Does Increasing Packing Density Using Larger Caliber Coils Improve Angiographic Results of Embolization of Intracranial Aneurysms at 1 Year: A Randomized Trial.

BACKGROUND AND PURPOSE: The impact of increased aneurysm packing density on angiographic outcomes has not been studied in a randomized trial. We sought to determine the potential for larger caliber coils to achieve higher packing densities and to improve the angiographic results of embolization of intracranial aneurysms at 1 year. MATERIALS AND METHODS: Does Embolization with Larger Coils Lead to Better Treatment of Aneurysms (DELTA) was an investigator-initiated multicenter prospective, parallel, randomized, controlled clinical trial. Patients had 4- to 12-mm unruptured aneurysms. Treatment allocation to either 15- (experimental) or 10-caliber coils (control group) was randomized 1:1 using a Web-based platform. The primary efficacy outcome was a major recurrence or a residual aneurysm at follow-up angiography at 12 ± 2 months adjudicated by an independent core lab blinded to the treatment allocation. Secondary outcomes included indices of treatment success and standard safety outcomes. Recruitment of 564 patients was judged necessary to show a decrease in poor outcomes from 33% to 20% with 15-caliber coils. RESULTS: Funding was interrupted and the trial was stopped after 210 patients were recruited between November 2013 and June 2017. On an intent-to-treat analysis, the primary outcome was reached in 37 patients allocated to 15-caliber coils and 36 patients allocated to 10-caliber coils (OR = 0.931; 95% CI, 0.528-1.644; P = .885). Safety and other clinical outcomes were similar. The 15-caliber coil group had a higher mean packing density (37.0% versus 26.9%, P = .0001). Packing density had no effect on the primary outcome when adjusted for initial angiographic results (OR = 1.001; 95% CI, 0.981-1.022; P = .879). CONCLUSIONS: Coiling of aneurysms randomized to 15-caliber coils achieved higher packing densities compared with 10-caliber coils, but this had no impact on the angiographic outcomes at 1 year, which were primarily driven by aneurysm size and initial angiographic results.

Lutetium-177-labelled anti-prostate-specific membrane antigen antibody and ligands for the treatment of metastatic castrate-resistant prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Promising therapeutic results of the prostate-specific membrane antigen (PSMA) ligand have been shown when labelling with lutetium-177 (177Lu). We performed a systematic review and meta-analysis to assess the therapeutic response of 177Lu-PSMA in the treatment of metastatic castration-resistant prostate cancer (mCRPC). METHODS: A systematic review was conducted using electronic databases up to December 2016. Two reviewers independently extracted data and assessed methodological quality. The main outcome of interest was antitumour biochemical response of 177Lu-PSMA, analysing two measures: 'any PSA decline' and '>50% decline' from baseline. A random-effects meta-analysis was used to calculate the pooled proportion across studies. The I2 statistic was calculated in each case to investigate the extent of heterogeneity across the studies. A sensitivity analysis was conducted removing two studies, which were presented as abstracts and proportions were summarised by chemical type (177Lu-J591/DKZ/I&T). All analyses were conducted using Stata v14. RESULTS: A total of 10 studies were included in the analysis giving a total sample size of 369, 220 (of 334 analysable) experienced any PSA decline. The pooled proportion of patients with any PSA decline was 68% (95% confidence interval (CI): 61-74). The I2 statistic was 39.1% (P=0.11) suggesting minor heterogeneity between results. The pooled proportion of patients with >50% PSA decline was 37% (95% CI: 22-52). The I2 statistic was 91.0% (P<0.001) suggesting substantial heterogeneity between results. On subgroup analysis, a higher proportion of patients in the 177Lu-DKZ/I&T subgroup had a PSA decline >50%, however, it can be seen that the 177Lu-DKZ/I&T subgroup had a substantial amount of heterogeneity across studies. CONCLUSIONS: This review suggests promising early results for the treatment of mCRPC, especially from patients treated with the more recently developed radioligands. Overall, our meta-analysis showed that approximately two-thirds of patients had a biochemical response. Randomised-controlled trials would be necessary to verify its effectiveness against current systemic therapies and create an ideal treatment protocol.

Systematic review and meta-analysis on management of acute urinary retention.

BACKGROUND: Acute urinary retention (AUR) is a common urological emergency. In this article, we review the current literature and present a structured summary in management of AUR. METHODS: A systematic review was conducted using the keywords 'acute AND retention AND urin*' within the title in search engines including Medline, EMBASE and EBM Review. The obtained literature was manually reviewed by the primary author (PDY) and was further refined by confining the subject to management of AUR. Exclusion criteria included paediatric and female population studies, case reports, reviews, surveys, economical assessment and articles on AUR in prostate cancer and post-operative patients. RESULTS: Total of 54 articles met our inclusion and exclusion criteria. The trial without catheter (TWOC) post-immediate catheterisation is widely practiced although there remains a significant variability in terms of type and duration of catheterisation required, use of concurrent medical therapy or post-catheterisation management. Our systematic review and subsequent meta-analysis has shown superiority of α1-adrenergic receptor blockers over placebo in achieving successful voiding in patients with AUR. Suprapubic catheter (SPC) is an alternative to urethral catheterisation (indwelling catheter (IDC)) and may provide several advantages. Clean intermittent self-catheterisation may be a safe and useful option for patients with AUR until their definitive management. The overall long-term outcome of in-and-out catheterisation remains promising in selected patients. Surgery is an end point in patients with unsuccessful TWOC as well as in those with significant lower urinary tract symptoms post-successful TWOC. CONCLUSIONS: We recommend use of α1-adrenergic receptor blockers before TWOC and discourage emergency operative management. Use of SPC over IDC in AUR is debatable. Duration of catheterisation is controversial but <3 days is a safe option in avoiding catheterisation-related complications. Although TURP remains the current gold standard, there has been an emergence of newer operative management utilising laser techniques.

Prostate cancer: measuring PSA.

Population screening with prostate-specific antigen (PSA) for detection of prostate cancer is a topic associated with ongoing dissent and confusion within the oncology and wider medical community. The PSA blood test has been used in various stages of prostate cancer management, including screening and the assessment of future risk of prostate cancer development, detection of recurrent disease after local therapy and in the management of advanced disease. However, PSA-based decision-making in prostate cancer has significant shortcomings. This review will summarise the evidence and current recommendations for the use of PSA in detection and management of prostate cancer.

Do screening trial recruitment logs accurately reflect the eligibility criteria of a given clinical trial? Early lessons from the RAVES 0803 trial.

AIMS: Maintaining clinical trial screening logs and reporting data from such logs are given importance due to the relevance of a trial's patient population to the generalisability of its findings. However, screening logs may not always reflect a clinical trial's true target population. The aim of the present study was to define and compare 'apparent recruitment' to a trial as captured in a clinical trial screening log with 'true recruitment', which considers all potentially eligible patients. The Trans Tasman Radiation Oncology Group (TROG) 0803 RAVES clinical trial was used to examine the above. MATERIALS AND METHODS: A prospective, surgical database was interrogated for the 12 month period to identify patients potentially eligible for the TROG 0803 RAVES trial. Information on whether patients were referred to a RAVES trial recruitment site and reasons for non-referral were obtained. RESULTS: Of 92 men undergoing radical prostatectomy, 28 met the RAVES clinical trial eligibility criteria. Fifteen of the 28 eligible men were assessed at a RAVES trial site, with five being ultimately recruited to RAVES (33% 'apparent recruitment fraction' as captured by the site's trial screening log). The 'true recruitment fraction' was 5/28 (18%). CONCLUSION: Screening logs at a recruiting trial site may underestimate the trial's target population and overestimate recruitment. Only a subpopulation of all eligible patients may be captured in trial screening logs and subsequently reported on. This may affect the generalisability of the trial's reported findings.

Long-term followup after electrocautery transurethral resection of the prostate for benign prostatic hyperplasia.

Introduction. For decades, transurethral resection of the prostate (TURP) has been the "gold standard" operation for benign prostatic hyperplasia (BPH) but is based mainly on historic data. The historic data lacks use of validated measures and current TURP differs significantly from that performed 30 years ago. Methods. Men who had undergone TURP between 2001 and 2005 were reviewed. International prostate symptom score (IPSS), quality of life (QOL) and peak urinary flow rate (Q(max⁡)), and postvoid residual (PVR) were recorded. Operative details and postoperative complications were documented. Patients were then invited to attend for repeat assessment. Results. 91 patients participated. Mean follow-up time was 70 months. Mean follow-up results were IPSS-7; QoL-1.5; Q(max⁡)-23 mL/s; PVR-45 mL. These were an improvement from baseline of 67%, 63%, 187%, and 80%, respectively. Early complication rates were low, with no blood transfusions, TUR syndrome, or deaths occurring. Urethral stricture rate was higher than anticipated at 14%. Conclusion. This study shows modern TURP still produces durable improvement in voiding symptoms which remains comparable with historic studies. This study, however, found a marked drop in early complications but, conversely, a higher than expected incidence of urethral strictures.

Very late thrombosis of flow-diverting constructs after the treatment of large fusiform posterior circulation aneurysms.

BACKGROUND AND PURPOSE: The PED is a new endoluminal construct designed to exclude aneurysms from the parent cerebrovasculature. We report the very late (>1 year) thrombosis of PED constructs in 2 patients. RESULTS: Two patients with very large fusiform basilar trunk aneurysms underwent parent artery reconstruction with the PED. Both patients were maintained on dual antiplatelet therapy throughout the first year following treatment. Follow-up conventional angiography, performed 12 months after treatment, demonstrated, in both patients, thrombosis of most of the aneurysm with minimal residual flow through the construct and into the aneurysm fundus. In response to the residual filling, clopidogrel was discontinued (aspirin therapy was maintained). Both patients presented with symptomatic acute occlusions of the PED constructs within 14 days of clopidogrel discontinuation. DISCUSSION: Patient 1 presented with constitutional symptoms that progressed to severe headache without other neurologic signs or symptoms. Occlusion of the PED construct was confirmed with conventional angiography. MR imaging demonstrated no evidence of infarction or parenchymal injury. The headaches were managed successfully with steroid therapy. Patient 2 presented with a syndrome of acute basilar occlusion with brain stem stroke. Complete occlusion was confirmed on angiography. Emergent thrombolysis with mechanical revascularization was performed successfully; however, the patient ultimately succumbed to the infarction. CONCLUSIONS: It appears that flow-diverting constructs built across large circumferential aneurysms may remain thrombogenic for much longer than conventional intracranial or peripheral bare metal stents. Constructs in these patients may remain susceptible to very late thrombosis, >1 year after implantation. These patients likely require long-term dual antiplatelet therapy (>1 year) to provide adequate prophylaxis against thrombosis. If these types of aneurysms demonstrate persistent residual filling months after PED reconstruction, operators should consider the placement of additional devices as an alternative to the discontinuation of 1 of the antiplatelet medications.

Regulation of non-AU-rich element containing c-fms proto-oncogene expression by HuR in breast cancer.

The role of RNA-binding proteins in cancer biology is recognized increasingly. The nucleocytoplasmic shuttling and AU-rich RNA-binding protein HuR stabilizes several cancer-related target mRNAs. The proto-oncogene c-fms, whose 3'untranslated region (3'UTR) is not AU-rich, is associated with poor prognosis in breast cancer. Using a large breast-cancer tissue array (N=670), we found nuclear HuR expression to be associated with nodal metastasis and independently with poor survival (P=0.03, RR 1.45), as well as to be co-expressed with c-fms in the breast tumors (P=0.0007). We described c-fms mRNA as a direct target of HuR in vivo, and that HuR bound specifically to a 69-nt region containing 'CUU' motifs in 3'UTR c-fms RNA. Overexpressing or silencing HuR significantly up- or down-regulated c-fms RNA expression, respectively. We also found that known glucocorticoid stimulation of c-fms RNA and protein is largely dependent on the presence of HuR. HuR, by binding to the 69-nt wild type, but not mutant, c-fms sequence can regulate reporter gene expression post-transcriptionally. We are the first to describe that HuR can regulate gene expression by binding non-AU-rich sequences in 3'UTR c-fms RNA. Collectively, our findings suggest that HuR plays a supportive role for c-fms in breast cancer progression by binding a 69-nt element in its 3'UTR, thus regulating its expression.

Balloon assisted treatment of intracranial aneurysms: the conglomerate coil mass technique.

Endovascular techniques for the treatment of intracranial aneurysms have rapidly evolved over the past 15 years since the introduction and subsequent US Food and Drug administration approval of the Gugleilmi detachable coil. During this period, a number of different coil designs and adjunctive devices have been developed to facilitate the treatment of more complex and challenging cerebral aneurysms. One such adjunctive device, the hypercompliant occlusion balloon, can be temporarily inflated during the delivery of embolization coils to prevent their prolapse into the parent vessel. This technique, known as balloon assisted treatment (BAT), remains somewhat controversial as many operators do not incorporate this approach into their practice, favoring stent supported techniques instead. Moreover, those operators who do practice BAT use a variety of different approaches. In this review, we discuss the theoretical concepts underlying BAT, the potential advantages and disadvantages of this approach and finally the technical evolution of BAT in our endovascular practice.

Self-expanding stents for recanalization of acute cerebrovascular occlusions.

BACKGROUND AND PURPOSE: Stent-assisted revascularization increases prevailing recanalization rates ( congruent with 50%-69%) for vessel occlusions recalcitrant to thrombolytics. Although balloon-mounted coronary stents can displace thrombus (via angioplasty) and retain clot along vessel walls, intracranial self-expanding stents are more flexible and exert less radial outward force during deployment, increasing deliverability and safety. To understand the effectiveness of self-expanding stents for recanalization of acute cerebrovascular occlusions, we retrospectively reviewed our preliminary experience with these stents. MATERIALS AND METHODS: Eighteen patients (19 lesions) presenting with a clinical diagnosis of acute stroke underwent catheter-based angiography documenting focal occlusion of an intracranial artery. A self-expanding stent was delivered to the occlusion and deployed. Stent placement was the initial mechanical maneuver in 6 cases; others involved a combination of pharmacologic and/or mechanical maneuvers prestenting. GP IIb/IIIa inhibitors were administered in 10 cases intraprocedurally or immediately postprocedurally to avoid acute in-stent thrombosis. RESULTS: Stent deployment at the target occlusion (technical success) was achieved in all cases. Thrombolysis in Cerebral Ischemia (TICI)/Thrombolysis in Myocardial Ischemia (TIMI) 2/3 recanalization (angiographic success) was achieved in 15 of 19 lesions (79%). All single-vessel lesions (n=8) were recanalized, but only 7 of 11 combination internal carotid artery and middle cerebral artery lesions were recanalized. No intraprocedural complications occurred. Seven in-hospital deaths occurred: stroke progression, 4; intracranial hemorrhage, 2; respiratory failure, 1. Seven patients had >or=4-point National Institutes of Health Stroke Scale improvement within 24 hours after the procedure, 6 had modified Rankin Score (mRS)

Rapid intracranial clot removal with a new device: the alligator retriever.

BACKGROUND AND PURPOSE: Despite availability of an approved drug to treat acute cerebral ischemia, most patients with stroke do not realize a good outcome. A method that would rapidly increase or restore cerebral perfusion before irreversible cell death should improve patient outcomes. MATERIALS AND METHODS: We recently had the opportunity to treat 6 middle-aged-to-elderly patients who presented with signs and symptoms of acute cerebral ischemia, by mechanically removing their (predominantly) middle cerebral artery clots by using a new retrieval device that had been previously approved by the US Food and Drug Administration for intravascular retrieval of foreign bodies. During a 2-month period, the 6 patients were treated in 5 separate institutions. No patient had an unsuccessful attempt at clot removal. The cases were collected by personal communication with each operator. RESULTS: In all instances, use of the device resulted in rapid clot removal. Each patient had a large improvement in National Institutes of Health Stroke Scale score. Two of the 6 patients had experienced failure of another clot retrieval device, and 3 patients required no systemic thrombolytics, reducing the likelihood of one of the most feared complications of stroke therapy, intracranial hemorrhage. SUMMARY: We believe that use of this device may result in improved outcomes for patients with acute ischemic stroke. In our limited experience, it provided a rapid, safe, and effective means for achieving revascularization.

Altered susceptibility to infection by Sinorhizobium meliloti and Nectria haematococca in alfalfa roots with altered cell cycle.

Most infections of plant roots are initiated in the region of elongation; the mechanism for this tissue-specific localization pattern is unknown. In alfalfa expressing PsUGT1 antisense mRNA under the control of the cauliflower mosaic virus (CaMV) 35S promoter, the cell cycle in roots is completed in 48 h instead of 24 h, and border cell number is decreased by more than 99%. These plants were found to exhibit increased root-tip infection by a fungal pathogen and reduced nodule formation by a bacterial symbiont. Thus, the frequency of infection in the region of elongation by Nectria haematocca was unaffected, but infection of the root tip was increased by more than 90%; early stages of Sinorhizobium meliloti infection and nodule morphology were normal, but the frequency of nodulation was fourfold lower than in wild-type roots.

Transarterial Wedged-catheter, Flow-arrest, N-butyl Cyanoacrylate Embolization of Three Dural Arteriovenous Fistulae in a Single Patient.

SUMMARY: The pathogenesis of dural arteriovenous fistulas (DAVFs) is currently unknown, with multiple DAVFs being rare. For patients with limited venous access secondary to sinus thrombosis, or for patients where parent sinus occlusion would not be tolerated, transvenous embolization may not be possible and other treatment methods must be considered. A 69-year-old female patient with a two-year history of progressive headaches, memory loss, and unsteady gait underwent cerebral angiography that revealed three separate DAVFs with congested cortical venous drainage overlying both frontal lobes. Using an application of a transarterial wedged-catheter, flow-arrest technique, N-butyl cyanoacrylate was deposited across all three pathologic arteriovenous connections providing a definitive cure. Transarterial NBCA embolization may provide curative treatment of DAVFs, and is of particular utility in situations where access to the draining venous structures is limited.

Single foetal death in twin pregnancies: review of the maternal and neonatal outcomes and management.

OBJECTIVE: To review the maternal and neonatal outcomes, and management of single foetal death in twin pregnancies. DATA SOURCES: Medline literature search (1950 to 1999) and hospital audit of single antepartum foetal deaths in twin pregnancy from 1993 through 1997. DATA SELECTION: Key words for literature search: twin pregnancy/pregnancies; single fetal death/demise. DATA EXTRACTION: Data were extracted and reviewed independently by the authors. DATA SYNTHESIS: During the study period, 182 (0.76%) of 23,804 deliveries involved twin pregnancies. Seven (3.8%) of the twin pregnancies were complicated by the death of one foetus. Single foetal death in a twin pregnancy in the late second and third trimesters is associated with significant morbidity and mortality in the surviving co-twin, especially in a pregnancy involving monochorionic twins. Management should be individualised; conservative management is preferred by most obstetricians. CONCLUSION: Single foetal death in twin pregnancies should be managed in a tertiary referral centre, where intensive foetal surveillance and adequate neonatal support are available. A multidisciplinary approach should be adopted.

Urodynamic assessment of the bashful bladder.

PURPOSE: We prospectively studied the potential contribution of ambulatory urodynamic monitoring in men with urinary symptoms unable to initiate a void on conventional video cystometrography. MATERIALS AND METHODS: A total of 40 consecutive symptomatic men with a median International Prostate Symptom Score of 19 (range 1 to 29) and median age of 51.9 years (range 30 to 75) who were unable to void during video cystometrography underwent ambulatory urodynamic monitoring. Solid-state transducers mounted on silicone coated catheters were inserted urethrally and rectally, and connected to a portable recorder. Subjects voided in private into a specially designed flow meter, which they connected to the recording device. RESULTS: Of the patients 2 (5%) failed to attend ambulatory urodynamic monitoring, despite multiple reminders, and in 1 (2.5%) the trace was uninterpretable. Pressure flow data were available for the remaining 37 patients with mean plus or minus standard deviation 2.72+/-0.1 storage void cycles recorded per patient. All 6 patients (15%) with obstruction were older than 40 years. In 6 cases (15%) obstruction was equivocal and the remainder were unobstructed. Transurethral prostatic resection in 2 and urethrotomy in 1 of 6 patients with obstruction resulted in subjective and objective improvement. CONCLUSIONS: The bashful bladder syndrome was not associated with any specific urodynamic diagnosis. Ambulatory urodynamic monitoring will yield a urodynamic diagnosis in more than 90% of cases after failure to record void data on video cystometrography. A surgically correctable cause of symptoms can be found in about 20% of men older than 40 years. The contribution of ambulatory urodynamic monitoring compared to more conventional evaluation in men younger than 40 years is negligible.

Meristem-localized inducible expression of a UDP-glycosyltransferase gene is essential for growth and development in pea and alfalfa.

PsUGT1, which encodes a microsomal UDP-glucuronosyltransferase, was cloned from root tips of Pisum sativum. PsUGT1 expression is correlated with mitosis and strongly induced in dividing cells. A region at the C terminus of the encoded protein is closely related to the UDP-glucuronic acid binding site consensus sequence, and the protein encoded by PsUGT1 catalyzes conjugation of UDP-glucuronic acid to an unknown compound. Overexpression of PsUGT1 sense mRNA has no detectable effect on transgenic pea hairy root cultures or regenerated alfalfa. However, inhibiting PsUGT1 expression by the constitutive expression of antisense mRNA (under the control of the cauliflower mosaic virus 35S promoter) markedly retards growth and development of transgenic alfalfa. Cell structure and organization in the antisense plants are similar to those of controls, but plant growth is reduced and development is delayed. This inhibition in growth is correlated with a twofold delay in the time required for completion of a cell cycle and with a >99% inhibition of border cell production. Inhibition of PsUGT1 expression by meristem-localized inducible expression of PsUGT1 antisense mRNA (under the control of its own promoter) is lethal both in pea hairy roots and in transgenic alfalfa plants. These results indicate that PsUGT1 expression is required for normal plant growth and development, and they are consistent with the hypothesis that this UDP-glycosyltransferase regulates activity of a ligand(s) needed for cell division.

Contemporary management of spinal osteomyelitis.

OBJECTIVE: We review the results of treatment of a series of patients with spinal osteomyelitis, to formulate a systematic and comprehensive approach to the management of this disease in light of recent technical and conceptual advances in imaging, spinal biomechanics, and internal fixation. METHODS: We retrospectively reviewed the records for 57 consecutive patients with pyogenic spinal osteomyelitis who were treated between June 1987 and June 1995. Pain and weakness were the most common presenting symptoms. The mean duration of symptoms at the time of diagnosis was 10.6 weeks. Surgical indications included the presence or development of motor deficits with epidural compression and/or localized kyphotic deformities or the failure of medical therapy. RESULTS: Thirty-three patients underwent surgery as their initial treatment. Six additional patients experienced medical therapy failure and received subsequent surgical treatment. Seventeen patients were treated using an anterior approach only, 13 were treated using a posterior approach only, and 9 were treated using a combined anterior and posterior approach. After a minimal follow-up period of 24 months, 93% of the surgically treated patients showed neurological improvement or were neurologically intact, with a mean 16-degree decrease in localized kyphotic deformities and with solid bony fusion and resolution of pain for all patients. CONCLUSION: Early surgical decompression results in rapid improvement of neurological deficits, decreases in kyphotic deformities, and stabilization with bony fusion. The presence of active infection does not preclude the use of internal fixation. Nonsurgical management is indicated for patients with minimal or no neurological deficits and the absence of significant localized kyphotic deformities. However, 25% of patients who were initially treated nonsurgically experienced medical therapy failure and underwent surgical treatment.

Function of root border cells in plant health: pioneers in the rhizosphere.

Plants dedicate a large amount of energy to the regulated production of living cells programmed to separate from roots into the external environment. This unusual process may be worth the cost because it enables the plant to dictate which species will share its ecological niche. For example, border cells can rapidly attract and stimulate growth in some microorganisms and repel and inhibit the growth of others. Such specificity may provide a way to control the dynamics of adjacent microbial populations in the soil to foster beneficial associations and inhibit pathogenic invasion. Plant genes controlling the delivery of border cells and the expression of their unique properties provide tools to genetically engineer plants with altered border cell quality and quantity. Such variants are being used to test the hypothesis that the function of border cells is to protect plant health by controlling the ecology of the root system.