Cancellation of elective surgical procedures in the university teaching hospital center Yalgado Ouedraogo in Burkina Faso: incidence, reasons and proposals for improvement

Background: Cancellation of scheduled surgery leads to operating theatre under-occupancy and is recognised as a major cause of emotional trauma to patients and their families. This study aimed to assess the incidence of elective surgery cancellation in order to make proposals for healthcare improvement.Methods: A prospective study was undertaken on cancellation of scheduled surgery in the general surgery service. Cancellation is considered to have occurred when planned surgery did not take place on the day it was scheduled and recognised as ‘final’ when it was no longer considered at a later date. Cancellations were classed as ‘avoidable’ or ‘unavoidable’.Results: A total of 103 surgeries were scheduled for patients with an average age of 41.1 years. Abdominal surgery (36.9%) dominated and 63.1% (n = 65) of the operations were scheduled. Some 36.9% (n = 38) of interventions were delayed, of which 9.7% (n = 10) were definitively cancelled and 27.2% (n = 28) were carried forward. Half of the cancellations (47.4%) were related to equipment and 31.6% related to patient factors. Hospital-related cancellation accounted for 63.9%. Cancellation was avoidable in 68.5% of cases. A financial cause was relevant for 16.6% (n = 6) and 2.6% of cancellations were due to a ‘long preceding intervention’.Conclusion: The impact of cancellation is high and better organisation and communication between relevant role players within the operating theatre should reduce unnecessary cancellation.Keywords: cancellation, elective surgery, operating theatr

Metastasis of hormone-independent breast cancer to lung and bone is decreased by α-difluoromethylornithine treatment

INTRODUCTION: Polyamines affect proliferation, differentiation, migration and apoptosis of cells, indicating their potential as a target for cancer chemotherapy. Ornithine decarboxylase converts ornithine to putrescine and is the rate-limiting step in polyamine synthesis. α-Difluoromethylornithine (DFMO) irreversibly inhibits ornithine decarboxylase and MDA-MB-435 human breast cancer metastasis to the lung without blocking orthotopic tumor growth. This study tested the effects of DFMO on orthotopic tumor growth and lung colonization of another breast cancer cell line (MDA-MB-231) and the effects on bone metastasis of MDA-MB-435 cells. METHODS: MDA-MB-231 cells were injected into the mammary fat pad of athymic mice. DFMO treatment (2% per orally) began at the day of tumor cell injection or 21 days post injection. Tumor growth was measured weekly. MDA-MB-231 cells were injected into the tail vein of athymic mice. DFMO treatment began 7 days prior to injection, or 7 or 14 days post injection. The number and incidence of lung metastases were determined. Green fluorescent protein-tagged MDA-MB-435 cells were injected into the left cardiac ventricle in order to assess the incidence and extent of metastasis to the femur. DFMO treatment began 7 days prior to injection. RESULTS: DFMO treatment delayed MDA-MB-231 orthotopic tumor growth to a greater extent than growth of MDA-MB-435 tumors. The most substantial effect on lung colonization by MDA-MB-231 cells occurred when DFMO treatment began 7 days before intravenous injection of tumor cells (incidence decreased 28% and number of metastases per lung decreased 35–40%). When DFMO treatment began 7 days post injection, the incidence and number of metastases decreased less than 10%. Surprisingly, treatment initiated 14 days after tumor cell inoculation resulted in a nearly 50% reduction in the number of lung metastases without diminishing the incidence. After intracardiac injection, DFMO treatment decreased the incidence of bone metastases (55% vs 87%) and the area occupied by the tumor (1.66 mm(2 )vs 4.51 mm(2), P < 0.05). CONCLUSION: Taken together, these data demonstrate that DFMO exerts an anti-metastatic effect in more than one hormone-independent breast cancer, for which no standard form of biologically-based treatment exists. Importantly, the data show that DFMO is effective against metastasis to multiple sites and that treatment is generally more effective when administered early

In Silico and In Vitro Investigations of the Mutability of Disease-Causing Missense Mutation Sites in Spermine Synthase

Spermine synthase (SMS) is a key enzyme controlling the concentration of spermidine and spermine in the cell. The importance of SMS is manifested by the fact that single missense mutations were found to cause Snyder-Robinson Syndrome (SRS). At the same time, currently there are no non-synonymous single nucleoside polymorphisms, nsSNPs (harmless mutations), found in SMS, which may imply that the SMS does not tolerate amino acid substitutions, i.e. is not mutable.To investigate the mutability of the SMS, we carried out in silico analysis and in vitro experiments of the effects of amino acid substitutions at the missense mutation sites (G56, V132 and I150) that have been shown to cause SRS. Our investigation showed that the mutation sites have different degree of mutability depending on their structural micro-environment and involvement in the function and structural integrity of the SMS. It was found that the I150 site does not tolerate any mutation, while V132, despite its key position at the interface of SMS dimer, is quite mutable. The G56 site is in the middle of the spectra, but still quite sensitive to charge residue replacement.The performed analysis showed that mutability depends on the detail of the structural and functional factors and cannot be predicted based on conservation of wild type properties alone. Also, harmless nsSNPs can be expected to occur even at sites at which missense mutations were found to cause diseases

Fast Homozygosity Mapping and Identification of a Zebrafish ENU-Induced Mutation by Whole-Genome Sequencing

Forward genetics using zebrafish is a powerful tool for studying vertebrate development through large-scale mutagenesis. Nonetheless, the identification of the molecular lesion is still laborious and involves time-consuming genetic mapping. Here, we show that high-throughput sequencing of the whole zebrafish genome can directly locate the interval carrying the causative mutation and at the same time pinpoint the molecular lesion. The feasibility of this approach was validated by sequencing the m1045 mutant line that displays a severe hypoplasia of the exocrine pancreas. We generated 13 Gb of sequence, equivalent to an eightfold genomic coverage, from a pool of 50 mutant embryos obtained from a map-cross between the AB mutant carrier and the WIK polymorphic strain. The chromosomal region carrying the causal mutation was localized based on its unique property to display high levels of homozygosity among sequence reads as it derives exclusively from the initial AB mutated allele. We developed an algorithm identifying such a region by calculating a homozygosity score along all chromosomes. This highlighted an 8-Mb window on chromosome 5 with a score close to 1 in the m1045 mutants. The sequence analysis of all genes within this interval revealed a nonsense mutation in the snapc4 gene. Knockdown experiments confirmed the assertion that snapc4 is the gene whose mutation leads to exocrine pancreas hypoplasia. In conclusion, this study constitutes a proof-of-concept that whole-genome sequencing is a fast and effective alternative to the classical positional cloning strategies in zebrafish

Dre-miR-2188 Targets Nrp2a and Mediates Proper Intersegmental Vessel Development in Zebrafish Embryos

BACKGROUND: MicroRNAs (miRNAs) are a class of small RNAs that are implicated in the control of eukaryotic gene expression by binding to the 3'UTR of target mRNAs. Several algorithms have been developed for miRNA target prediction however, experimental validation is still essential for the correct identification of miRNA targets. We have recently predicted that Neuropilin2a (Nrp2a), a vascular endothelial growth factor receptor which is essential for normal developmental angiogenesis in zebrafish, is a dre-miR-2188 target. METHODOLOGY: Here we show that dre-miR-2188 targets the 3'-untranslated region (3'UTR) of Nrp2a mRNA and is implicated in proper intersegmental vessel development in vivo. Over expression of miR-2188 in zebrafish embryos down regulates Nrp2a expression and results in intersegmental vessel disruption, while its silencing increases Nrp2a expression and intersegmental vessel sprouting. An in vivo GFP sensor assay based on a fusion between the GFP coding region and the Nrp2a 3'UTR confirms that miR-2188 binds to the 3'UTR of Nrp2a and inhibits protein translation. CONCLUSIONS: We demonstrate that miR-2188 targets Nrp2a and affects intersegmental vessel development in zebrafish embryos

Correlating Global Gene Regulation to Angiogenesis in the Developing Chick Extra-Embryonic Vascular System

International audienceBACKGROUND: Formation of blood vessels requires the concerted regulation of an unknown number of genes in a spatial-, time- and dosage-dependent manner. Determining genes, which drive vascular maturation is crucial for the identification of new therapeutic targets against pathological angiogenesis. METHOLOGY/PRINCIPAL FINDINGS: We accessed global gene regulation throughout maturation of the chick chorio-allantoic membrane (CAM), a highly vascularized tissue, using pan genomic microarrays. Seven percent of analyzed genes showed a significant change in expression (>2-fold, FDR<5%) with a peak occurring from E7 to E10, when key morphogenetic and angiogenic genes such as BMP4, SMO, HOXA3, EPAS1 and FGFR2 were upregulated, reflecting the state of an activated endothelium. At later stages, a general decrease in gene expression occurs, including genes encoding mitotic factors or angiogenic mediators such as CYR61, EPAS1, MDK and MYC. We identified putative human orthologs for 77% of significantly regulated genes and determined endothelial cell enrichment for 20% of the orthologs in silico. Vascular expression of several genes including ENC1, FSTL1, JAM2, LDB2, LIMS1, PARVB, PDE3A, PRCP, PTRF and ST6GAL1 was demonstrated by in situ hybridization. Up to 9% of the CAM genes were also overexpressed in human organs with related functions, such as placenta and lung or the thyroid. 21-66% of CAM genes enriched in endothelial cells were deregulated in several human cancer types (P<.0001). Interfering with PARVB (encoding parvin, beta) function profoundly changed human endothelial cell shape, motility and tubulogenesis, suggesting an important role of this gene in the angiogenic process. CONCLUSIONS/SIGNIFICANCE: Our study underlines the complexity of gene regulation in a highly vascularized organ during development. We identified a restricted number of novel genes enriched in the endothelium of different species and tissues, which may play crucial roles in normal and pathological angiogenesis

Polyamines and cancer: old molecules, new understanding

The amino-acid-derived polyamines have long been associated with cell growth and cancer, and specific oncogenes and tumour-suppressor genes regulate polyamine metabolism. Inhibition of polyamine synthesis has proven to be generally ineffective as an anticancer strategy in clinical trials, but it is a potent cancer chemoprevention strategy in preclinical studies. Clinical trials, with well-defined goals, are now underway to evaluate the chemopreventive efficacy of inhibitors of polyamine synthesis in a range of tissues

A comparison of the training value of two types of anesthesia simulators: Computer screen-based and mannequin-based simulators

In this study, we compared two different training simulators (the computer screen-based simulator versus the full-scale simulator) with respect to training effectiveness in anesthesia residents. Participants were evaluated in the management of a simulated preprogrammed scenario of anaphylactic shock using two variables: treatment score and diagnosis time. Our results showed that simulators can contribute significantly to the improvement of performance but that learning in treating simulated crisis situations such as anaphylactic shock did not significantly vary between full-scale and computer screen-based simulators. Consequently, the initial decision on whether to use a full-scale or computer screen-based training simulator should be made on the basis of cost and learning objectives rather than on the basis of technical or fidelity criteria. Our results support the contention that screen-based simulators are good devices to acquire technical skills of crisis management. Mannequin-based simulators would probably provide better training for behavioral aspects of crisis management, such as communication, leadership, and interpersonal conflicts, but this was not tested in the current study. IMPLICATIONS: We compared two different training simulators (computer screen-based versus full-scale) for training anesthesia residents to better document the effectiveness of such devices as training tools. This is an important issue, given the extensive use and the high cost of mannequin-based simulators in anesthesiology

Postoperative use of nasal intermittent positive pressure in a patient with spinal muscular atrophy type II.

We report the successful use of nasal intermittent positive pressure ventilation (NIPPV) in the perioperative period of a 51 yr-old woman with a type II spinal muscular atrophy (SMA II). The patient was treated chronically with nocturnal NIPPV at home and scheduled for endoscopic retrograde cholangiopancreatography (ERCP) under general anesthesia. Some criteria of difficult intubation were present (forced mouth opening of 1.5 cm, short neck and thyromental distance of 5 cm). Nasal endotracheal fiberoptic intubation during spontaneous breathing under sedation with propofol was performed. The ERCP procedure was conducted without complications. At the end of the procedure, IPPV was maintained until recovery of respiratory function. After extubation, NIPPV was continued in the recovery room. The patient was discharged from the post-anesthesia care unit 4 hours after the procedure. Management of patients with SMA remains a challenge and clinicians must be aware that the use of NIPPV may be a useful and life-saving tool in the perioperative period for these patients

Mivacurium chloride for short laparoscopic procedures.

We have studied the effects of mivacurium after induction of anesthesia with fentanyl-propofol in healthy adult women. Anesthesia was maintained with nitrous oxide in oxygen and continuous infusion of propofol (6-10 mg/kg/hr.). A myorelaxograph (Datex NMT 100) measuring the responses of the adductor pollicis to Train of Four (TOF) stimulations of the ulnar nerve was installed after induction. Three bolus dosages of mivacurium were administered just after induction: 0.15 mg/kg (group A), 0.17 mg/kg (group B) and 0.19 mg/kg (group C). Intubation was attempted at 75% TI-suppression. The conditions of intubation were good to excellent in the three groups except for one patient in group A (0.15 mg/kg). Successful intubation was performed faster in group C(p = 0.017). The curarization time was significantly longer in group C(0.19 mg/kg) vs the other groups (p = 0.002). As soon as the first signs of recovery (TI increment) appeared, a continuous infusion of mivacurium (10 micrograms/kg/min) was started to maintain a complete neuromuscular block. After stopping the continuous infusion, there were no differences in spontaneous recovery between groups A and B but patients from group C showed a lenghtening of the recovery time. There is no effect of the different bolus dosages on vital signs. We conclude that a bolus dosage of 0.19 mg/kg after induction of anesthesia with fentanyl-propofol offers the best choice when a rapid sequence of induction is required. Mivacurium could be an interesting muscle relaxant in one-day surgery even if a risk of prolonged curarization exists due to its degradation by plasma cholinesterases