A Pragmatic Randomized Trial Comparing Surgical Clipping and Endovascular Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Surgical clipping and endovascular treatment are commonly used in patients with unruptured intracranial aneurysms. We compared the safety and efficacy of the 2 treatments in a randomized trial. MATERIALS AND METHODS: Clipping or endovascular treatments were randomly allocated to patients with one or more 3- to 25-mm unruptured intracranial aneurysms judged treatable both ways by participating physicians. The study hypothesized that clipping would decrease the incidence of treatment failure from 13% to 4%, a composite primary outcome defined as failure of aneurysm occlusion, intracranial hemorrhage during follow-up, or residual aneurysms at 1 year, as adjudicated by a core lab. Safety outcomes included new neurologic deficits following treatment, hospitalization of >5 days, and overall morbidity and mortality (mRS > 2) at 1 year. There was no blinding. RESULTS: Two hundred ninety-one patients were enrolled from 2010 to 2020 in 7 centers. The 1-year primary outcome, ascertainable in 290/291 (99%) patients, was reached in 13/142 (9%; 95% CI, 5%-15%) patients allocated to surgery and in 28/148 (19%; 95% CI, 13%-26%) patients allocated to endovascular treatments (relative risk: 2.07; 95% CI, 1.12-3.83; P = .021). Morbidity and mortality (mRS >2) at 1 year occurred in 3/143 and 3/148 (2%; 95% CI, 1%-6%) patients allocated to surgery and endovascular treatments, respectively. Neurologic deficits (32/143, 22%; 95% CI, 16%-30% versus 19/148, 12%; 95% CI, 8%-19%; relative risk: 1.74; 95% CI, 1.04-2.92; P = .04) and hospitalizations beyond 5 days (69/143, 48%; 95% CI, 40%-56% versus 12/148, 8%; 95% CI, 5%-14%; relative risk: 0.18; 95% CI, 0.11-0.31; P < .001) were more frequent after surgery. CONCLUSIONS: Surgical clipping is more effective than endovascular treatment of unruptured intracranial aneurysms in terms of the frequency of the primary outcome of treatment failure. Results were mainly driven by angiographic results at 1 year.

Outcomes of Kidney Transplant During the SARS-CoV-2 Pandemic at 1 Center in Poland.

The SARS-CoV-2 pandemic has significantly affected the number of transplanted organs worldwide. The rules and restrictions related to transplantation activities in Poland are included in the updated guidelines of the Polish Organizational and Coordination Centre for Transplantation. Our clinic faces the same problems as the rest of the hospitals in the country. Not only are the number of recipients falling, but there are also numerous restrictions concerning, among other things, qualification of donors and recipients and even preparation of centers for long-term care in the event of infection of organ recipients with the SARS-CoV-2 virus. Statistics showed, after an initial fall in the number of kidneys transplanted, a temporary normalization during the summer months, only to record a fall again with an increase in new cases of COVID-19. A total of 29 kidneys were transplanted at our center between March and December 2020. Kidney transplantation is not only linked to the operation itself, but also to the follow-up care of the recipients. Reduced immunity among recipients due to immunosuppressive treatment as well as comorbidities among recipients contribute to this group being at increased risk of symptomatic SARS-CoV-2 infection. The number of cases of SARS-CoV-2 infection among kidney transplant recipients at our center was 7, of which we recorded 2 deaths due to COVID-19 in the period after kidney transplant. Postoperative complications probably related to previous SARS-CoV-2 infection occurred in 1 patient.

The Arterial Anastomosis Between Deep Inferior Epigastric Artery and Small Polar Renal Artery in Kidney Transplantation: A Case Report.

The presence of multiple renal arteries is the most common form of vascular anomalies found in donor kidneys. In rare cases, small renal polar arteries may be found. They can be anastomosed with deep inferior epigastric arteries, resulting in vascular augmentation of transplanted kidneys and contributing to better graft function. Renal perfusion may be increased via 2 types of vascular reconstruction known as "turbocharging" and "supercharging". Turbocharging uses vascular sources within the same organ area, whereas supercharging uses distant vascular sources. Using additional vessels can either complicate the surgery or, contradictorily, ease the way of procedure. This case study presents a kidney transplant during which arterial anastomosis between deep inferior epigastric artery and small polar renal artery was performed.

Noninvasive Angiographic Results of Clipped or Coiled Intracranial Aneurysms: An Inter- and Intraobserver Reliability Study.

BACKGROUND AND PURPOSE: Noninvasive angiography is commonly used to assess the outcome of surgical or endovascular treatment of intracranial aneurysms in clinical series or randomized trials. We sought to assess whether a standardized 3-grade classification system could be reliably used to compare the CTA and MRA results of both treatments. MATERIALS AND METHODS: An electronic portfolio composed of CTAs of 30 clipped and MRAs of 30 coiled aneurysms was independently evaluated by 24 raters of diverse experience and training backgrounds. Twenty raters performed a second evaluation 1 month later. Raters were asked which angiographic grade and management decision (retreatment; close or long-term follow-up) would be most appropriate for each case. Agreement was analyzed using the Krippendorff α (αK) statistic, and the relationship between angiographic grade and clinical management choice, using the Fisher exact and Cramer V tests. RESULTS: Interrater agreement was substantial (αK = 0.63; 95% CI, 0.55-0.70); results were slightly better for MRA results of coiling (αK = 0.69; 95% CI, 0.56-0.76) than for CTA results of clipping (αK = 0.58; 95% CI, 0.44-0.69). Intrarater agreement was substantial to almost perfect. Interrater agreement regarding clinical management was moderate for both clipped (αK = 0.49; 95% CI, 0.32-0.61) and coiled subgroups (αK = 0.47; 95% CI, 0.34-0.54). The choice of clinical management was strongly associated with the size of the residuum (mean Cramer V = 0.77 [SD, 0.14]), but complete occlusions (grade 1) were followed more closely after coiling than after clipping (P = .01). CONCLUSIONS: A standardized 3-grade scale was found to be a reliable and clinically meaningful tool to compare the results of clipping and coiling of aneurysms using CTA or MRA.

Transplantation of a Kidney With Duplicated Ureter Harvested From a Donor With Vascular Anomaly in the Form of Double Inferior Vena Cava: A Case Report.

During the organ procurement procedure, a surgeon encounters anatomic anomalies not very often but also not uncommonly. These changes may put the success of the transplant into question. Despite the thorough diagnosis of the potential donor, these anomalies are often diagnosed during organ donation. In our paper we present a case of kidney transplantation with duplicated ureter. The organ was collected from a donor with duplicated inferior vena cava. After transplantation, the kidney functioned immediately. Taking into consideration the well-being of the recipient, organs with anatomic abnormalities should be carefully considered for transplantation. This is especially important when there is a constant shortage of organs for transplantation.

Reliability of CT Angiography in Cerebral Vasospasm: A Systematic Review of the Literature and an Inter- and Intraobserver Study.

BACKGROUND AND PURPOSE: Computed tomography angiography offers a non-invasive alternative to DSA for the assessment of cerebral vasospasm following subarachnoid hemorrhage but there is limited evidence regarding its reliability. Our aim was to perform a systematic review (Part I) and to assess (Part II) the inter- and intraobserver reliability of CTA in the diagnosis of cerebral vasospasm. MATERIALS AND METHODS: In Part I, articles reporting the reliability of CTA up to May 2018 were systematically searched and evaluated. In Part II, 11 raters independently graded 17 arterial segments in each of 50 patients with SAH for the presence of vasospasm using a 4-category scale. Raters were additionally asked to judge the presence of any moderate/severe vasospasm (≥ 50% narrowing) and whether findings would justify augmentation of medical treatment or conventional angiography ± balloon angioplasty. Four raters took part in the intraobserver reliability study. RESULTS: In Part I, the systematic review revealed few studies with heterogeneous vasospasm definitions. In Part II, we found interrater reliability to be moderate at best (κ ≤ 0.6), even when results were stratified according to specialty and experience. Intrarater reliability was substantial (κ > 0.6) in 3/4 readers. In the per arterial segment analysis, substantial agreement was reached only for the middle cerebral arteries, and only when senior raters' judgments were dichotomized (presence or absence of ≥50% narrowing). Agreement on the medical or angiographic management of vasospasm based on CTA alone was less than substantial (κ ≤ 0.6). CONCLUSIONS: The diagnosis of vasospasm using CTA alone was not sufficiently repeatable among observers to support its general use to guide decisions in the clinical management of patients with SAH.

A randomized trial of endovascular versus surgical management of ruptured intracranial aneurysms: Interim results from ISAT2.

BACKGROUND AND PURPOSE: Appropriate management of ruptured intracranial aneurysm (RIA) in patients eligible for surgical clipping but under-represented in or excluded from previous randomized trials remains undetermined. METHODS: The International Subarachnoid Aneurysm Trial-2 (ISAT-2) is a randomized care trial comparing surgical versus endovascular treatment (EVT) of RIA. All patients considered for surgical clipping but eligible for endovascular treatment can be included. The primary endpoint is death or dependency on modified Rankin score (mRS>2) at 1 year. Secondary endpoints are 1 year angiographic results and length of hospital stay. RESULTS: An interim analysis was performed after 103 patients were treated from November 2012 to July 2017 in 4 active centers. Fifty-two of the 55 patients allocated to surgery were treated by clipping, and 45 of the 48 allocated to EVT were treated by coiling, with 3 crossovers in each arm. The main endpoint (1 year mRS>2), available for 76 patients, was reached in 16/42 patients allocated to clipping (38%; 95%CI: 25%-53%), and 10/34 patients allocated to coiling (29%; 17%-46%). One year imaging results were available in 54 patients: complete aneurysm occlusion was found in 23/27 patients allocated to clipping (85%; 67%-94%), and 18/27 patients allocated to coiling (67%; 47%-81%). Hospital stay exceeding 20 days was more frequent in surgery (26/55 [47%; 34%-60%]) than EVT (9/48 [19%; 10%-31%]). CONCLUSION: Ruptured aneurysm patients for whom surgical clipping may still be best can be managed in a randomized care trial, which is feasible in some centers. More participating centers are needed.

Correlation Between Percentage of Immuncompetent CD4+ and CD4+CD25+ Cells and Compatibility in the HLA System and Selected Parameters Assessing Transplanted Kidney Function.

BACKGROUND: Long-term kidney allograft survival is affected by many coexisting immunologic factors. Currently, only two basic immunologic parameters-HLA compatibility and panel reactive antibodies-are routinely used in kidney transplantation management. At the same time, there is a great need for immunologic biomarkers that will help inrease understanding of kidney transplant immunology and improve clinical care of kidney recipients. T regulatory cells (Tregs) represent one of the major targets of this approach. The aim of this study was to investigate possible simple associations between Tregs count in recipients' blood and other routinely assessed or easily accessible laboratory parameters. METHODS: Laboratory outcomes from medical files of transplant outpatient clinic in combination with flow cytometry analyses of particular immunocompetent cells populations were used. Flow cytometry was used to calculate Tregs recognized as TCD4+CD25high. The Spearman rank correlation test was used to verify particular associations. RESULTS: A negative correlation was found beween HLA compatibility and Tregs count as well as between platelets count and Tregs count. CONCLUSIONS: Whereas the negative correlation between Tregs and platelets counts may possibly mirror some recent findings in basic research, a negative correlation between HLA compatibility and Tregs points the direction of further research to factors triggering post-transplant immune tolerance.

The Importance of New Generation Sequencing (NGS) HLA Typing in Renal Transplantation-Preliminary Report.

INTRODUCTION: Thanks to new generation sequencing (NGS) and expansion of HLA typing with additional loci, it will be possible to increase the effectiveness of graft survival and to avoid complications related to the immune system. New pharmacogenetic factors are still being researched to develop better immunosuppressive treatment. MATERIAL AND METHODS: The incidence of polymorphic HLA loci variants was established, based on a high-resolution NGS method in kidney graft recipients. Furthermore, haplotypic analysis between examined loci was conducted to type additional loci that may influence the transplantation result. A total of 120 kidney recipients were enrolled in the study. A commercial DNA extraction kit in Tubes (QIAamp DNA Blood Mini Kit Qiagen, Germany) was used to isolate DNA from the blood. Sequencing library preparation was done with TruSight HLA set. The Conexio computer program was used to analyse the results of HLA typing. RESULTS: The patients with alleles A*02:01:01, B*44:02:01, C*03:03:01, C*01:02:01, C*05:01:01, C*07:02:01, DQB1*03:03:02, DQB1*06:04:01, or with haplotypic variation A*25:01:01-B*18:01:01- C*15:01:01 were taking the highest doses of cyclosporine (CsA), in contrast to patients with allele B*18:01:01, DQB1*06:02:01, DQB1*02:02:01, or haplotypic variation A*02:01:01- B*44:02:01-C*01:01:01, who were taking the lowest doses. The highest dose of tacrolimus (TAC) was administered to patients with alleles A*68:01:02, A*29:01:01, B*07:02:01, B*35:02:01, B*38:01:01, DRB1*12:01:01, DQB1*05:03:01, or haplotypic variations A*02:01:01-B*57:01:01-C*07:01:01, A*03:01:01-B*07:02:01-C*13:01:01, A*29:02:01-B*44:03:01- C*07:01:01, and A*01:01:01-B*08:01:01-C*03:01:01. Additionally, it was established that HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DPA1, and HLA-DQA1 show very slight polymorphism, which suggests that there is no need for their typing for transplantation purposes. Moreover, loci HLA-C, HLA-DQB1, and HLA-DPB1, which are not routinely examined in recipient-donor matching, show genetic variability that may increase the risk of transplant rejection or shortened graft life. CONCLUSIONS: Expanding the qualification procedure to include allele genotyping could allow clinicians to establish immunosuppressive treatment schemes that would be optimally suited for recipients' phenotype.

Autologous cord blood transfusion in preterm infants - could its humoral effect be the kez to control prematurity-related complications? A preliminary study.

Umbilical cord blood (UCB), rich in stem/progenitor cells, is partially eliminated from the bloodstream during childbirth because the cord is immediately clamped. We hypothesize that transfusion of autologous UCB to premature infants after delivery could serve as an adjuvant modality for preventing the development of prematurity-related complications. We randomly enrolled 20 preterm infants born before 32 weeks of gestational age (GA), all of whom developed anemia, necessitating transfusion of red blood cells (RBCs). Two groups, matched for GA, were selected: (1) infants (n = 5) who underwent UCB transfusion once within 5 days of birth (mean ± standard deviation, 3.2 ± 1.9 days) and (2) infants (n = 15) from whom UCB was not collected (e.g., lack of consent). The latter served as controls and received allogeneic RBC transfusions (7.8 ± 3.9 days after birth). Selected prematurity-related complications were monitored. Two weeks after UCB/RBC transfusion, peripheral blood samples were collected, and the concentrations of 41 selected growth factors and their receptors were analyzed using a multiplex protein array. UCB transfusions were found to be both feasible and tolerable. Intraventricular haemorrhage was diagnosed in two of five (40%) UCB recipients, but was found in thirteen of fifteen RBC recipients (86.7%). Twenty-two plasma proteins (e.g., insulin-like growth factors, stem cell factor, epidermal growth factors) were found with significantly different concentrations in UCB recipients compared to controls. Results demonstrate safety and feasibility of UCB transfusion in a small group of very premature neonates and should be interpreted as preliminary speculation. Transfusion of UCB could induce a specific humoral effects, and this could serve as an adjuvant modality for prevention of prematurity complications.

Expression of neurotrophins and their receptors in human CD34+ bone marrow cells.

Bone marrow (BM) CD34+ cells have the ability to secrete growth factors, cytokines, and chemotactic factors. We sought to better characterize this population and to investigate whether human BM CD34+ cells express neurotrophins (NTs) and their relevant receptors. We also compared their expression levels with BM nucleated cells (NCs). BM CD34+ cells were evaluated with respect to the expression levels of neurotrophins using qRT-PCR, immunofluorescent staining, and Western blotting. Next, the expression of specific (TrkA, TrkB, TrkC) and non-specific (p75NTR) neurotrophin receptors was detected by qRT-PCR and immunofluorescent staining in BM CD34+ cells. Using qRT- PCR, we show that even in the absence of inducing factors, CD34+ cells spontaneously express neurotrophins such as NGF, BDNF, NT-3, and NT-4. In addition, the NT expression levels in BM CD34+ cells are considerably higher than in NCs. Furthermore, we confirmed intracellular NT expression in BM CD34+ cells at the protein level using immunofluorescent staining and Western blotting. Using qRT-PCR, we found that immunomagnetically separated BM CD34+ cells spontaneously express high-affinity neurotrophin receptors (TrkA, TrkB, and TrkC) and the low-affinity receptor p75NTR at higher levels than NCs. Immunomagnetic CD34+ cell separation enables for the rapid and gentle sorting of stem/progenitor cells (SPCs) to prepare specific cell types for use in research and clinical applications. Our study suggests that BM CD34+ cells have the potential to support trophic factors for neural tissue and could contribute towards the protection and regeneration of neural cells.

The influence of the tumor necrosis factor-alpa-308G>A polymorphism on the efficacy of immunosuppressive therapy in patients after kidney transplantation.

Cytokines play an important role in the immune response. The calcineurin inhibitors (cyclosporine CsA, tacrolimus TAC) widely used after renal transplantation to prevent allograft rejection are immunosuppressive drugs suppressing the production of cytokines. These drugs are characterized by interindividual variability and require monitoring their blood concentrations to predict their optimal dosage. Therefore, the aim of the study was to determine the correlation between therapeutic effects of immunosuppressants and the tumor necrosis factor-α (TNF-α)-308G>A polymorphism in renal transplant patients. A total of 412 patients receiving TAC and CsA were included in the study. Genotype frequencies were determined using the real-time PCR method. Patients with the GG genotype received higher doses of TAC as compared to carriers of the GA genotype (5.24 mg versus 3.35 mg) and had lower mean drug concentration in blood (5.86 ng/ml versus 6.92 ng/ml). Similar results were also obtained for CsA (GG: 185.33 mg versus GA: 153.30 mg, P < 0.05). The comparison of the TNF-α-308G>A polymorphism with the biochemical parameters did not reveal a potential risk for transplant rejection. These results indicate that the TNF-α-308G>A polymorphism may influence the dosage of immunosuppressive drugs in patients after transplantation as far as individualization of drug therapy is concerned.

Methylene blue usage in horseshoe kidney graft separation: case report.

Definitive diagnostics and strict procedures during kidney donor qualification are required. Nowadays, precise and accurate imaging techniques are at hand for every diagnostician. However, many studies have described intraoperative occurrence of horseshoe kidney. Although the harvesting procedure in the case of horseshoe kidney is not technically difficult, graft separation for successful renal transplantation is a challenge. The complex anatomy of malformed organs causes issues during kidney separation. This procedure may lead to damage of the collecting urinary system as well as vascularization damage. Separate graft transplantation is probable when a thin isthmus in a horseshoe kidney is present. Otherwise, poor graft function may occur. We present a technique for horseshoe kidney separation with the use of methylene blue for vascularization determination. The above-mentioned procedure was performed with the methylene blue solution dose injected into a single renal graft artery. Even with the malformed organ's thick isthmus, the exact incision line was identified, exposing vascular perfusion asymmetry and allowing precise renal graft separation.

Non-assisted versus neuro-navigated and XperCT-guided external ventricular catheter placement: a comparative cadaver study.

BACKGROUND AND PURPOSE: Accurate placement of an external ventricular drain (EVD) for the treatment of hydrocephalus is of paramount importance for its functionality and in order to minimize morbidity and complications. The aim of this study was to compare two different drain insertion assistance tools with the traditional free-hand anatomical landmark method, and to measure efficacy, safety and precision. METHODS: Ten cadaver heads were prepared by opening large bone windows centered on Kocher's points on both sides. Nineteen physicians, divided in two groups (trainees and board certified neurosurgeons) performed EVD insertions. The target for the ventricular drain tip was the ipsilateral foramen of Monro. Each participant inserted the external ventricular catheter in three different ways: 1) free-hand by anatomical landmarks, 2) neuronavigation-assisted (NN), and 3) XperCT-guided (XCT). The number of ventricular hits and dangerous trajectories; time to proceed; radiation exposure of patients and physicians; distance of the catheter tip to target and size of deviations projected in the orthogonal plans were measured and compared. RESULTS: Insertion using XCT increased the probability of ventricular puncture from 69.2 to 90.2 % (p = 0.02). Non-assisted placements were significantly less precise (catheter tip to target distance 14.3 ± 7.4 mm versus 9.6 ± 7.2 mm, p = 0.0003). The insertion time to proceed increased from 3.04 ± 2.06 min. to 7.3 ± 3.6 min. (p < 0.001). The X-ray exposure for XCT was 32.23 mSv, but could be reduced to 13.9 mSv if patients were initially imaged in the hybrid-operating suite. No supplementary radiation exposure is needed for NN if patients are imaged according to a navigation protocol initially. CONCLUSION: This ex vivo study demonstrates a significantly improved accuracy and safety using either NN or XCT-assisted methods. Therefore, efforts should be undertaken to implement these new technologies into daily clinical practice. However, the accuracy versus urgency of an EVD placement has to be balanced, as the image-guided insertion technique will implicate a longer preparation time due to a specific image acquisition and trajectory planning.

Stent-assisted coiling of bifurcation aneurysms may improve endovascular treatment: a critical evaluation in an experimental model.

BACKGROUND AND PURPOSE: Endovascular treatment of wide-neck bifurcation aneurysms often results in incomplete occlusion or aneurysm recurrence. The goals of this study were to compare results of coil embolization with or without the assistance of self-expandable stents and to examine how stents may influence neointima formation. MATERIALS AND METHODS: Wide-neck bifurcation aneurysms were constructed in 24 animals and, after 4-6 weeks, were randomly allocated to 1 of 5 groups: 1) coil embolization using the assistance of 1 braided stent (n = 5); 2) coil embolization using the assistance of 2 braided stents in a Y configuration (n = 5); 3) coil embolization without stent assistance (n = 6); 4) Y-stenting alone (n = 4); and 5) untreated controls (n = 4). Angiographic results were compared at baseline and at 12 weeks, by using an ordinal scale. Neointima formation at the neck at 12 weeks was compared among groups by using a semiquantitative grading scale. Bench studies were performed to assess stent porosities. RESULTS: Initial angiographic results were improved with single stent-assisted coiling compared with simple coiling (P = .013). Angiographic results at 12 weeks were improved with any stent assistance (P = .014). Neointimal closure of the aneurysm neck was similar with or without stent assistance (P = .908), with neointima covering coil loops but rarely stent struts. Y-stent placement alone had no therapeutic effect. Bench studies showed that porosities can be decreased with stent compaction, but a relatively stable porous transition zone was a limiting factor. CONCLUSIONS: Stent-assisted coiling may improve results of embolization by allowing more complete initial coiling, but these high-porosity stents did not provide a scaffold for more complete neointimal closure of aneurysms.

Thrombosis heralding aneurysmal rupture: an exploration of potential mechanisms in a novel giant swine aneurysm model.

BACKGROUND AND PURPOSE: The relationship between aneurysm dimensions, flow, thrombosis, and rupture remains poorly understood. We attempted to clarify this relationship by exploring various swine aneurysm models. MATERIALS AND METHODS: Bilateral carotid aneurysms were constructed according to 3 protocols in 24 animals: small aneurysms with wide necks (group 1; n = 6 animals); small aneurysms with small necks (group 2; n = 4 animals), and giant aneurysms with large necks (group 3; n = 14 animals). Group 3 included 3 subgroups, related to testing the model in various experimental conditions: The neck was clipped in 3 animals; venous pouches lacked an endothelial lining in 4 animals; and 7 were control animals. Animals were followed until rupture, or for 1-4 weeks. Angiography was performed postoperatively and before euthanasia. We studied lesion pathology, paying attention to thrombosis, recanalization, wall composition, and perianeurysmal hemorrhage. RESULTS: Groups differed significantly in aneurysm dimensions and aspect ratio (P = .002). Ruptures occurred more frequently in animals with untreated giant aneurysms (7/7) than in animals with small wide-neck (0/6) or small-neck (2/4) aneurysms (P = .002). Ruptures occurred only in animals with thrombosed aneurysms. Lesions lacking an endothelial lining and 5 of 6 clipped venous pouches thrombosed but did not rupture. One giant lesion ruptured despite complete clipping. The wall was deficient in α-actin and was infiltrated with inflammatory cells and erythrocytes in all thrombosed cases, ruptured or not. Ruptures were associated with recanalizing channels in 9 of 10 cases. CONCLUSIONS: Thrombosis, inflammation, and recanalization may precipitate aneurysmal ruptures in a swine model.

Ruptured aneurysms and the International Subarachnoid Aneurysm Trial (ISAT): What is known and what remains to be questioned.

BACKGROUND AND PURPOSE: The International Subarachnoid Aneurysm Trial (ISAT) was a major study comparing clipping and coiling of ruptured intracranial aneurysms. The trial provided answers that were the subject of multiple letters and editorial comments. METHODS: We review the most common critiques that were published in major neurosurgical journals, trying to identify what aspects of ISAT could have been improved, and what questions remain to be studied. RESULTS: Frequent critiques include imprecise selection criteria, lack of requirement for the technical proficiency of surgical participants, lack of angiographic controls of surgically treated patients, and poorly chosen primary endpoints. Other issues that are often raised are the poor recruitment rate which endangered generalization of results, the excessive delays in performing clipping which led to rebleeding episodes, lack of blinding in the assessment of outcomes, and subjective questionnaires. Nonetheless, the design of the study as a pragmatic trial was appropriate, as was the choice of the primary endpoint. The overall trial results could not be verified for all subgroups of interest, and currently many patients who would not have been included in ISAT are treated by coiling, while other patients are treated by clipping despite ISAT results. Hence a new trial, complementary to the original ISAT, may now be indicated. CONCLUSION: ISAT was well-designed and conducted, but many questions remain. They should be addressed by a new trial.

Systematic reviews of the literature on clipping and coiling of unruptured intracranial aneurysms.

BACKGROUND AND PURPOSE: The best management of unruptured aneurysms remains controversial. Accurate estimates of treatment-related morbidity and efficacy are needed for clinical decision making. METHODS: We review recent systematic reviews, case series and population-based studies on clipping and coiling of unruptured aneurysms. A critical analysis of the quality of available studies and of the reliability of results is followed by reappraisal of the logic of clinical research on unruptured aneurysms. RESULTS: Unfavourable outcome, including death, up to 1 year after surgical clipping, was found in 692 of 9845 patients (REW average: 6.7%; (99%)CI: 4.9-9.0). Unfavourable outcome after coiling occurred in 189 of 5044 patients (REW average 4.8%, ((99%)CI: 3.9-6.0). Location and size of aneurysms were risk factors for clipping, while no risk factor reached statistical significance for coiling studies. The quality of reports was in general poor. Estimates from epidemiological studies showed higher morbidity rates than reviews of case series. Treatment efficacy could not be assessed. All studies are attempts to provide answers to questions that were never properly raised. CONCLUSION: Results of reviews and observational studies should serve as hypotheses for clinical trials.

How to choose clipping versus coiling in treating intracranial aneurysms.

BACKGROUND: After the decision is made to treat an intracranial aneurysm, clinicians must choose between two competing treatment options; open surgery or endovascular therapy. The rationale underlying the choice of treatment modality is usually unclear, as there is little good quality evidence available. METHODS: We discuss the patient and aneurysm-related factors cited in the neurovascular literature that are considered to influence aneurysm treatment choices. RESULTS: The relevance and direction of influence of rupture status, age, type of presentation, and general medical condition, as well as aneurysm size, location, morphology, and multiplicity are discussed. The validity of these factors in influencing treatment decisions remains unclear, with frequently opposing views on the same factor by clinicians practicing opposing techniques. Perceived differences in efficacy and safety of the two different treatment approaches are commonly used in an attempt to justify treatment choices. Difficulties with treatment selection and case-by-case reasoning are reviewed. CONCLUSION: Properly designed and conducted randomized trials are necessary in order to settle the controversy and to determine the optimal treatment modality for intracranial aneurysms. In the absence of reliable knowledge on which to base treatment decisions, the ethically appropriate choice for any clinician, from surgical or endovascular backgrounds, is to participate in randomized trials.