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Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. National Institute for Health Research Health Services and Delivery Research Programme.

We previously reported outcome-associated decreases in muscle energetic status and mitochondrial dysfunction in septic patients with multiorgan failure. We postulate that survivors have a greater ability to maintain or recover normal mitochondrial functionality. To determine whether mitochondrial biogenesis, the process promoting mitochondrial capacity, is affected in critically ill patients. Muscle biopsies were taken from 16 critically ill patients recently admitted to intensive care (average 1-2 d) and from 10 healthy, age-matched patients undergoing elective hip surgery. Survival, mitochondrial morphology, mitochondrial protein content and enzyme activity, mitochondrial biogenesis factor mRNA, microarray analysis, and phosphorylated (energy) metabolites were determined. Ten of 16 critically ill patients survived intensive care. Mitochondrial size increased with worsening outcome, suggestive of swelling. Respiratory protein subunits and transcripts were depleted in critically ill patients and to a greater extent in nonsurvivors. The mRNA content of peroxisome proliferator-activated receptor γ coactivator 1-α (transcriptional coactivator of mitochondrial biogenesis) was only elevated in survivors, as was the mitochondrial oxidative stress protein manganese superoxide dismutase. Eventual survivors demonstrated elevated muscle ATP and a decreased phosphocreatine/ATP ratio. Eventual survivors responded early to critical illness with mitochondrial biogenesis and antioxidant defense responses. These responses may partially counteract mitochondrial protein depletion, helping to maintain functionality and energetic status. Impaired responses, as suggested in nonsurvivors, could increase susceptibility to mitochondrial damage and cellular energetic failure or impede the ability to recover normal function. Clinical trial registered with clinical trials.gov (NCT00187824).

Background and objectivesA clinical trial in 93 National Health Service hospitals evaluated a quality improvement programme for emergency abdominal surgery, designed to improve mortality by improving the patient care pathway. Large variation was observed in implementation approaches, and the main trial result showed no mortality reduction. Our objective therefore was to evaluate whether trial participation led to care pathway implementation and to study the relationship between care pathway implementation and use of six recommended implementation strategies.MethodsWe performed a hospital-level time-series analysis using data from the Enhanced Peri-Operative Care for High-risk patients trial. Care pathway implementation was defined as achievement of >80% median reliability in 10 measured care processes. Mean monthly process performance was plotted on run charts. Process improvement was defined as an observed run chart signal, using probability-based ‘shift’ and ‘runs’ rules. A new median performance level was calculated after an observed signal.ResultsOf 93 participating hospitals, 80 provided sufficient data for analysis, generating 800 process measure charts from 20 305 patient admissions over 27 months. No hospital reliably implemented all 10 processes. Overall, only 279 of the 800 processes were improved (3 (2–5) per hospital) and 14/80 hospitals improved more than six processes. Mortality risk documented (57/80 (71%)), lactate measurement (42/80 (53%)) and cardiac output guided fluid therapy (32/80 (40%)) were most frequently improved. Consultant-led decision making (14/80 (18%)), consultant review before surgery (17/80 (21%)) and time to surgery (14/80 (18%)) were least frequently improved. In hospitals using ≥5 implementation strategies, 9/30 (30%) hospitals improved ≥6 care processes compared with 0/11 hospitals using ≤2 implementation strategies.ConclusionOnly a small number of hospitals improved more than half of the measured care processes, more often when at least five of six implementation strategies were used. In a longer term project, this understanding may have allowed us to adapt the intervention to be effective in more hospitals.

OBJECTIVE: To evaluate the accuracy of a preliminary diagnosis based solely on patient history and physical examination in medical outpatients with abdominal or chest pain. DESIGN: Prospective observational study. SETTING: General medical outpatient clinic in a university teaching hospital. PARTICIPANTS: One hundred ninety new, consecutive patients with a mean age of 44 years (SD = 14 years, range 30–58 years) with a main complaint of abdominal or chest pain. MEASUREMENTS AND MAIN RESULTS: The preliminary diagnosis, established on the basis of patient history and physical examination, was compared with a final diagnosis, obtained after workup at completion of the chart. A nonorganic cause was established in 66 (59%) of 112 patients with abdominal pain and in 65 (83%) of 78 with chest pain. The preliminary diagnosis of “nonorganic” versus “organic” causes was correct in 79% of patients with abdominal pain and in 88% of patients with chest pain. An “undoubted” preliminary diagnosis predicted a correct assessment in all patients with abdominal pain and in all but one patient with chest pain. Overall, only 4 patients (3%) were initially incorrectly diagnosed as having a nonorganic cause of pain rather than an organic cause. In addition, final nonorganic diagnosis (n= 131) was compared with long‐term follow‐up by obtaining information from patients and, if necessary, from treating physicians. Follow‐up information, obtained for 71% of these patients after a mean of 29 months (range 18–56 months) identified three other patients that had been misdiagnosed as having abdominal pain of nonorganic causes. Compared with follow‐up, the diagnostic accuracy for nonorganic abdominal and chest pain at chart completion was 93% and 98%, respectively. CONCLUSIONS: A preliminary diagnosis of nonorganic versus organic abdominal or chest pain based on patient history and physical examination proved remarkably reliable. Accuracy was almost complete in patients with an “undoubted” preliminary diagnosis, suggesting that watchful waiting can be recommended in such cases. KEY WORDS: abdominal pain; chest pain; outpatients; nonorganic diagnosis; patient history.

This report details the case of a 67-year-old man who required intubation following a fall and multiple rib fractures and underwent surgical tracheostomy. Postoperatively, he deteriorated on the intensive care unit with airway obstruction. Bronchoscopy demonstrated tracheostomy cuff herniation obstructing airflow necessitating conventional orotracheal reintubation. On inspection of the tracheostomy an unusual cuff deformation was noted.

This report details the case of a 67-year-old man who required intubation following a fall and multiple rib fractures and underwent surgical tracheostomy. Postoperatively, he deteriorated on the intensive care unit with airway obstruction. Bronchoscopy demonstrated tracheostomy cuff herniation obstructing airflow necessitating conventional orotracheal reintubation. On inspection of the tracheostomy an unusual cuff deformation was noted.

Different peroxidases, including 2-cysteine (2-Cys) peroxiredoxins (PRXs) and thylakoid ascorbate peroxidase (tAPX), have been proposed to be involved in the water-water cycle (WWC) and hydrogen peroxide (H2O2)-mediated signaling in plastids. We generated an Arabidopsis (Arabidopsis thaliana) double-mutant line deficient in the two plastid 2-Cys PRXs (2-Cys PRX A and B, 2cpa 2cpb) and a triple mutant deficient in 2-Cys PRXs and tAPX (2cpa 2cpb tapx). In contrast to wild-type and tapx single-knockout plants, 2cpa 2cpb double-knockout plants showed an impairment of photosynthetic efficiency and became photobleached under high light (HL) growth conditions. In addition, double-mutant plants also generated elevated levels of superoxide anion radicals, H2O2, and carbonylated proteins but lacked anthocyanin accumulation under HL stress conditions. Under HL conditions, 2-Cys PRXs seem to be essential in maintaining the WWC, whereas tAPX is dispensable. By comparison, this HL-sensitive phenotype was more severe in 2cpa 2cpb tapx triple-mutant plants, indicating that tAPX partially compensates for the loss of functional 2-Cys PRXs by mutation or inactivation by overoxidation. In response to HL, H2O2- and photooxidative stress-responsive marker genes were found to be dramatically up-regulated in 2cpa 2cpb tapx but not 2cpa 2cpb mutant plants, suggesting that HL-induced plastid to nucleus retrograde photooxidative stress signaling takes place after loss or inactivation of the WWC enzymes 2-Cys PRX A, 2-Cys PRX B, and tAPX.

Reactive electrophile species (RES), including prostaglandins, phytoprostanes and 12-oxo phytodienoic acid (OPDA), activate detoxification responses in plants and animals. However, the pathways leading to the activation of defense reactions related to abiotic or biotic stress as a function of RES formation, accumulation or treatment are poorly understood in plants. Here, the thiol-modification of proteins, including the RES-activated basic region/leucine zipper transcription factor TGA2, was studied. TGA2 contains a single cysteine residue (Cys186) that was covalently modified by reactive cyclopentenones but not required for induction of detoxification genes in response to OPDA or prostaglandin A1. Activation of the glutathione-S-transferase 6 (GST6) promoter was responsive to cyclopentenones but not to unreactive cyclopentanones, including jasmonic acid suggesting that thiol reactivity of RES is important to activate the TGA2-dependent signaling pathway resulting in GST6 activation We show that RES modify thiols in numerous proteins in vivo, however, thiol reactivity alone appears not to be sufficient for biological activity as demonstrated by the failure of several membrane permeable thiol reactive reagents to activate the GST6 promoter.

Continuous-flow biocatalysis utilizing immobilized enzymes emerged as a sustainable route for chemical synthesis. However, inadequate biocatalytic efficiency from current flow reactors, caused by non-productive enzyme immobilization or enzyme-carrier mismatches in size, hampers its widespread application. Here, we demonstrate a general-applicable and robust approach for the fabrication of a high-performance enzymatic continuous-flow reactor via integrating well-designed scalable isoporous block copolymer (BCP) membranes as carriers with an oriented and productive immobilization employing material binding peptides (MBP). Densely packed uniform enzyme-matched nanochannels of well-designed BCP membranes endow the desired nanoconfined environments towards a productive immobilized phytase. Tuning nanochannel properties can further regulate the complex reaction process and fortify the catalytic performance. The synergistic design of enzyme-matched carriers and efficient enzyme immobilization empowers an excellent catalytic performance with >1 month operational stability, superior productivity, and a high space-time yield (1.05 × 10 5  g L −1 d −1 ) via a single-pass continuous-flow process. The obtained performance makes the designed nano- and isoporous block copolymer membrane reactor highly attractive for industrial applications. Continuous-flow biocatalysis with immobilized enzymes is a sustainable route for chemical synthesis, but inadequate biocatalytic efficiency caused by non-productive enzyme immobilization or enzyme-carrier mismatches presents a challenge for its application. Here, the authors report an approach for the fabrication of a high-performance enzymatic continuous-flow reactor via integrating scalable isoporous block copolymer membranes as carriers with an oriented one-step enzyme immobilization via a genetically fused material binding peptide.

Jasmonates and phytoprostanes are oxylipins that regulate stress responses and diverse physiological and developmental processes. 12-Oxo-phytodienoic acid (OPDA) and phytoprostanes are structurally related electrophilic cyclopentenones, which activate similar gene expression profiles that are for the most part different from the action of the cyclopentanone jasmonic acid (JA) and its biologically active amino acid conjugates. Whereas JA–isoleucine signals through binding to COI1, the bZIP transcription factors TGA2, TGA5, and TGA6 are involved in regulation of gene expression in response to phytoprostanes. Here root growth inhibition and target gene expression were compared after treatment with JA, OPDA, or phytoprostanes in mutants of the COI1/MYC2 pathway and in different TGA factor mutants. Inhibition of root growth by phytoprostanes was dependent on COI1 but independent of jasmonate biosynthesis. In contrast, phytoprostane-responsive gene expression was strongly dependent on TGA2, TGA5, and TGA6, but not dependent on COI1, MYC2, TGA1, and TGA4. Different mutant and overexpressing lines were used to determine individual contributions of TGA factors to cyclopentenone-responsive gene expression. Whereas OPDA-induced expression of the cytochrome P450 gene CYP81D11 was primarily regulated by TGA2 and TGA5, the glutathione S-transferase gene GST25 and the OPDA reductase gene OPR1 were regulated by TGA5 and TGA6, but less so by TGA2. These results support the model that phytoprostanes and OPDA regulate differently (i) growth responses, which are COI1 dependent but jasmonate independent; and (ii) lipid stress responses, which are strongly dependent on TGA2, TGA5, and TGA6. Identification of molecular components in cyclopentenone signalling provides an insight into novel oxylipin signal transduction pathways.