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Pilot clinical trials have shown the safety of intra-arterial bone marrow mononuclear cells (BMMNCs) in stroke. However, the efficacy of different doses of intra-arterial BMMNCs in patients with acute stroke has not been tested in a randomised clinical trial. We aimed to show safety and efficacy of two different doses of autologous intra-arterial BMMNC transplantation in patients with acute stroke. The IBIS trial was a multicentre phase 2, randomised, controlled, investigator-initiated, assessor-blinded, clinical trial, in four stroke centres in Spain. We included patients (aged 18–80 years) with a non-lacunar, middle cerebral artery ischaemic stroke within 1–7 days from stroke onset and with a National Institutes of Health Stroke Scale score of 6–20. We randomly assigned patients (2:1:1) with a computer-generated randomisation sequence to standard of care (control group) or intra-arterial injection of autologous BMMNCs at one of two different doses (2 × 106 BMMNCs/kg or 5 × 106 BMMNCs/kg). The primary efficacy outcome was the proportion of patients with modified Rankin Scale scores of 0–2 at 180 days in the intention-to-treat population, comparing each BMMNC dose group and the pooled BMMNC group versus the control group. The primary safety endpoint was the proportion of serious adverse events. This trial was registered at ClinicalTrials.gov, NCT02178657 and is completed. Between April 1, 2015, and May 20, 2021, we assessed 114 patients for eligibility. We randomly assigned 77 (68%) patients: 38 (49%) to the control group, 20 (26%) to the low-dose BMMNC group, and 19 (25%) the high-dose BMMNC group. The mean age of participants was 62·4 years (SD 12·7), 46 (60%) were men, 31 (40%) were women, all were White, and 63 (82%) received thrombectomy. The median NIHSS score before randomisation was 12 (IQR 9–15), with intra-arterial BMMNC injection done a median of 6 days (4–7) after stroke onset. The primary efficacy outcome occurred in 14 (39%) patients in the control group versus ten (50%) in the low-dose group (adjusted odds ratio 2·08 [95% CI 0·55–7·85]; p=0·28), eight (44%) in the high-dose group (1·89 [0·52–6·96]; p=0·33), and 18 (47%) in the pooled BMMNC group (2·22 [0·72–6·85]; p=0·16). We found no differences in the proportion of patients who had adverse events or dose-related events, but two patients had a groin haematoma after cell injection in the low-dose BMMNC group. Intra-arterial BMMNCs were safe in patients with acute ischaemic stroke, but we found no significant improvement at 180 days on the mRS. Further clinical trials are warranted to investigate whether improvements might be possible at different timepoints. Instituto de Salud Carlos III co-funded by the European Regional Development Fund/European Social Fund, Mutua Madrileña, and the Regional Ministry of Health of Andalusia.

BackgroundSeveral antithrombotic treatments during emergent carotid artery stenting (eCAS) have been proposed, but an appropriate protocol to balance risk–benefit is not well known.ObjectiveTo investigate the efficacy and safety of tirofiban compared with aspirin in patients with acute ischemic stroke undergoing eCAS.MethodsWe conducted a retrospective single-center study of the prospective ARTISTA Registry, including patients with atherosclerotic internal carotid artery occlusion treated with eCAS. Two groups, according to antiplatelet drug, were studied: aspirin (250–500 mg single-dose) versus tirofiban (500 μg bolus+200 μg/h). Primary outcomes were the rate of in-stent thrombosis and symptomatic intracranial hemorrhage (sICH) within the first 24 hours.ResultsDuring the period 2019–2023, 181 patients were included, 103 received aspirin, 78 tirofiban; 149 (82.3%) had tandem lesions. The primary efficacy outcome occurred in 9 (9.4%) in the aspirin group, as compared with 1 (1.3%) in the tirofiban group (adjusted odds ratio (aOR)=0.11, 95% CI 0.01 to 0.98; P=0.048). The primary safety outcome was detected in 12 (11.7%) in the aspirin group, as compared with 2 (2.6%) in the tirofiban group (aOR=0.16, 95% CI 0.03 to 0.87; P=0.034). The tirofiban group presented a lower risk of parenchymal hemorrhage (18 (17.4%) vs 4 (5.2%), aOR=0.27, 95% CI 0.09 to 0.88; P=0.029) and an increased rate of excellent recanalization (expanded Treatment in Cerebral Infarction (eTICI) 2c–3) (50 (48.5%) vs 54 (69.2%); aOR=2.15, 95% CI 1.12 to 4.13; P=0.02). There were no differences in functional outcomes or mortality at 3 months.ConclusionsPeriprocedural antithrombotic therapy with tirofiban was associated with a lower risk of in-stent thrombosis and sICH at 24 hours from eCAS compared with aspirin. Prospective randomized clinical trials are needed to confirm our results.

•The stiff person syndrome (SPS) is difficult to diagnose and to treat.•Paraneoplastic SPS with anti-Ri antibodies is less known.•Early antitumoral therapy should be the first step in these cases.•SPS has not been described in bladder cancer to date.•This case report expands the spectrum of paraneoplastic SPS. The stiff person syndrome is a rare neurological disorder, difficult to diagnose and to treat. Paraneoplastic patients usually present amphiphysin antibodies but the association with anti-Ri antibodies is less known. We present a case report of paraneoplastic SPS, small cell carcinoma of the bladder and anti-Ri antibodies.

BackgroundThe management of clopidogrel in hyper-responders has not been well described. We report the treatment and dose adjustment individualization with clopidogrel oral solution (COS) in hyper-responder patients with an unruptured intracranial aneurysm treated with a stent.MethodsA prospective study (2015–2018) in patients receiving clopidogrel prior to endovascular treatment was performed. Platelet reactivity after clopidogrel therapy was evaluated with the VerifyNow PRU test. Initial values ≤80 PRU (P2Y12 reactivity units) were classified as a hyper-response according to prior evidence. Patients were treated with clopidogrel for 7–10 days before stent treatment. Seven days post-procedure the dose of COS was gradually reduced (30 mg–20 mg–10 mg–5 mg) every 5 days to 5 mg (1 mL)/day.ResultsTwenty patients with 24 aneurysms were classified as having a hyper-response to clopidogrel. Mean age was 55.2 years (range 42–64) and 80% were women. Mean baseline PRU value and the percentage of platelet inhibition were 16.4±11.5 PRU and 92.05±7.5%, respectively. The mean time used to decrease the dose of clopidogrel to 5 mg/day was 27±4.3 days. Modified dosing strategies were shown to increase the final PRU values and to decrease the percentage of platelet inhibition (137.42±27.4 and 41.5±14.8%, respectively). Two of the 20 patients with dose adjustment of oral solution of clopidogrel (5 mg/day) in our cohort exhibited a delayed conversion to hypo-response. No patients suffered thromboembolic events related to the dose adjustment of clopidogrel with 5 mg/day during the follow-up.ConclusionReduction of the daily maintenance dose of clopidogrel in hyper-responder patients could provide a similar antiplatelet effect to the standard dose of clopidogrel, allowing a PRU value in the optimal range.

Rationale In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. Aims To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Sample size estimates Two hundred forty patients will be enrolled, 120 in every treatment arm. Methods and design A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. Study outcomes Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. Discussion This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. Trial registration The trial is registered as NCT05225961. February, 7th, 2022.