Dealing with complications in interventional radiology.

It is widely accepted that most misadventures, which lead to harm have not occurred because of a single individual but rather due to a failure of process that results in healthcare workers making mistakes. This failure of process and the pervasiveness of adverse events is just as prevalent in Interventional Radiology (IR) as it is in other specialities. The true prevalence and prevailing aetiology of complications in IR are not exactly known as there is a paucity of investigative literature into this area; especially when compared with other more established disciplines such as Surgery. Some IR procedures have a higher risk profile than others. However, published data suggests that many adverse events in IR are preventable (55-84%) and frequently involve a device related complication such as improper usage or malfunction. This article aims to discuss factors that contribute to complications in IR along with tools and strategies for dealing with them to achieve optimal patient outcomes.

Impact of site of occlusion in proximal splenic artery embolisation for blunt splenic trauma.

BACKGROUND: Proximal splenic artery embolisation (PSAE) can be performed in stable patients with Association for the Surgery of Trauma (AAST) grade III-V splenic injury. PSAE reduces splenic perfusion but maintains viability of the spleen and pancreas via the collateral circulation. The hypothesized ideal location is between the dorsal pancreatic artery (DPA) and great pancreatic artery (GPA). This study compares the outcomes resulting from PSAE embolisation in different locations along the splenic artery. MATERIALS AND METHODS: Retrospective review was performed of PSAE for blunt splenic trauma (2015-2020). Embolisation locations were divided into: Type I, proximal to DPA; Type II, DPA-GPA; Type III, distal to GPA. Fifty-eight patients underwent 59 PSAE: Type I (7); Type II (27); Type III (25). Data was collected on technical and clinical success, post-embolisation pancreatitis and splenic perfusion. Statistical significance was assessed using a chi-squared test. RESULTS: Technical success was achieved in 100% of cases. Clinical success was 100% for Type I/II embolisation and 88% for Type III: one patient underwent reintervention and two had splenectomies for ongoing instability. Clinical success was significantly higher in Type II embolisation compared to Type III (p = 0.02). No episodes of pancreatitis occurred post-embolisation. Where post-procedural imaging was obtained, splenic perfusion remained 100% in Type I and II embolisation and 94% in Type III. Splenic perfusion was significantly higher in the theorized ideal Type II group compared to Type I and III combined (p = 0.01). CONCLUSION: The results support the proposed optimal embolisation location as being between the DPA and GPA.

Association between non-vascularised bone graft failure and compartment of the defect in mandibular reconstruction: a systematic review and meta-analysis.

Controversy exists regarding the influence of the graft placement site in the mandible on the success of non-vascularised bone grafts. In this study, we examine the association between the compartment of the mandibular defect and the bone graft failure rate. A systematic literature review and meta-analysis was performed using MEDLINE, Embase, and Cochrane databases. Failure rates according to the compartment of mandibular defect were extracted and analysed by meta-analysis. The Newcastle-Ottawa Scale was used to assess the quality of the studies, and publication bias was evaluated using funnel plots. The search strategy identified 27 publications. After screening, five were selected for review. Based on the result of comparison among these five, we found no significant statistical association between the bone graft failure rate and compartment of mandibular defect, although further investigation of prospective randomised cohort studies is required.

Risk factors for the delayed diagnosis of extrapulmonary TB.

BACKGROUND: Extrapulmonary TB (EPTB) is more difficult to diagnose than pulmonary TB. The delayed management of EPTB can lead to complications and increase the socio-economic burden.METHODS: Patients newly diagnosed with EPTB were retrospectively enrolled from 11 general hospitals in South Korea from January 2017 to December 2018. The basic characteristics of patients were described. Univariable and multivariable analyses were performed between early and delayed diagnosis groups to identify risk factors for delayed diagnosis and treatment in EPTB.RESULTS: In total, 594 patients were enrolled. Lymph node TB (28.3%) was the predominant form, followed by abdominal (18.4%) and disseminated TB (14.5%). Concurrent lung involvement was 17.8%. The positivity of diagnostic tests showed no significant difference between the two groups. Acute clinical manifestations in disseminated, pericardial and meningeal TB, and immunosuppression were associated with early diagnosis. Delayed diagnosis was associated with outpatient clinic visits, delayed sample acquisition and diagnostic departments other than infection or pulmonology.CONCLUSION: The delay in diagnosis and treatment of EPTB was not related to differences in microbiological characteristics of Mycobacterium tuberculosis itself; rather, it was due to the indolent clinical manifestations that cause referral to non-TB-specialised departments in the outpatient clinic and delay the suspicion of TB and diagnostic testing.

Enhanced antimicrobial stewardship based on rapid phenotypic antimicrobial susceptibility testing for bacteraemia in patients with haematological malignancies: a randomized controlled trial.

OBJECTIVES: Recently, rapid phenotypic antimicrobial susceptibility testing (AST) based on microscopic imaging analysis has been developed. The aim of this study was to determine whether implementation of antimicrobial stewardship programmes (ASP) based on rapid phenotypic AST can increase the proportion of patients with haematological malignancies who receive optimal targeted antibiotics during early periods of bacteraemia. METHODS: This randomized controlled trial enrolled patients with haematological malignancies and at least one positive blood culture. Patients were randomly assigned 1:1 to conventional (n = 60) or rapid phenotypic (n = 56) AST. The primary outcome was the proportion of patients receiving optimal targeted antibiotics 72 hr after blood collection for culture. RESULTS: The percentage receiving optimal targeted antibiotics at 72 hr was significantly higher in the rapid phenotypic AST group (45/56, 80.4%) than in conventional AST group (34/60, 56.7%) (relative risk (RR) 1.42, 95% confidence interval (CI) 1.09-1.83). The percentage receiving unnecessary broad-spectrum antibiotics at 72 hr was significantly lower (7/26, 12.5% vs 18/60, 30.0%; RR 0.42, 95% CI 0.19-0.92) and the mean time to optimal targeted antibiotic treatment was significantly shorter (38.1, standard deviation (SD) 38.2 vs 72.8, SD 93.0 hr; p < 0.001) in the rapid phenotypic AST group. The mean time from blood collection to the AST result was significantly shorter in the rapid phenotypic AST group (48.3, SD 17.6 vs 83.1, SD 22.2 hr). DISCUSSION: ASP based on rapid phenotypic AST can rapidly optimize antibiotic treatment for bacteraemia in patients with haematological malignancy. Rapid phenotypic AST can improve antimicrobial stewardship in immunocompromised patients.

Transcatheter embolisation of type 1 endoleaks after endovascular aortic aneurysm repair with Onyx: when no other treatment option is feasible.

Type 1 endoleaks following endovascular aortic aneurysm repair are associated with poor outcomes and re-intervention is recommended as soon as possible after diagnosis. When standard endovascular or surgical treatment options are unsuitable due to severe co-morbidity or adverse anatomic factors, patients can be treated by transcatheter embolisation of the endoleak itself. We describe six such patients with proximal and distal type 1 endoleaks, who have been successfully treated by transcatheter embolisation with Onyx. The embolisation technique, advantages of using this relatively novel liquid embolic agent and potential pitfalls are discussed.

Technique and outcomes of isolated limb infusion for locally advanced malignant melanoma--a radiological perspective.

AIM: Isolated limb infusion (ILI) is a novel, minimally invasive technique for delivering high-dose regional chemotherapy in patients with recurrent and in-transit melanoma. The aim of this study was to review our single-centre experience in treating eleven patients. We emphasize the role of radiologists in setting up this service, including pre-treatment workup and placement of vascular catheters. MATERIALS AND METHODS: A retrospective analysis of 11 patients who underwent 12 procedures between 2005 and 2009 was performed. Pre-procedural staging computed tomography (CT), CT angiography, and duplex studies were performed. All patients received a cytotoxic combination of melphalan and actinomycin-D via radiologically placed arterial and venous catheters in the affected limb under mild hyperthermic conditions. The outcome measures include response rates, limb toxicity, complications, and survival. RESULTS: All patients were female with a mean age of 72 years. Three patients had American Joint Committee on Cancer (AJCC) stage IIIB melanoma, seven had stage IIIC melanoma, and one had a stage IIIB Merkel cell tumour. Complete response was seen in five patients (46%), partial response in four (36%), and progressive disease in two (18%). One patient developed grade 4 toxicity requiring a fasciotomy and another experienced systemic toxicity. CONCLUSION: These outcomes are comparable to previous studies and shows that ILI is effective in locoregional control of unresectable melanoma. It is a relatively safe procedure but not without risk. Our experience shows the importance of radiological input to ensure safe and effective delivery of services.

Developments in subintimal angioplasty in the infrainguinal segment.

Since it was first described in 1990, subintimal angioplasty (SIA) has become an established percutaneous procedure for the treatment of symptomatic lower limb arterial occlusions. The concept of this technique is to create a dissection in the subintimal plane in order to cross an occluded intraluminal segment, then to re-enter the true lumen of the patent distal artery. Balloon dilatation of this subintimal channel results in a new extraluminal lumen that is free of atheromatous plaque. It is a safe and effective procedure with advantages over intraluminal angioplasty and open surgery, thereby increasing the scope of endovascular therapy to include complex infrapopliteal occlusions and high-risk patients with limb-threatening ischaemia who are unsuitable for surgical revascularization. It has good primary success rates, long-term outcomes and does not compromise future surgical revascularization, resulting in a paradigm shift in the management of lower limb ischemia with many centres adopting SIA as first-line therapy. This article aims to review the indications of SIA, variations and developments in the technique, outcomes and factors affecting patency, and complications associated with the procedure.

Cardiac Characteristics of Transgenic Mice Overexpressing Refsum Disease Gene-Associated Protein within the Heart.

Arrhythmia is a common cardiac symptom of Refsum disease. Recently, we identified a novel neuron-specific PAHX-associated protein (PAHX-AP1), which binds to the Refsum disease gene (PAHX). In this report, we developed heart-targeted transgenic (TG) mice under the control of alpha-myosin heavy chain promoter to determine whether cardiac overexpression of PAHX-AP1 provokes cardiac involvement symptoms. Northern and in situ hybridization analyses revealed PAHX-AP1 transcript was overexpressed in TG atrium, especially in the sinoatrial node. TG mice showed tachycardia, and tachyarrhythmia was observed in 20% of TG mice. Isolated TG atria showed higher frequency beating and were more sensitive to aconitine-induced tachyarrhythmia than the wild-type, and 40% of the TG atria showed irregular beating. Action potential duration in TG atrial fiber was shortened much more than the wild-type. Systemic administration of arrhythmogenic agents induced arrhythmia in TG mice, while no arrhythmia with the same dose in nonTG mice. Our results indicate that the chronic atrial tachycardia by overexpressed neuron-specific PAHX-AP1 transgene in atrium may be responsible for the increased susceptibility to arrhythmia.

Current multimodality management of infectious intracranial aneurysms.

OBJECTIVE: To implement an algorithm for and assess multimodality (medical, endovascular, and microsurgical) treatment of patients with infectious intracranial aneurysms. METHODS: Twenty patients with 27 infectious aneurysms were treated during a 10-year period. Bacterial endocarditis was the most common cause (65%). Most aneurysms presented with rupture (75%), and the middle cerebral artery was the most common location (70%). RESULTS: Five patients were treated endovascularly, with direct coiling for three patients and parent artery occlusion for two patients. Ten patients (15 aneurysms) were treated surgically, with 6 aneurysms being trapped/resected, 2 trapped/bypassed, 4 clipped, and 3 wrapped. Five patients were treated medically. Treatment-associated neurological morbidity was observed for two patients (10%), and two patients died (10%). Good outcomes were observed for 16 patients (80%). CONCLUSION: Factors that guide management decisions for these patients include aneurysm rupture, hematomas with increased intracranial pressure, and the eloquence of brain tissue supplied by the parent artery. Patients with unruptured infectious aneurysms are initially treated medically, with antibiotics and serial angiography. Patients with ruptured aneurysms that are not associated with hematomas and that do not involve eloquent vascular territory are treated endovascularly. Patients with ruptured aneurysms are treated surgically when there is a hematoma or the risk of ischemic complications in eloquent territory. Therefore, endovascular therapy is the first option for patients in stable condition with ruptured aneurysms; surgical therapy is the first option for patients in unstable condition with ruptured aneurysms and the second option for patients in stable condition who experience failure of endovascular therapy. Medically treated patients with enlarging or dynamic unruptured aneurysms also require direct surgical or endovascular intervention. Favorable patient outcomes can be achieved with this multimodality management.

Structure and expression of the Arabidopsis thaliana homeobox gene Athb-12.

We have isolated the Arabidopsis thaliana homeobox gene Athb-12, determined its structure and activation domain, demonstrated that its promoter is inducible in response to abscisic acid (ABA) treatment, and characterized the cellular distribution of its transcripts. The single intron of the gene interrupted the leucine-zipper domain region. The 5' regulatory region of Athb-12 can drive beta-glucuronidase (GUS) expression in tobacco transgenic plants. Athb-12 gene expression was further examined using in situ hybridization to determine the cellular distribution of Athb-12 transcripts during ABA induction. A complex pattern of Athb-12 expression was observed, often associated with regions of developing vascular tissues. Analysis of chimeras constructed from Athb-12 and the DNA-binding domain of the Saccharomyces cerevisiae transcription factor GAL4 revealed that the activation domain of Athb-12 lies in the C-terminal region (amino acids 180 to 235). Taken together, our data suggest that Athb-12 is a transcriptional activator important in regulating certain developmental processes as well as in the plant's response to water stress involving ABA-mediated gene expression.

The Bradyrhizobium japonicum hsfA gene exhibits a unique developmental expression pattern in cowpea nodules.

The Bradyrhizobium japonicum host-specific fixation gene hsfA was identified as essential for nitrogen fixation on cowpea, but not required for nitrogen fixation on soybean or siratro. The DNA sequence of the hsfA promoter contains a consensus RpoN, -24/-12 binding site, suggesting the involvement of a regulatory protein that binds to an upstream activating sequence (UAS). To further explore the regulation of this interesting gene, serial deletions of the hsfA promoter were made and fused with the beta-glucuronidase (GUS) gene. The HsfA3 deletion, containing 60 bp 5' of the -24/-12 sequence, showed a similar level of GUS expression to that shown by the longest fusion construct (HsfA1), containing 464 bp of upstream sequence. In contrast, the HsfA4-GUS fusion, containing only 20 bp 5' of the -24/-12 region, showed no GUS activity, delimiting the location of a putative UAS to a 40-bp region. During nodule development, GUS expression first appeared in nodules 12 days postinoculation (dpi) and reached a maximum level of expression in approximately 17-day-old nodules. By 28 dpi, HsfA-GUS expression had returned to a low, basal level. These data were consistent with the detection of hsfA mRNA by in situ hybridization in 17-day-old nodules, but not in 28-day-old nodules. In contrast to the stage-specific expression in cowpea, HsfA-GUS expression increased with nodule development in HsfA3-inoculated soybean. These data indicate that HsfA expression is regulated in cowpea in a unique developmental manner and that the DNA regulatory regions that control this expression are confined to a short, promoter-proximal region.

Insulin stimulates production of nitric oxide via ERK in osteoblast cells.

We explored to determine if iNOS could be induced by insulin in osteoblast-like UMR-106 cells. Insulin (100 nM) stimulated nitric oxide production by twofold and significantly increased iNOS mRNA and protein levels. Insulin also increased collagen synthesis, but had little effect on alkaline phosphatase activity. In contrast, IGF-1 had little effect on NO production below 10 nM and it stimulated NO production by only 57% at 100 nM. IGF-1 had little effect on collagen levels, whereas it inhibited alkaline phosphatase activities in a dose-dependent manner. When an MEK inhibitor was preincubated, insulin failed to stimulate NO production, whereas insulin dramatically increased NO production in the ERK1 overexpressed cells. Taken together, it is proposed that insulin increases iNOS mRNA, iNOS protein, and NO production, possibly via activation of ERK. These may play an important role in osteoblast functions such as collagen synthesis.

Cloning of the histidine biosynthetic genes from Corynebacterium glutamicum: organization and analysis of the hisG and hisE genes.

The physically linked hisG and hisE genes, encoding for ATP-phosphoribosyltransferase and phosphoribosyl-ATP-pyrophosphohydrolase were isolated from the Corynebacterium glutamicum gene library by complementation of Escherichia coli histidine auxotrophs. They are two of the nine genes that participate in the histidine biosynthetic pathway. Molecular genetics and sequencing analysis of the cloned 9-kb insert DNA showed that it carries the hisG and hisE genes. In combining this result with our previous report, we propose that all histidine biosynthetic genes are separated on the genome by three unlinked loci. The coding regions of the hisG and hisE genes are 279 and 87 amino acids in length with a predicted size of about 30 and 10 kDa, respectively. Computer analysis revealed that the amino acid sequences of the hisG and hisE gene products were similar to those of other bacteria.

Identification and characterization of a new member of the placental prolactin-like protein-C (PLP-C) subfamily, PLP-Cbeta.

We have isolated a complementary DNA (cDNA) clone that encodes a new member of the PRL-like protein-C (PLP-C) subfamily of the PRL gene family. The clone was amplified from a 13.5-day-old mouse conceptus cDNA library by PCR using primers based on conserved regions of PLP-C sequences. The full-length cDNA encodes a predicted protein of 241 residues, which contains a putative signal sequence and 2 putative N-linked glycosylation sites. The predicted protein shares 55-66% amino acid identity with mouse PLP-Calpha and rat PLP-D, PLP-H, PLP-Cv, and PLP-C and also contains 6 homologously positioned cysteine residues. Thus, we named this protein PLP-Cbeta for consistency. We have also isolated rat PLP-Cbeta from rat placenta cDNA library. Surprisingly, two messenger RNA (mRNA) isoforms of rat PLP-Cbeta were isolated: one mRNA (rPLP-Cbeta) encodes a 241-amino acid product, but another mRNA (rPLP-Cbetadelta39) lacks 39 bases that encode for a region rich in aromatic amino acids. The 39-bp region corresponds to exon 3 of other PLP-C subfamily members, such as PLP-Calpha, PLP-Cv, and d/tPRP. It suggests that the two isoforms are probably generated by an alternative splicing from a single gene. RT-PCR analysis revealed that the rPLP-Cbeta form was dominantly expressed in placenta, although both isoforms are coexpressed during placentation. The mouse PLP-Cbeta mRNA expression, which was specific to the placenta, was first detected by Northern analysis on embryonic day 11.5 (E 11.5) and persisted until birth. However, in situ hybridization analysis revealed mPLP-Cbeta expression on E 10.5 in specific trophoblast subsets, such as giant cells and spongiotrophoblast cells. mPLP-Cbeta mRNA was detected in the labyrinthine zone on E 18.5, suggesting that spongiotrophoblast cells had penetrated the labyrinthotrophoblast zone. Consistent with the observed expression in trophoblast giant cells, PLP-Cbeta expression was also detected in in vitro differentiated Rcho-1 cells, which express the trophoblast giant cell phenotype. In summary, overall high amino acid identity (79%), the locations of cysteine residues, and consensus sites for N-linked glycosylation between mouse and rat PLP-Cbeta clearly indicate that PLP-Cbeta is a bona fide member of the PLP-C subfamily. The conservation between mouse and rat, the presence of alternative isoforms, and the pattern of expression during gestation suggest the biological significance of PLP-Cbeta during pregnancy.

Role of hsfA gene on host-specificity by Bradyrhizobium japonicum in a broad range of tropical legumes.

Bradyrhizobium japonicum mutant strain NAD163, containing a 30-kb deletion mutant encompassing the hsfA gene, was inoculated onto a broad range of legume species to test host-specificity. Most legume species formed ineffective nodules except Vigna angularis var. Chibopat and Glycine max var. Pureunkong. A hsfA insertion mutant, BjjC211, gave similar results to strain NAD163, implying that many legume species require HsfA for host-specific nitrogen fixation. To determine whether other genes in the deleted region of NAD163 are also necessary, the hsfA gene was conjugally transferred into the NAD163 mutant. The transconjugant formed effective nodules on the host legume plants, which earlier had formed ineffective nodules with mutant NAD163. Thus, we conclude that the hsfA gene in the 30-kb region is the only factor responsible for host-specific nitrogen fixation in legume plants.

Identification and characterization of multiple isoforms of a mouse ribosome receptor.

We isolated multiple cDNA clones encoding various isoforms of a mouse ribosome receptor protein (mRRp). The cDNAs were isolated from a 13.5-day-old mouse conceptus cDNA library by polymerase chain reaction-based screening. The predicted proteins encoded by these cDNAs showed significant homology with ribosome receptors present in dogs (83%), humans (80%), and chickens (45%). The cDNA isoforms had highly identical N- and C-terminal sequences but differed in their central sequences, suggesting that these cDNA isoforms may be derived by alternative splicing from a single gene. Genomic Southern blot analysis confirmed the existence of only a single mouse ribosome receptor gene. Alignments of the deduced amino acid sequences of the mRRp cDNA isoforms revealed that they differ in the number of decapeptide repeats present in the central domain of the protein. These repeats have been previously suggested to mediate ribosome binding and thus differences in repeat number may translate to different ribosome binding abilities. The longest mRRp isoform had 61 tandem repeats. This is of interest because in the human and canine ribosome receptor proteins there are only 54 tandem repeats, suggesting that humans and dogs may also have larger ribosome receptor protein isoforms. Surprisingly, mRRp has a very short basic C-terminal sequence of only 35 amino acids, while in contrast, the known human and canine forms of this protein have acidic C-terminal regions comprised of 803 and 798 amino acid residues, respectively. Although the function of the C-terminal region is currently unknown, it may be that those C-terminal sequences that are present in human and canine RRp proteins but missing in mRRp do not play critical roles in RRp function. The cDNA of the ES/130 isoform, which lacks tandem repeats and presumably are unable to bind ribosomes, could be isolated by reverse transcriptase-PCR from E 13.5 mouse embryos. mRRp mRNAs were expressed in all tissues examined but expression levels of each isoform differed between tissues. The identification of multiple mRRp isoforms in the mouse will allow us to study the regulation and function of ribosome receptors on a genetic level.

Identification and characterization of Psx-2, a novel member of the Psx (placenta-specific homeobox) family.

Psx (now designated as Psx-1) is a murine placenta-specific homeobox gene. Here, we report the isolation and characterization of a second mouse Psx gene (Psx-2). Although 29bp were absent towards the 3' end of Psx-2, Psx-2 and Psx-1 cDNA had identical 5' and 3' ends. Overall sequence identity between the two cDNAs was 91% at the nucleotide level and 81% at the amino acid level. Both Psx proteins contain 227 amino acids. These results suggest that they arose through a recent gene duplication. A surprising finding is that the 81% sequence identity between Psx-1 and Psx-2 proteins drops at the level of homeodomain to 78%. Further, the amino acid at position 51, which is invariably an asparagine in other homeodomains and is known to contact DNA directly, is a methionine in the homeodomains of both Psx-1 and Psx-2. This suggests that Psx proteins may interact with DNA sequences differently to those bound by other homeodomains. Southern blot analysis indicated that the two Psx genes occur on separate loci in the mouse genome. The Psx-2 gene spans approx. 2. 6kb of mouse genome, and contains four exons and three introns.

Psx homeobox gene is X-linked and specifically expressed in trophoblast cells of mouse placenta.

We previously isolated a cDNA clone for a homeobox-containing gene with its expression restricted to the extraembryonic tissues. In this study, Psx gene expression was further examined using in situ hybridization to determine the cellular distribution of Psx transcripts during embryo development. Psx expression was first detected at embryonic day 8.5 only in trophoblast giant cells and chorionic ectoderm. At E 9.5 and E 13.5, the expression was restricted to the giant cells and the labyrinthine trophoblast layer. In addition, the gene expression was detected in differentiated Rcho-1 trophoblast cells in vitro, which is typical of trophoblast giant cells in vivo, but not in proliferating Rcho-1 cells and HRP-1 cells. Interestingly, rat Psx homologue mRNA is about 200 bp shorter than mouse Psx, suggesting that there is a high degree of sequence divergence between the mouse and rat Psx homologues. The sequence divergence, perhaps as a result of rapid evolution, is further supported by the zoo blot analysis because the Psx gene was detectable only in mouse and rat but not in other vertebrate species tested. Psx is localized to the murine X chromosome. Taken together, our results suggest that Psx gene plays a unique role in the function of differentiated trophoblast cells and also serves as a useful model for studying trophoblast cell lineages and the rapid evolution of homeobox genes.