperation on the basis of a quantitative measure of coaxing. Neurally, activity in the anterior insula, a region known to respond to norm violations across affective, interoceptive, economic, and social dimensions, strongly differentiated healthy participants from individuals with BPD. Healthy subjects showed a strong linear relation between anterior insula response and both magnitude of monetary offer received from their partner (input) and the amount of money repaid to their partner (output). In stark contrast, activity in the anterior insula of BPD participants was related only to the magnitude of repayment sent back to their partner (output), not to the magnitude of offers received (input). These neural and behavioral data suggest that norms used in perception of social gestures are pathologically perturbed or missing altogether among individuals with BPD. This game-theoretic approach to psychopathology may open doors to new ways of characterizing and studying a range of mental illnesses.

Following peripheral axon injury, dysregulation of non-coding microRNAs (miRs) occurs in dorsal root ganglia (DRG) sensory neurons. Here we show that DRG neuron cell bodies release extracellular vesicles, including exosomes containing miRs, upon activity. We demonstrate that miR-21-5p is released in the exosomal fraction of cultured DRG following capsaicin activation of TRPV1 receptors. Pure sensory neuron-derived exosomes released by capsaicin are readily phagocytosed by macrophages in which an increase in miR-21-5p expression promotes a pro-inflammatory phenotype. After nerve injury in mice, miR-21-5p is upregulated in DRG neurons and both intrathecal delivery of a miR-21-5p antagomir and conditional deletion of miR-21 in sensory neurons reduce neuropathic hypersensitivity as well as the extent of inflammatory macrophage recruitment in the DRG. We suggest that upregulation and release of miR-21 contribute to sensory neuron–macrophage communication after damage to the peripheral nerve. Exosomes are known to contain microRNAs (miRs). Here the authors show that dorsal root ganglion neurons release exosomes containing miR-21-5p, which contributes to inflammatory cell recruitment following peripheral nerve injury.

Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which may lead to the development of rhesus disease models. Through phenotyping of macaques carrying a pathogenic OPA1:p.A8S variant, we identify a genetic model of autosomal dominant optic atrophy. Finally, we present a public website housing variant and genotype data from over two thousand rhesus macaques. This study on the genetic diversity of 1,845 rhesus macaques improves genetic variation interpretation and identifies macaque models for inherited human retinal and neurodevelopment diseases.

Background The Patient Safety Huddle (PSH) is a brief multidisciplinary daily meeting held to discuss threats to patient safety and actions to mitigate risk. Despite growing interest and application of huddles as a mechanism for improving safety, evidence of their impact remains limited. There is also variation in how huddles are conceived and implemented with insufficient focus on their fidelity (the extent to which delivered as planned) and potential ways in which they might influence outcomes. The Huddle Up for Safer Healthcare (HUSH) project attempted to scale up the implementation of patient safety huddles (PSHs) in five hospitals – 92 wards - across three UK NHS Trusts. This paper aims to assess their fidelity, time to embed, and impact on teamwork and safety culture. Methods A multi-method Developmental Evaluation was conducted. The Stages of Implementation Checklist (SIC) was used to determine time taken to embed PSHs. Observations were used to check embedded status and fidelity of PSH. A Teamwork and Safety Climate survey (TSC) was administered at two time-points: pre- and post-embedding. Changes in TSC scores were calculated for Trusts, job role and clinical speciality. Results Observations confirmed PSHs were embedded in 64 wards. Mean fidelity score was 4.9/9. PSHs frequently demonstrated a ‘fear free’ space while Statistical Process Control charts and historical harms were routinely omitted. Analysis showed a positive change for the majority (26/27) of TSC questions and the overall safety grade of the ward. Conclusions PSHs are feasible and effective for improving teamwork and safety culture, especially for nurses. PSH fidelity criteria may need adjusting to include factors deemed most useful by frontline staff. Future work should examine inter-disciplinary and role-based differences in TSC outcomes.

Continuous electronic fetal heart-rate monitoring is widely used during labour, and computerised interpretation could increase its usefulness. We aimed to establish whether the addition of decision-support software to assist in the interpretation of cardiotocographs affected the number of poor neonatal outcomes. In this unmasked randomised controlled trial, we recruited women in labour aged 16 years or older having continuous electronic fetal monitoring, with a singleton or twin pregnancy, and at 35 weeks' gestation or more at 24 maternity units in the UK and Ireland. They were randomly assigned (1:1) to decision support with the INFANT system or no decision support via a computer-generated stratified block randomisation schedule. The primary outcomes were poor neonatal outcome (intrapartum stillbirth or early neonatal death excluding lethal congenital anomalies, or neonatal encephalopathy, admission to the neonatal unit within 24 h for ≥48 h with evidence of feeding difficulties, respiratory illness, or encephalopathy with evidence of compromise at birth), and developmental assessment at age 2 years in a subset of surviving children. Analyses were done by intention to treat. This trial is completed and is registered with the ISRCTN Registry, number 98680152. Between Jan 6, 2010, and Aug 31, 2013, 47 062 women were randomly assigned (23 515 in the decision-support group and 23 547 in the no-decision-support group) and 46 042 were analysed (22 987 in the decision-support group and 23 055 in the no-decision-support group). We noted no difference in the incidence of poor neonatal outcome between the groups—172 (0·7%) babies in the decision-support group compared with 171 (0·7%) babies in the no-decision-support group (adjusted risk ratio 1·01, 95% CI 0·82–1·25). At 2 years, no significant differences were noted in terms of developmental assessment. Use of computerised interpretation of cardiotocographs in women who have continuous electronic fetal monitoring in labour does not improve clinical outcomes for mothers or babies. National Institute for Health Research.