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The linear μ-carbido complex [Rh2(μ-C)Cl2(dppm)2] (dppm = bis(diphenylphosphino)methane) reacts with a benzyne equivalent (Me3SiC6H4OTf-2/F-) to afford [Rh2(μ-CC6H4)(μ-Cl)(C6H5)Cl2(μ-dppm)2], in which the benzyne moiety adds across one of the two metal-carbon double bonds.

The μ-carbido complexes [Rh 2 (μ-C)Cl 2 (PPh 3 ) 4 ] and [Rh 2 (μ-C)Cl 2 (dppm) 2 ] cleave CS 2 to afford the monothiocarbonyl complexes [RhCl(CS)(PPh 3 ) 2 ] and [Rh 2 (μ-CS)Cl 2 (dppm) 2 ]. The latter reacts with dimethyl acetylenedicarboxylate (DMAD) to afford [Rh(μ-CS)(μ-DMAD)Cl 2 (dppm) 2 ]. This complex is also formed from [Rh(μ-C)(μ-DMAD)Cl 2 (dppm) 2 ] and sulfur. These strategies also afford the first rhodium selenocarbonyl complexes [Rh(μ-CSe)Cl 2 (dppm) 2 ] and [Rh(μ-CSe)(μ-DMAD)Cl 2 (dppm) 2 ].

The reaction of [Rh2(μ-C)Cl2(PPh3)4] with 1,1'-bis(diphenylphosphino)ferrocene (dppf) affords the μ-carbido complex [Rh2(μ-C)Cl2(μ-dppf)2] which reacts with PhICl2 to provide a diamagnetic dirhodium(ii) carbido complex [Rh2(μ-C)Cl4(μ-dppf)2].

The linear μ-carbido complex [Rh 2 (μ-C)Cl 2 (dppm) 2 ] (dppm=bis(diphenylphosphino)methane) reacts with dimethylacetylene dicarboxylate (DMAD) to afford [Rh 2 (μ-C)(μ-DMAD)Cl 2 (dppm) 2 ], which features a bent RhCRh linkage (124.7°) that might be described as a dirhoda-heterocyclic carbene, as demonstrated by coordination to further metal centers., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The reaction of [Rh2(μ-C)Cl2(PPh3)4] with bis(diphenylphosphino)methane (dppm) affords the A-frame μ-carbido complex [Rh2(μ-C)Cl2(μ-dppm)2], halide metathesis of which provides [Rh2(μ-C)Br2(μ-dppm)2]. The reactions of the former with PhICl2 or the latter with [pyH][Br3] provide rare examples of μ2-halocarbyne ligands in the complexes [Rh2(μ-CX)(μ-X)X4(μ-dppm)2] (X = Cl, Br).

The reaction of [RhCl(CS)(PPh3)2] with excess catecholborane affords the cumulenic carbido complex [Rh2(μ-C)Cl2(PPh3)4] which undergoes phosphine and halide substitution to afford a range of complexes in which the Rh[double bond, length as m-dash]C[double bond, length as m-dash]Rh spine remains intact. Amongst these, the reactions with K[L] (L = H2B(pz)2, H2B(pzMe2)2, HB(pz)3; pz = pyrazol-1-yl) afford [Rh2(μ-C)(PPh3)2(L)2] whilst with K[HB(pzMe2)3] the unsymmetrical complex [Rh2H(μ-C)(μ-C6H4PPh2-2){HB(pzMe2)3}2] is obtained in which the carbido ligand spans d6-Rh(iii) and d8-Rh(i) centres.

Supported by the Canadian Medical Research Council we performed a randomized trial extending from Newfoundland to British Columbia. With others a number of observations showed that aspirin will reduce stroke. With National Institute of Neurological Disorders and Stroke support we learned who would benefit and not from surgery in these stroke threatened carotid diseased patients. We evaluated the upper limits of acceptability of complications beyond which harm was done. Amassing this large data base of approximately 5000 individuals, followed for five years, previously unknown carotid phenomena were observed: 1. Ischemic stroke occurs in patients with prolapsing mitral valves; 2. There is risk of stroke in patients with residual thrombi in the occluded stump of the carotid artery; 3. We detected a lower risk than expected in patients with nearly occluded carotid arteries. We support the contention of Yusuf and Cairns' that Canada needs to give more financial support to purely clinical research. It pays off !

Large scale, international clinical trials are formidable challenges, but they are the most effective means of answering important clinical questions in a definitive, generalizable manner. They require adequate funding and must be rigorously conducted. Much can be gleaned from such studies, which address the important research questions and provide answers to related questions. Such trials are enormously rewarding and are worth the expense and effort.

Francesco I de' Medici (1541-1587), the second Grand Duke of Tuscany, was one of the members of the Medici family who ruled Florence during the centuries of the Renaissance. When, in 1857, all members of the Medici family were exhumed and definitively buried in the place where they still lie buried today, a painter, Giuseppe Moricci (Florence 1806-1879), who attended the ceremony, depicted the corpse of Francesco I in a perfect state of preservation. The painting shows a right spastic hemiparesis with a facial droop, a claw-hand appearance, the right shoulder internally rotated, the calf muscle wasted and the clubfoot confirmed by an orthopedic footwear in the coffin. The hemiparesis and consequent disability were likely concealed when Francesco I was alive, since in official portraits the Grand Duke appeared in perfect physical condition. However, chronicles reported that he had suffered from malaria and syphilis. Later in his life, temper and behavioral changes as well as emotional instability were documented, together with handwriting deterioration and seizures. We postulate that Francesco I had suffered from a stroke consequent to syphilis, a new aggressive and rapidly spreading infectious disease at that time in Italy. Francesco's governmental skills were presumably altered due to these diseases. Disability consequent to stroke was likely concealed by official portrayers and biographers of Francesco I during his life, consistent with the King's two bodies theory common since the Middle Ages: while the King's physical body is destined to die, the political one is everlasting. Infectious diseases have remained a leading cause of stroke in underdeveloped countries until recently, but noncommunicable causes are now prevailing worldwide., (Copyright © 2012 S. Karger AG, Basel.)

Carotid angioplasty and stenting has become a popular alternative to carotid endarterectomy for the treatment of carotid stenosis in stroke. Evidence from early randomized controlled trials comparing these interventions revealed mixed results. The largest such trial, the Carotid Revascularization Endarterectomy vs. Stenting Trial recently showed equivalence of the procedures in a mixed cohort of both symptomatic and asymptomatic patients. These results have been heralded in North America as definitively demonstrating the safety and efficacy of carotid angioplasty and stenting, making it an attractive alternative to carotid endarterectomy. It is therefore probable that many more asymptomatic patients will be subjected to Carotid angioplasty and stenting, perceived by many to be less invasive than carotid endarterectomy. The authors argue that the design of Carotid Revascularization Endarterectomy vs. Stenting Trial was flawed by the mixture of two dissimilar patient groups, thus violating the principle of ceteris paribus, essential for the validity of a randomized controlled trials. The evidence for any invasive treatment of asymptomatic carotid disease is weak, with recent data favouring purely medical management. The authors believe that carotid angioplasty and stenting in asymptomatic patients should cease until better evidence is available., (© 2010 The Authors. International Journal of Stroke © 2010 World Stroke Organization.)

Endarterectomy is generally recommended for symptomatic high-grade (70 to 99%) stenosis of the internal carotid artery, but whether this procedure is beneficial among patients with chronic kidney disease (CKD) is unknown. In this re-analysis of data from the North American Symptomatic Carotid Endarterectomy Trial, we included patients with symptomatic stenosis and either stage 3 CKD (n = 524) or preserved kidney function (n = 966; estimated GFR > or = 60). For medically treated patients with high-grade stenosis, risk for ipsilateral stroke at 2 yr was significantly higher in patients with CKD than in those with preserved renal function (31.6 versus 19.3%; P = 0.042); carotid endarterectomy significantly reduced this risk by 82 and 51%, respectively. To prevent one ipsilateral stroke, the number needed to treat by endarterectomy was four for patients with CKD and 10 for patients with preserved renal function. Compared with patients with preserved renal function, those with CKD had similar rates of perioperative stroke and death but higher rates of cardiac events. In conclusion, patients with stage 3 CKD and symptomatic high-grade carotid stenosis gain a large benefit in stroke risk reduction after endarterectomy.

Background: Studies suggest that the side of carotid endarterectomy (CE) may influence the rate of postoperative complications. We sought to clarify this by (1) analysis of individual-level data from 3 large studies and (2) systematic review and meta-analysis of additional published descriptions of outcomes by side., Methods and Results: The Western Canada Carotid Endarterectomy (WCCE) study (n=3164) was analyzed for outcomes by side along with data from the North American Symptomatic Carotid Endarterectomy Trial (NASCET; n=1415), and the ASA [Acetylsalicylic Acid] in Carotid Endarterectomy Trial (ACE; n=2469). Pooled analysis of individual-level data from these three studies allowed calculation of rate ratios for stroke or death by side. Medline and EMBASE were searched to identify additional studies reporting CE outcomes by side, and an overall risk ratio for outcomes by side was determined with fixed-effects meta-analysis. The WCCE in-hospital stroke or death rates for left and right-sided CE were 3.72% and 3.07%, respectively (P=0.27). A pooled analysis of the NASCET and ACE trials also revealed higher stroke or death rates for left-sided CE (5.39% versus 2.96%; P<0.001). The corresponding risk-adjusted rate ratios for stroke or death for left- versus right-sided surgery were 1.22 (95% CI, 0.83 to 1.77) for WCCE and 1.82 (1.32 to 2.50) for the pooled NASCET and ACE trials. Systematic review of the literature identified 2 additional studies. Meta-analysis of all 5 available studies yielded a corresponding pooled rate ratio for stroke or death of 1.36 (1.18 to 1.56)., Conclusions: Left-sided CE is consistently associated with higher postoperative adverse event rates. Research into potential mechanisms is required to explain and address this finding.

Background and Purpose: Two large trials indicated that endarterectomy was less beneficial for symptomatic patients with internal carotid artery (ICA) near occlusion than for patients who had severe stenosis without near occlusion. Near occlusions complicate ratio calculations of ICA stenosis and require attention to detail for identification. The goal is to provide diagnostic criteria, illustrate identifying features, estimate accuracy of identification, and assess prognosis for patients with near occlusion., Methods: We re-reviewed 1216 patients with severe (> or =70%) stenosis on angiography in the North American Symptomatic Carotid Endarterectomy Trial and European Carotid Surgery Trial. One of 5 (n = 262) had 2 or more criteria for near occlusion: (1) delayed cranial arrival of ICA contrast compared with external carotid artery (ECA); (2) intracranial collaterals seen as cross-filling of contralateral vessels or ipsilateral contrast dilution; (3) obvious diameter reduction of ICA compared with opposite ICA; or (4) ICA diameter reduction compared with ipsilateral ECA., Results: Interrater agreement, sensitivity, and specificity were excellent (0.88, 90.6%, and 93.8%, respectively). By intention to treat, 3-year risks of ipsilateral stroke for medically treated patients with near occlusion was 15.1% versus 10.9% for surgically treated (absolute risk reduction [ARR] = 4.2%; P value = .33). Patients who continued to receive treatment in the medical arm for the trial's duration had a 3-year risk of 18.3% (ARR = 7.4%; P value = .13). Medically treated patients with severe stenosis but without near occlusion had a 3-year risk of 26.0% versus surgically treated of 8.2% (ARR = 17.8%; P value < .001)., Conclusion: It is crucial to identify near occlusions on vascular imaging. Although it still is reasonable to consider endarterectomy for these patients, the benefit is muted.

Background and Purpose: To determine the relationship between ulceration, thrombus, and calcification of carotid artery atherosclerotic plaques and symptoms of ipsilateral or contralateral stroke., Methods: We compared microscopic plaque morphology from patients with and without stroke symptoms ipsilateral or contralateral to the plaque. Plaques were characterized for ulceration, thrombus, and calcification. We analyzed plaques from 241 subjects: 170 patients enrolled in the Asymptomatic Carotid Atherosclerosis Study (ACAS) and 71 patients enrolled in the North American Symptomatic Carotid Endarterectomy Trial (NASCET); 128 subjects had no history of stroke symptoms, 80 subjects had ipsilateral symptoms, and 33 had contralateral symptoms., Results: Plaque ulceration was more common in plaques taken from symptomatic patients than those without symptoms (36% versus 14%; P<0.001); frequency of ulceration was similar for plaques associated with ipsilateral (34%) and contralateral (42%) symptoms. Thrombus was most common in plaques taken from patients with both ipsilateral symptoms and ulceration. The extent of calcification was unassociated with stroke symptoms., Conclusions: Carotid plaque ulceration and thrombosis are more prevalent in symptomatic patients. Ulceration is more common in symptomatic patients regardless of side of carotid symptoms, whereas thrombus is associated with ipsilateral symptoms and plaque ulceration. Preoperative identification of carotid ulceration and thrombus should lead to greater efficacy of stroke prevention by carotid endarterectomy.

Background and Purpose: Perioperative risk and long-term benefit of carotid endarterectomy (CE) are not detailed in women with symptomatic internal carotid artery (ICA) stenosis. Our aim was to compare the efficacy of CE versus medical therapy in women and men with symptomatic ICA stenosis., Methods: Data were taken from the North American Symptomatic Carotid Endarterectomy Trial (873 women, 2012 men) and the ASA and Carotid Endarterectomy trial (335 women, 813 men)., Results: The 30-day perioperative risk of death was higher in women than in men (2.3% versus 0.8%, P=0.002). Higher perioperative risk of stroke and death was also observed (7.6% versus 5.9%) but not statistically significant. With > or =70% stenosis, the 5-year absolute risk reduction (ARR) in stroke from CE was similar between women (15.1%) and men (17.3%). With 50% to 69% stenosis, CE was not beneficial in women (ARR=3.0%, P=0.94), contrary to men (ARR=10.0%, P=0.02). Medically treated women had low risk for stroke. A stroke prognosis instrument (SPI-II) assigned points to 7 factors that identified higher risk for medically treated women: 3 points for hemispheric (not retinal) event, history of diabetes, previous stroke; 2 for age older than 70 years, stroke (not transient ischemic attack); 1 for severe hypertension, history of myocardial infarction. CE was beneficial only for 29.0% of women with 50% to 69% stenosis who had the highest total score of 8 to 15 (ARR=8.9%)., Conclusions: Women and men with > or =70% symptomatic stenosis had similar long-term benefit from CE, although the perioperative risks were higher for women. CE was not beneficial for women with 50% to 69% stenosis without other risk factors for stroke.

Background and Purpose: Early studies showed that carotid endarterectomy (CEA) carried a high risk if performed within days after a large ischemic stroke. Therefore, many surgeons delay CEA for 4 to 6 weeks after any stroke. To determine the effect of delay to CEA on operative risk and benefit, we pooled data from the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial., Methods: Risk of ipsilateral ischemic stroke in the medical group, operative risk of stroke and death, and overall benefit from surgery were determined in relation to the time from the last symptomatic event to randomization. Operative risk of stroke and death was also determined in relation to the time to surgery. Analyses were stratified by sex and type of presenting event., Results: The 30-day perioperative risk of stroke and death was unrelated to the time since the last symptomatic event and was not increased in patients operated <2 weeks after nondisabling stroke. In contrast, the risk of ipsilateral ischemic stroke in the medical group fell rapidly with time since event (P<0.001), as did the absolute benefit from surgery (P=0.001). This decline in benefit with time was unrelated to the type of presenting event but was more pronounced in women than men (difference P<0.001). Benefit in women was confined to those randomized <2 weeks after their last event, irrespective of severity of stenosis., Conclusions: CEA can be performed safely within 2 weeks of nondisabling ischemic stroke. Benefit from endarterectomy declines rapidly with increasing delay, particularly in women.

Background: Transient ischemic attacks (TIAs) often herald a stroke, but little is known about the acute natural history of TIAs. Our objective was to quantify the early risk of stroke after a TIA in patients with internal carotid artery disease., Methods: Using patient data from the medical arm of the North American Symptomatic Carotid Endarterectomy Trial, we calculated the risk of ipsilateral stroke in the territory of the symptomatic internal carotid artery within 2 and 90 days after a first-recorded hemispheric TIA. We also studied similar outcomes among patients in the trial who had a first-recorded completed hemispheric stroke., Results: For patients with a first-recorded hemispheric TIA (n = 603), the 90-day risk of ipsilateral stroke was 20.1% (95% confidence interval [CI] 17.0%-23.2%), higher than the 2.3% risk (95% CI 1.0%-3.6%) for patients with a hemispheric stroke (n = 526). The 2-day risks were 5.5% and 0.0%, respectively. Patients with more severe stenosis of the internal carotid artery (> 70%) appeared to be at no greater risk of stroke than patients with lesser degrees of stenosis (adjusted hazard ratio 1.1, 95% CI 0.7-1.7). Infarct on brain imaging (adjusted hazard ratio 2.1, 95% CI 1.5-3.0) and the presence of intracranial major-artery disease (adjusted hazard ratio 1.9, 95% CI 1.3-2.7) doubled the early risk of stroke in patients with a hemispheric TIA., Interpretation: Patients who had a hemispheric TIA related to internal carotid artery disease had a high risk of stroke in the first few days after the TIA. Early risk of stroke was not affected by the degree of internal carotid artery stenosis.

Background: Carotid endarterectomy reduces the risk of stroke in patients with recently symptomatic stenosis. Benefit depends on the degree of stenosis, and we aimed to see whether it might also depend on other clinical and angiographic characteristics, and on the timing of surgery., Methods: We analysed pooled data from the European Carotid Surgery Trial and North American Symptomatic Carotid Endarterectomy Trial. The risk of ipsilateral ischaemic stroke for patients on medical treatment, the perioperative risk of stroke and death, and the overall benefit from surgery were determined in relation to seven predefined and seven post hoc subgroups., Results: 5893 patients with 33000 patient-years of follow-up were analysed. Sex (p=0.003), age (p=0.03), and time from the last symptomatic event to randomisation (p=0.009) modified the effectiveness of surgery. Benefit from surgery was greatest in men, patients aged 75 years or older, and those randomised within 2 weeks after their last ischaemic event, and fell rapidly with increasing delay. For patients with 50% or higher stenosis, the number of patients needed to undergo surgery (ie, number needed to treat) to prevent one ipsilateral stroke in 5 years was nine for men versus 36 for women, five for age 75 years or older versus 18 for younger than 65 years, and five for those randomised within 2 weeks after their last ischaemic event, versus 125 for patients randomised after more than 12 weeks. These results were consistent across the individual trials., Interpretation: Benefit from endarterectomy depends not only on the degree of carotid stenosis, but also on several other clinical characteristics such as delay to surgery after the presenting event. Ideally, the procedure should be done within 2 weeks of the patient's last symptoms.

Background and Purpose: Current publications suggest increased risk of sudden death in experimental animals with acute right insular lesions and in patients with recent right-sided brain infarction, particularly if the insula is involved., Methods: Using 3 different time definitions, we related long-term risk of sudden death to presence and side of brain infarction on the baseline brain scan and handedness in 2885 patients with symptomatic carotid disease., Results: In 1295 patients without brain infarction, 5-year risk of sudden death was 5.3% (24-hour definition); in those with left-sided infarction (n=471), 8.8%; in those with right-sided infarction (n=477), 6.0%; and in those with bilateral infarction (n=535), 9.7%. After accounting for differences of other risk factors (eg, previous myocardial infarction) in Cox regression, adjusted hazard ratios (HRs) compared with no infarction were as follows: left-sided HR, 1.45 (95% confidence interval [CI], 1.00 to 2.10); right-sided HR, 0.96 (95% CI, 0.62 to 1.47); and bilateral HR, 1.40 (95% CI, 0.98 to 2.00). Insular infarction occurred in 41 patients; none died suddenly. Left-handed or ambidextrous patients (n=183) had a lower risk of sudden death than right-handers; the adjusted HR for left-handed or ambidextrous patients was 0.24 (95% Cl, 0.07 to 0.70). These results were essentially the same for the 10- and 60-minute definitions of sudden death., Conclusions: In the long-term, left-sided, not right-sided, brain infarction is associated with increased risk of sudden death. Left-handed or ambidextrous patients have a lower risk of sudden death than right-handed patients, suggesting a role for the brain.