A HER2 selective theranostic agent for surgical resection guidance and photodynamic therapy.

In many cancers early intervention involves surgical resection of small localised tumour masses. Inadequate resection leads to recurrence whereas overzealous treatment can lead to organ damage. This work describes production of a HER2 targeting antibody Fab fragment dual conjugated to achieve both real time near-infrared fluorescent imaging and photodynamic therapy. The use of fluorescence emission from a NIR-dye could be used to guide resection of tumour bulk, for example during endoscopic diagnosis for oesophago-gastric adenocarcinoma, this would then be followed by activation of the photodynamic therapeutic agent to destroy untreated localised areas of cancer infiltration and tumour infiltrated lymph nodes. This theranostic agent was prepared from the Fab fragment of trastuzumab initially by functional disulfide re-bridging and site-specific click reaction of a NIR-dye. This was followed by further reaction with a novel pre-activated form of the photosensitiser chlorin e6 with the exposed fragments' lysine residues. Specific binding of the theranostic agent was observed in vitro with a HER2 positive cell line and cellular near-infrared fluorescence was observed with flow cytometry. Specific photo-activity of the conjugates when exposed to laser light was observed with HER2 positive but not HER2 negative cell lines in vitro, this selectivity was not seen with the unconjugated drug. This theranostic agent demonstrates that two different photo-active functions can be coupled to the same antibody fragment with little interference to their independent activities.

Randomized clinical trial of the impact of surgical ward-care checklists on postoperative care in a simulated environment.

BACKGROUND: Complications are a common and accepted risk of surgery. Failure to optimize the management of patients who suffer postoperative morbidity may result in poorer surgical outcomes. This study aimed to evaluate a checklist-based tool to improve and standardize care of postoperative complications. METHODS: Surgical trainees conducted baseline ward rounds of three patients with common postoperative complications in a high-fidelity simulated ward environment. Subjects were randomized to intervention or control groups, and final ward rounds were conducted with or without the aid of checklists for management of postoperative complications. Adherence to critical care processes was assessed, in addition to technical (Surgical Ward-care Assessment Tool, SWAT) and non-technical (Ward NOn-TECHnical Skills (W-NOTECHS) scale) performance. Subjects completed a feedback questionnaire regarding their perception of the checklists. RESULTS: Twenty trainees completed 120 patient assessments. All intervention group subjects opted to use the checklists, resulting in significantly fewer critical errors compared with controls (median (i.q.r.) 0 (0-0) versus 60 (40-73) per cent; P < 0·001). The intervention group demonstrated improved patient management (SWAT-M) (P < 0·001) and non-technical skills (P = 0·043) between baseline and final ward rounds, whereas controls did not (P = 0·571 and P = 0·809 respectively). A small learning effect was seen with improvement in patient assessment (SWAT-A) in both groups (P < 0·001). Intervention group subjects found checklists easy and effective to use, and would want them used for their own care if they were to experience postoperative complications. CONCLUSION: Checklist use resulted in significantly improved standardization, evidence-based management of postoperative complications, and quality of ward rounds. Simulation-based piloting aided appropriate use of checklists and staff engagement. Checklists represent a low-cost intervention to reduce rates of failure to rescue and to improve patient care.

Meta-analysis of the effect of postoperative in-hospital morbidity on long-term patient survival.

BACKGROUND: Major surgery is associated with high rates of postoperative complications, many of which are deemed preventable. It has been suggested that these complications not only present a risk to patients in the short term, but may also reduce long-term survival. The aim of this review was to examine the effects of postoperative complications on long-term survival. METHODS: MEDLINE, Web of Science and reference lists of relevant articles were searched up to July 2013. Studies assessing only procedure-specific, or technical failure-related, complications were excluded, as were studies of poor methodological quality. Meta-analysis was performed using a random-effects model. Risk of bias was assessed using funnel plots. RESULTS: Eighteen eligible studies were included, comprising results for 134 785 patients with an overall complication rate of 22·6 (range 10·6-69) per cent. The studies included operations for both benign and malignant disease. Median follow-up was 43 (range 28-96) months. Meta-analysis demonstrated reduced overall survival after any postoperative complication for ten studies with eligible data (20 755 patients), with a hazard ratio (HR) of 1·28 (95 per cent confidence interval 1·21 to 1·34). Similar results were found for overall survival following infectious complications: HR 1·92 (1·50 to 2·35). In analyses of disease-free survival the HR was 1·26 (1·10 to 1·42) for all postoperative complications and 1·55 (1·12 to 1·99) for infectious complications. Inclusion of poor-quality studies in a sensitivity analysis had no effect on the results. CONCLUSION: Postoperative complications have a negative effect on long-term survival. This relationship appears to be stronger for infectious complications.

Prenatal diagnosis of idiopathic infantile arterial calcification with hydrops fetalis.

Idiopathic infantile arterial calcification (IIAC) is a rare and nearly always fatal disorder. To date, prenatal diagnosis has been reported in fewer than 10 cases. We describe a series of three cases in which the diagnosis of IIAC was made at 23, 25 and 29 weeks' gestation. All three cases presented with a normal anatomy scan at 20 weeks' gestation with an echogenic intracardiac focus. Follow-up scans showed generalized hyperechogenicity and calcification of the walls of the large arteries, particularly the aorta and the iliac arteries. All cases developed hydrops fetalis with cardiomegaly and polyhydramnios later in gestation, resulting in intrauterine fetal death in two cases and neonatal death immediately following delivery in the third. This is the largest case series and the earliest gestational age of prenatal diagnosis of IIAC reported to date. When surveying for the disease, serial scans are important, perhaps from 20 weeks' gestation, with close examination of the iliac and aortic arteries. Detection of echogenic intracardiac focus could be an early marker in patients with a family history of the disease.