Single-shot pectoral plane (PECs I and PECs II) blocks versus continuous local anaesthetic infusion analgesia or both after non-ambulatory breast-cancer surgery: a prospective, randomised, double-blind trial.

BACKGROUND: Pectoral plane blocks (PECs) are increasingly used in analgesia for patients undergoing breast surgery, and were recently found to be at least equivalent to single-shot paravertebral anaesthesia. However, there are no data comparing PECs with the popular practice of continuous local anaesthetic wound infusion (LA infusion) analgesia for breast surgery. Therefore, we compared the efficacy and safety of PECs blocks with LA infusion, or a combination of both in patients undergoing non-ambulatory breast-cancer surgery. METHODS: This single-centre, prospective, randomised, double-blind trial analysed 45 women to receive either PECs blocks [levobupivacaine 0.25%, 10 ml PECs I and levobupivacaine 0.25%, 20 ml PECs II (PECs group); LA infusion catheter (levobupivacaine 0.1% at 10 ml h-1 for 24 h (LA infusion group); or both (PECs and LA infusion)]. The primary outcome measure was area under the curve of the pain verbal rating score whilst moving vs time (AUC) over 24 h. Secondary outcomes included total opioid consumption at 24 h. RESULTS: AUC moving was mean (SD) 71 (34) mm h-1vs 58 (41) vs 23 (20) in PECs, LA infusion, and both, respectively; P=0.002. AUC at rest was also significantly lower in patients receiving both. The total 24 h opioid consumption [median (25-75%)] was 14 mg (9-26) vs 11 (8-24) vs 9 (5-11); P=0.4. No adverse events were observed. CONCLUSIONS: The combination of both pre-incisional PECs blocks and postoperative LA infusion provides better analgesia over 24 h than either technique alone after non-ambulatory breast-cancer surgery. CLINICAL TRIAL REGISTRATION: NCT 03024697.

Improving time to surgery for hip fracture patients. Impact of the introduction of an emergency theatre.

Hip fractures are a major cause of morbidity and mortality1. Surgery performed on the day of or after admission is associated with improved outcome2,3. An audit cycle was performed examining time to surgery for hip fracture patients. Our initial audit identified lack of theatre space as one factor delaying surgery. A dedicated daytime emergency theatre was subsequently opened and a re-audit was performed to assess its impact on time to surgery. Following the opening of the theatre, the proportion of patients with a delay to hip fracture surgery greater than 36 hours was reduced from 49% to 26% with lack of theatre space accounting for 23% (3 of 13) of delayed cases versus 28.6% (9 of 32) previously. 44% of hip fracture surgeries were performed in the emergency theatre during daytime hours, whilst in-hospital mortality rose from 4.6% to 6%. We conclude that access to an emergency theatre during daytime hours reduced inappropriate delays to hip fracture surgery.

Differential effects of serum from patients administered distinct anaesthetic techniques on apoptosis in breast cancer cells in vitro: a pilot study.

BACKGROUND: In vitro and retrospective clinical studies suggest an association between anaesthetic technique during primary breast cancer surgery and cancer outcome. Apoptosis is an important step in the mechanism of breast cancer metastasis, but whether it is influenced by anaesthetic technique is unknown. Using serum from breast cancer surgery patients randomized to receive distinct anaesthetic techniques, we investigated its effect on apoptosis in oestrogen receptor (ER)-negative breast cancer cells in vitro. METHODS: Women with biopsy-proven breast cancer were randomized to receive either propofol general anaesthesia with paravertebral analgesia (PPA) or standard sevoflurane general anaesthesia with opioid analgesia (SGA) in an ongoing, prospective clinical trial (NCT 00418457). Serum from a randomly selected subset of these patients (10 PPA and 10 SGA) who had donated 20 ml venous blood immediately before anaesthetic induction and at 1 h after operation was exposed to ER-negative MDA-MB-231 cells. Apoptosis was measured using ApoLive-Glo Multiplex Assay™. RESULTS: Exposure of MDA-MB-231 cells to postoperative serum of PPA patients resulted in higher luminescence ratio (apoptosis) than SGA patients, median (25-75%), 0.40 (0.35-0.43) compared with 0.22 (0.21-0.30), respectively (P=0.001). The luminescence ratio of postoperative serum from SGA was reduced compared with preoperative SGA 0.22 (0.21-0.30) compared with 0.3 (0.25-0.35) (P=0.045). CONCLUSIONS: Serum from patients given sevoflurane anaesthesia and opioids for primary breast cancer surgery reduces apoptosis in ER-negative breast cancer cells to a greater extent than serum from patients given propofol-paravertebral anaesthesia. Anaesthetic technique might affect the serum milieu in a manner that impacts cancer cell apoptosis, and thereby tumour metastasis.

Central auditory processing and social functioning following brain injury in children.

PRIMARY OBJECTIVE: To describe the percentage of children with central auditory processing disorders (CAPD) and examine the recovery patterns of social functional skills in children with and without CAPD admitted to inpatient rehabilitation following an acquired brain injury (ABI). RESEARCH DESIGN: Retrospective, descriptive. METHODS AND PROCEDURES: Repeated measures ANOVAs were used to examine overall differences in social functioning between groups, within groups and interaction effects for the Paediatric Evaluation of Disability Inventory (PEDI) Social Functional Skills and Caregiver Assistance scales for 31 children admitted to inpatient rehabilitation following ABI. MAIN OUTCOMES AND RESULTS: Significant overall effects were found in group differences and test occasions, but no significant interaction for either PEDI scale. Both groups showed significant intra-group changes between admission and discharge on both scales. CONCLUSIONS: Children with and without CAPD recovered social functional skills during inpatient rehabilitation. Children with CAPD were admitted and discharged with lower Social Function scores but demonstrated greater changes. The identification of CAPD during inpatient rehabilitation allows for appropriate discharge recommendations and realistic recovery expectations.

Further analysis of the role of spectrin repeat motifs in alpha-actinin dimer formation.

Protein constructs consisting of repeats 1-4, repeats 1-3 and repeats 2-4 of the rod domain of chicken alpha-actinin were expressed as fusion proteins in Escherichia coli. Based on the evidence of circular dichroism spectra and cooperative thermal unfolding profiles both truncated rod fragments were judged to have assumed the native structural fold. The thermal stabilities were in both cases significantly lower than that of the intact rod (repeats 1-4). Analyses by sedimentation equilibrium and velocity provided further evidence to show that fragment 1-4 is entirely dimeric in the concentration range of these experiments, resembling therefore the rod domain isolated by proteolytic digestion of native alpha-actinin. Fragment 2-4, and probably also 1-3, show concentration-dependent association, with dissociation constants, estimated by sedimentation equilibrium, in the 1-10 microM range. Thus, in confirmation of earlier work, all four repeats are required to generate a maximally stable anti-parallel dimer (Kd approximately 10 pM), suggesting the presence of binding sites in all of them to allow for aligned pairing.

Physical properties of dystrophin rod domain.

We have prepared two fragments of the human dystrophin rod domain, each containing eight spectrin-like repeating units, by expression in Escherichia coli. The first corresponds to the central portion of the rod, the other to three repeats from the N-terminal end, fused to five repeats from the C-terminal end. The latter makes up the entire mutant rod, found in a patient with mild (Becker-type) muscular dystrophy. Both fragments were found to possess an ordered, stable structure, and had the form of short rod-like particles in the electron microscope. Molecular weight determinations by sedimentation equilibrium revealed that both polypeptides were monomeric in solution, suggesting that the dystrophin rod domain is incapable of forming an antiparallel homodimer. This supports the inference from sequence analyses [Winder et al., 1995: FEBS Lett. 369:27-33, 1996: Biochem. Soc. Trans. 24:2805] that the dystrophin rod domain lacks the arrangement of sites required for lateral self-association, and that dystrophin, unlike the other known proteins of the spectrin superfamily, may thus exist as a monomer.

Association of structural repeats in the alpha-actinin rod domain. Alignment of inter-subunit interactions.

Fragments of the rod domain of chicken alpha-actinin, which comprises four spectrin-like repeat sequences, have been prepared by expression in Escherichia coli. Electron microscopy reveals that all products containing three or four complete repeats are rod-like. Self-association of fragments was detected by chemical cross-linking and analytical equilibrium sedimentation. The intact rod domain forms a stable dimmer, which does not dissociate measurably in the accessible concentration range. Elimination of either terminal repeat (repeat 1 or repeat 4) greatly diminishes the extent of dimerisation. The fragment comprising repeats 1-3 dimerises appreciably, with an association constant estimated from the sedimentation equilibrium distribution of approximately 5 x 10(5) M-1. The fragment made up of repeats 2-4 dimerises to a small extent, but also forms aggregates at high concentrations. The results are most easily reconciled with an aligned structure for the rod domain in solution, in which repeat 1 associates with repeat 4 of the partnering chain, and repeat 2 with repeat 3, rather than with a staggered structure, in which one of the terminal repeats does not participate in dimerisation. Possible explanations for the apparent difference observed between the alpha-actinin rod structure in solution and in two-dimensional crystalline arrays are examined.