Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.).

The six clones pTB112, pTB324, pTBs12, pCd122, pCd14 and pCd13 cover the tox locus of Clostridium difficile VPI 10463. This region of 19 kb of chromosomal DNA contains four open reading frames including the complete toxB and toxA genes. The two toxins show 63% amino acid (aa) homology, a relatedness that had been predicted by the cross-reactivity of some monoclonal antibodies (mAb) but that is in contrast to the toxin specificity of polyclonal antisera. A special feature of ToxA and ToxB is their repetitive C-termini. We define herein 19 individual CROPs (combined repetitive oligopeptides of 20-50 aa length) in the ToxB C-terminus, which are separable into five homologous groups. Comparison of the aa sequences of the N-terminal two-thirds of ToxA and ToxB revealed three marked structures, a cluster of 172 hydrophobic, highly conserved aa in the centre of both toxins, a sequence of 120 residues with an accumulation of highly conserved arginine, cysteine, histidine, methionine, and tryptophan residues, and a stretch of 248 less conserved aa. The probable function of these domains is discussed. Structural and functional homologies of ToxA and ToxB indicate that both genes have a common ancestor and may have evolved by gene duplication, with subsequent recombination and mutation, as has been reported for streptococcal glucosyltransferases (Gtf).

BackgroundRemote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham‐RIPC.Methods and ResultsIn this follow‐up paper, we present 1‐year follow‐up of the composite primary end point and its individual components (all‐cause mortality, myocardial infarction, stroke and acute renal failure), in a sub‐group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1‐year composite primary end point (RIPC versus sham‐RIPC 16.4% versus 16.9%) and its individual components (all‐cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively.ConclusionsSimilar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long‐term outcome in cardiac surgery patients undergoing propofol anesthesia.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703.

German Clinical Trials Register DRKS00003084.

BackgroundPain after surgery is a major issue for patient discomfort and often associated with delayed recovery. The aim of the present study was to evaluate the prevalence of pain and requirement for analgesics up to 6 months after elective surgery, independent if new pain symptoms occurred after surgery or if preoperative pain persisted in the postoperative period.MethodsA prospective observational single center cohort study was conducted between January 2012 and August 2013. Eligible patients were scheduled to undergo elective surgical interventions including joint (hip, knee arthroplasty), back (nucleotomy, spondylodesis), or urological surgery (cystectomy, prostatectomy, nephrectomy). Pain was assessed on an 11-point numerical rating scale (NRS) before, on postoperative day 2 and 6 months after surgery. Clinical information was collected with structured questionnaires and by telephone interview.ResultsSix hundred and forty-four patients gave informed consent, including 54.4 % men (mean age 62.2, SD 14.3). Higher preoperative pain scores were found in patients undergoing joint (mean 7.6; 95 % confidence interval [CI]: 7.2–8.0) and back surgery (mean 7.1, CI: 6.8–7.5) than in patients prior to urological surgery (mean 2.3; CI: 1.8–2.8). After 6 months, about 50 % of patients after joint or back surgery indicated pain levels ≥3/10, compared to 15.9 % of patients after urological surgery (p < .001). 35.3 % of the patients after joint surgery and 41.3 % after back surgery still use pain medication 6 months postoperatively, in contrast to 7.3 % of patients after urological surgery. 13.6 % of patients who underwent back surgery indicated the regular intake of opioids.ConclusionsOur results reveal that a significant percentage of patients undergoing procedures in joint or back surgery still need pain medication up to 6 months postoperatively due to ongoing pain symptoms. Improved monitoring of pain management is warranted, especially after discharge from hospital, to improve long-term results.Trial registrationClinicaltrials.gov (Identifier: NCT01488617); date of registration December 6th 2011.Electronic supplementary materialThe online version of this article (doi:10.1186/s12871-016-0261-7) contains supplementary material, which is available to authorized users.

IntroductionHip fracture surgery is associated with high in-hospital and 30-day mortality rates and serious adverse patient outcomes. Evidence from randomised controlled trials regarding effectiveness of spinal versus general anaesthesia on patient-centred outcomes after hip fracture surgery is sparse.Methods and analysisThe iHOPE study is a pragmatic national, multicentre, randomised controlled, open-label clinical trial with a two-arm parallel group design. In total, 1032 patients with hip fracture (>65 years) will be randomised in an intended 1:1 allocation ratio to receive spinal anaesthesia (n=516) or general anaesthesia (n=516). Outcome assessment will occur in a blinded manner after hospital discharge and inhospital. The primary endpoint will be assessed by telephone interview and comprises the time to the first occurring event of the binary composite outcome of all-cause mortality or new-onset serious cardiac and pulmonary complications within 30 postoperative days. In-hospital secondary endpoints, assessed via in-person interviews and medical record review, include mortality, perioperative adverse events, delirium, satisfaction, walking independently, length of hospital stay and discharge destination. Telephone interviews will be performed for long-term endpoints (all-cause mortality, independence in walking, chronic pain, ability to return home cognitive function and overall health and disability) at postoperative day 30±3, 180±45 and 365±60.Ethics and disseminationiHOPE has been approved by the leading Ethics Committee of the Medical Faculty of the RWTH Aachen University on 14 March 2018 (EK 022/18). Approval from all other involved local Ethical Committees was subsequently requested and obtained. Study started in April 2018 with a total recruitment period of 24 months. iHOPE will be disseminated via presentations at national and international scientific meetings or conferences and publication in peer-reviewed international scientific journals.Trial registration numberDRKS00013644; Pre-results

Opioid rotation can improve analgesia and patient satisfaction. The success of opioid rotation appears to depend on the magnitude of the initial dose, among other factors. Tables of equianalgesic doses should be considered no more than a rough guide for determining the dose of the new drug. Rotations to methadone should be carried out under clinical supervision in experienced hands.

The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions in ischemic endpoints, over the first 24 h, whereas there was a small excess of mortality. (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery [ATLANTIC, NCT01347580]).