Predictors of futile recanalization in nonagenarians treated with mechanical thrombectomy: a multi-center observational study.

BACKGROUND: There is a lack of data regarding patients aged 90 years or older undergoing mechanical thrombectomy and their predictors of futile recanalization. AIMS: We sought to evaluate the predictors of futile recanalization in patients ≥ 90 years with large vessel occlusion undergoing mechanical thrombectomy. METHODS: This multi-center observational retrospective study included patients ≥ 90 years consecutively treated with mechanical thrombectomy in four thrombectomy capable centers between January 1st, 2016 and 30th March 2023. Futile recanalization was defined as large vessel occlusion patients experiencing a 90-day poor outcome (mRS 3-6) despite successful recanalization (mTICI ≥ 2b) after mechanical thrombectomy. RESULTS: Our cohort included 139 patients ≥ 90 years with acute ischemic stroke due to anterior circulation large vessel occlusion treated with mechanical thrombectomy. One hundred seventeen of one hundred thirty-nine patients ≥ 90 years who achieved successful recanalization were included in the analysis (seventy-six female (64.9%)), of whom thirty-one (26.49%) experienced effective recanalization and eighty-six (73.51%) experienced futile recanalization. Patients with futile recanalization had higher NIHSS on admission (p < 0.001); they were less frequently treated with intravenous thrombolysis (p = 0.048), had more often general anesthesia (p = 0.011), and longer door to groin puncture delay (p = 0.002). Univariable regression analysis showed that use of intravenous thrombolysis (0.29, 95% CI 0.02-0.79, p = 0.034) and site of occlusion distal vs proximal (0.34, 95% CI 0.11-0.97, p = 0.044) were associated with reduced probability of futile recanalization while NIHSS on admission (1.29, 95% CI 1.16-1.45, p < 0.001), NIHSS at 24 h (1.15, 95% CI 1.07-1.25, p = 0.002), type of anesthesia used (4.18, 95% CI 1.57-11.08, p = 0.004), and door to groin puncture time (1.02, 95% CI 1.00-1.05, p = 0.005) were associated with increased probability of futile recanalization. Multivariable regression analysis showed that use of intravenous thrombolysis (0.44, 95% CI 0.09-0.88, p = 0.039) was associated with reduced probability of futile recanalization. CONCLUSION: Our study seems to suggest that mechanical thrombectomy with intravenous thrombolysis is associated with reduced probability of futile recanalization in a multi-center cohort of patients aged 90 years or older.

Preoperative elastoplasty of aggressive vertebral hemangiomas in elderly patients: a new strategy for reducing intraoperative bleeding and complications.

PURPOSE: Preoperative elastoplasty could be an alternative strategy for treating aggressive vertebral hemangiomas (VHs) in frail patients needing for spinal cord decompression, combining the advantages of embolization and vertebroplasty. METHODS: Three elderly patients with spinal cord compression from thoracic aggressive VHs underwent XperCT-guided percutaneous injection of silicone (VK100), filling the whole affected vertebra, followed by a decompressive laminectomy. At 12-months follow-up no recurrences, vertebral collapse or segmental kyphosis were noted at the CT scans, with patients reporting an improvement of preoperative neurological deficits, VAS and Smiley-Webster pain scale (SWPS) parameters. RESULTS: With its elastic modulus, non-exothermic hardening, and lower viscosity than PMMA, VK100 allowed a preoperative augmentation of the affected vertebral body, pedicles, and laminae without complications, with a controlled silicone delivery even in part of VH's epidural components thanks to XperCT-guidance. CONCLUSION: When facing highly bony erosive VH encroaching the spinal canal, VK100 combines the advantages of embolization and vertebroplasty especially in elderly patients, permeating the whole VH's angioarchitecture, significantly reducing tumor.

Multiannual patterns of genetic structure and mating type ratios highlight the complex bloom dynamics of a marine planktonic diatom.

Understanding the genetic structure of populations and the processes responsible for its spatial and temporal dynamics is vital for assessing species' adaptability and survival in changing environments. We investigate the genetic fingerprinting of blooming populations of the marine diatom Pseudo-nitzschia multistriata in the Gulf of Naples (Mediterranean Sea) from 2008 to 2020. Strains were genotyped using microsatellite fingerprinting and natural samples were also analysed with Microsatellite Pool-seq Barcoding based on Illumina sequencing of microsatellite loci. Both approaches revealed a clonal expansion event in 2013 and a more stable genetic structure during 2017-2020 compared to previous years. The identification of a mating type (MT) determination gene allowed to assign MT to strains isolated over the years. MTs were generally at equilibrium with two notable exceptions, including the clonal bloom of 2013. The populations exhibited linkage equilibrium in most blooms, indicating that sexual reproduction leads to genetic homogenization. Our findings show that P. multistriata blooms exhibit a dynamic genetic and demographic composition over time, most probably determined by deeper-layer cell inocula. Occasional clonal expansions and MT imbalances can potentially affect the persistence and ecological success of planktonic diatoms.

Baseline clinical and neuroradiological predictors of outcome in patients with large ischemic core undergoing mechanical thrombectomy: A retrospective multicenter study.

BACKGROUND: Recent randomized trials have shown the benefit of mechanical thrombectomy (MT) also in patients with an established large ischemic core. AIMS: The purpose of this study was to define baseline predictors of clinical outcome in patients with large vessel occlusion (LVO) in the anterior circulation and an Alberta Stroke Program Early CT score (ASPECTS) ⩽ 5, undergoing MT. MATERIAL AND METHODS: The databases of 16 comprehensive stroke centers were retrospectively screened for patients with LVO and ASPECTS ⩽5 that received MT. Baseline clinical and neuroradiological features, including the differential contribution of all ASPECTS regions to the composite score, were collected. Primary clinical outcome measure was a 90-day modified Rankin Scale (mRS) score of 0-2. Statistical analysis used a logistic regression model and random forest algorithm. RESULTS: A total of 408 patients were available for analysis. In multivariate model, among baseline features, lower age (odd ratio (OR) = 0.962, 95% confidence interval (CI) = 0.943-0.982) and lower National Institute of Health Stroke Scale (NIHSS) score (OR = 0.911, 95% CI = 0.862-0.963) were associated with the mRS score 0-2. Involvement of the M2 (OR = 0.398, 95% CI = 0.206-0.770) or M4 (OR = 0.496, 95% CI = 0.260-0.945) ASPECTS regions was associated with an unfavorable outcome. Random forest analysis confirmed that age and baseline NIHSS score are the most important variables influencing clinical outcome, whereas involvement of cortical regions M5, M4, M2, and M1 can have a negative impact. CONCLUSION: Our retrospective analysis shows that, along with age and baseline clinical impairment, presence of early ischemic changes involving cortical areas has a role in clinical outcome in patients with large ischemic core undergoing MT. DATA ACCESS STATEMENT: The data that support the findings of this study are available upon reasonable request.

The severity of early fluid overload assessed by bioelectrical vector impedance as an independent risk factor for longer patient care after cardiac surgery.

BACKGROUND AND AIMS: Fluid overload is a common postoperative complication in patients undergoing cardiac surgery. Although this condition is notably associated with relevant adverse outcomes, assessment of hydration status in clinical practice is challenging. Bioelectrical impedance vector analysis (BIVA) has emerged as a potentially effective method to monitor hydration changes, but the available evidence in critically ill patients undergoing cardiac surgery is limited and sometimes conflicting. The aim of this study was to explore by mean of BIVA the evolution over time of hydration status and its impact on relevant outcomes. METHODS: Prospective observational study enrolling 130 patients undergoing cardiac surgery. Height normalized impedance was calculated both before surgery (baseline) and in the first five postoperative days. Relevant clinical and laboratory data were collected daily close to BIVA measurements. Length of mechanical ventilation (MV), intensive care unit (ICU) and hospital stay exceeding the 75th percentile of the study population were considered as study endpoints. RESULTS: Compared to baseline, a significant reduction in impedance was found at first postoperative day, demonstrating a relevant fluid overload. An adjusted impedance at first postoperative day shorter than the best respective threshold was associated to longer MV (7.4 times), ICU stay (4.7 times) and hospital stay (5.6 times). A significant change in impedance and phase angle was documented throughout the observation days (p < 0.001), without returning to the baseline value. The co-existence of low impedance and high plasma osmolarity increased significantly the risk of incurring the study outcomes. CONCLUSIONS: In patients with cardiac surgery-induced fluid overload, recovery to baseline conditions occurs slowly. A relevant early fluid overload should be considered predictive for longer time of MV, ICU and total hospital stay.

Effect of General Anesthesia Versus Conscious Sedation/Local Anesthesia on the Outcome of Patients with Minor Stroke and Isolated M2 Occlusion Undergoing Immediate Thrombectomy: A Retrospective Multicenter Matched Analysis.

BACKGROUND: This study investigates the impact of general anesthesia (GA) versus conscious sedation/local anesthesia (CS/LA) on the outcome of patients with minor stroke and isolated M2 occlusion undergoing immediate mechanical thrombectomy (iMT). METHODS: The databases of 16 comprehensive stroke centers were retrospectively screened for consecutive patients with isolated M2 occlusion and a baseline National Institutes of Health Stroke Scale score ≤5 who received iMT. Propensity score matching was used to estimate the effect of GA versus CS/LA on clinical outcomes and procedure-related adverse events. The primary outcome measure was a 90-day modified Rankin Scale (mRS) score of 0-1. Secondary outcome measures were a 90-day mRS score of 0-2 and all-cause mortality, successful reperfusion, procedural-related symptomatic subarachnoid hemorrhage, intraprocedural dissections, and new territory embolism. RESULTS: Of the 172 patients who were selected, 55 received GA and 117 CS/LA. After propensity score matching, 47 pairs of patients were available for analysis. We found no significant differences in clinical outcome, rates of efficient reperfusion, and procedural-related complications between patients receiving GA or LA/CS (mRS score 0-1, P = 0.815; mRS score 0-2, P = 0.401; all-cause mortality, P = 0.408; modified Treatment in Cerebral Infarction score 2b-3, P = 0.374; symptomatic subarachnoid hemorrhage, P = 0.082; intraprocedural dissection, P = 0.408; new territory embolism, P = 0.462). CONCLUSIONS: In patients with minor stroke and isolated M2 occlusion undergoing iMT, the type of anesthesia does not affect clinical outcome or the rate of procedural-related complications. Our results agree with recent data showing no benefit of one specific anesthesiologic procedure over the other and confirm their generalizability also to patients with minor baseline symptoms.

Predictors of parenchymal hematoma and clinical outcome after mechanical thrombectomy in patients with large ischemic core due to large vessel occlusion: a retrospective multicenter study.

BACKGROUND: The aim of our study was to find predictors of parenchymal hematoma (PH) and clinical outcome after mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) and baseline large infarct. METHODS: The databases of 16 stroke centers were retrospectively screened for patients with anterior circulation LVO and baseline Alberta Stroke Program Early CT Score (ASPECTS) ≤5 that received MT. Procedural parameters, including the number of passes during first and second technique of MT, were recorded. Outcome measures were occurrence of PH type 2 and any type of PH after MT, and the 90-day modified Rankin Scale (mRS) score of 0-3 and 0-2. RESULTS: In total, 408 patients were available for analysis. A higher number of passes in the second technique was predictive of PH type 2 (odds ratio (OR) - 3.204, 95% confidence interval (CI) 1.140 to 9.005), whereas procedure conducted under general anesthesia was associated with lower risk (OR 0.127, 95% CI 0.002 to 0.808). The modified thrombolysis in cerebral infarction grade 2c-3 was associated with the mRS score 0-3 (OR 3.373, 95% CI 1.891 to 6.017), whereas occurrence of PH type 2 was predictive of unfavorable outcome (OR 0.221, 95% CI 0.063 to 0.773). Similar results were found for the mRS score 0-2 outcome measure. CONCLUSION: In patients with large ischemic core, a higher number of passes during MT and procedure not conducted under general anesthesia are associated with increased rate of PH type 2, that negatively impact the clinical outcome. Our data outline a delicate balance between the need of a complete recanalization and the risk of PH following MT.

Lithobiontic recolonization following cleaning and preservative treatments on the rock engravings of Valle Camonica, Italy: A 54-months monitoring.

Both the indirect control of microclimate conditions and the direct application of preservative products to contrast stone bioreceptivity may contribute to limit lithobiontic recolonization of cultural heritage surfaces after cleaning interventions. However, the priority deserved by these different preventive approaches has still been poorly evaluated, particularly in outdoor environments. This work dealt with the engraved sandstone surfaces of the National Park of Rock Engravings of Naquane (Italy, UNESCO WHS), widely colonized by lichens, mosses and a dark cyanobacterial biofilm, and thus requiring frequent cleaning interventions to preserve their legibility for visitors and scholars. In particular, post-cleaning recolonization by the different lithobionts was seasonally monitored along 54 months in different zones of an engraved outcrop, primarily differing in levels of shading, on parcels exposed to nine different conservative treatments. These included (or not) a pre-cleaning devitalization of lithobionts and the post-cleaning application of biocidal (benzalkonium chloride, plant essential oils, usnic acid) and other restoration products (nanocrystalline anatase, polysiloxane-based water repellent, ethyl-silicate-based consolidant). The combination of surface image analyses, fluorimetric and colorimetric measurements showed that mosses and the cyanobacterial biofilm rapidly recolonized all the parcels in the more shaded zone, irrespective of conservative treatments. In the other areas, recolonization significantly differed depending on the treatment. The post-cleaning application of biocides determined the best results through two vegetative seasons, but only nanocrystalline anatase and the polysiloxane-based water repellent maintained the surfaces lighter than uncleaned controls along the whole monitoring period. Recolonization primarily proceeded by the uncleaned surfaces surrounding the parcels and, at least in the examined case of lichens, did not show substantial shifts in community composition, although some nitrophytic species increased their frequency. In conclusion, the effectiveness of preservative treatments to prevent a rapid recolonization of heritage stone surfaces appeared subordinate to the presence of microenvironmental conditions less favourable to lithobionts.

IV thrombolysis plus thrombectomy versus IV thrombolysis alone for minor stroke with anterior circulation large vessel occlusion from the IRETAS and Italian SITS-ISTR cohorts.

INTRODUCTION: The aim of this study was to compare the outcomes of patients treated with intravenous thrombolysis (IVT) <4.5 h after symptom onset plus mechanical thrombectomy (MT) <6 h with those treated with IVT alone <4.5 h for minor stroke (NIHSS ≤5) with large vessel occlusion (LVO) in the anterior circulation. PATIENTS AND METHODS: Patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analyzed. RESULTS: Among the patients with complete data on 24-h ICH type, 236 received IVT plus MT and 382 received IVT alone. IVT plus MT was significantly associated with unfavorable shift on 24-h ICH types (from no ICH to PH-2) (OR, 2.130; 95% CI, 1.173-3.868; p=0.013) and higher rate of PH (OR, 4.363; 95% CI, 1.579-12.055; p=0.005), sICH per ECASS II definition (OR, 5.527; 95% CI, 1.378-22.167; p=0.016), and sICH per NINDS definition (OR, 3.805; 95% CI, 1.310-11.046; p=0.014). Among the patients with complete data on 3-month mRS score, 226 received IVT plus MT and 262 received IVT alone. No significant difference was reported between IVT plus MT and IVT alone on mRS score 0-1 (72.1% versus 69.1%), mRS score 0-2 (79.6% versus 79%), and death (6.2% versus 6.1%). CONCLUSIONS: Compared with IVT alone, IVT plus MT was associated with unfavorable shift on 24-h ICH types and higher rate of 24-h PH and sICH in patients with minor stroke and LVO in the anterior circulation. However, no difference was reported between the groups on 3-month functional outcome measures.

Predictors for hemorrhagic transformation and cerebral edema in stroke patients with first-pass complete recanalization.

BACKGROUND: Predictors of radiological complications attributable to reperfusion injury remain unknown when baseline setting is optimal for endovascular treatment and procedural setting is the best in stroke patients with large vessel occlusion (LVO). AIMS: To identify clinical and radiological/procedural predictors for hemorrhagic transformation (HT) and cerebral edema (CED) at 24 hr in patients obtaining complete recanalization in one pass of thrombectomy for ischemic stroke ⩽ 6 h from symptom onset with intra-cranial anterior circulation LVO and ASPECTS ⩾ 6. METHODS: We conducted a cohort study on prospectively collected data from 1400 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. RESULTS: HT was reported in 248 (18%) patients and early CED was reported in 260 (19.2%) patients. In the logistic regression model including predictors from a first model with clinical variables and from a second model with radiological/procedural variables, diabetes mellitus (odds ratio (OR) = 1.832, 95% confidence interval (CI) = 1.201-2.795), higher National Institutes of Health Stroke Scale (NIHSS) (OR = 1.076, 95% CI = 1.044-1.110), lower Alberta Stroke Program Early CT (ASPECTS) (OR = 0.815, 95% CI = 0.694-0.957), and longer onset-to-groin time (OR = 1.005, 95% CI = 1.002-1.007) were predictors of HT, whereas general anesthesia was inversely associated with HT (OR = 0.540, 95% CI = 0.355-0.820). Higher NIHSS (OR = 1.049, 95% CI = 1.021-1.077), lower ASPECTS (OR = 0.700, 95% CI = 0.613-0.801), intravenous thrombolysis (OR = 1.464, 95% CI = 1.061-2.020), longer onset-to-groin time (OR = 1.002, 95% CI = 1.001-1.005), and longer procedure time (OR = 1.009, 95% CI = 1.004-1.015) were predictors of early CED. After repeating a fourth logistic regression model including also good collaterals, the same variables remained predictors for HT and/or early CED, except diabetes mellitus and thrombolysis, while good collaterals were inversely associated with early CED (OR = 0.385, 95% CI = 0.248-0.599). CONCLUSIONS: Higher NIHSS, lower ASPECTS, and longer onset-to-groin time were predictors for both HT and early CED. General anesthesia and good collaterals were inversely associated with HT and early CED, respectively. Longer procedure time was predictor of early CED.

Stroke with large vessel occlusion in the posterior circulation: IV thrombolysis plus thrombectomy versus IV thrombolysis alone.

Efficacy and safety of mechanical thrombectomy (MT) for stroke with posterior circulation large vessel occlusion (LVO) is still under debate. We aimed to compare the outcomes of stroke patients with posterior circulation LVO treated with intravenous thrombolysis (IVT) (< 4.5 h after symptom onset) plus MT < 6 h after symptom onset with those treated with IVT alone (< 4.5 h after symptom onset). Patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analysed. We identified 409 IRETAS patients treated with IVT plus MT and 384 SITS-ISTR patients treated with IVT alone. IVT plus MT was significantly associated with higher rate of sICH (ECASS II) compared with IVT alone (3.1 vs 1.9%; OR 3.984, 95% CI 1.014-15.815), while the two treatments did not differ significantly in 3-month mRS score ≤ 3 (64.3 vs 74.1%; OR 0.829, 95% CI 0.524-1.311). In 389 patients with isolated basilar artery (BA) occlusion, IVT plus MT was significantly associated with higher rate of any ICH compared with IVT alone (9.4 vs 7.4%; OR 4.131, 95% CI 1.215-14.040), while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with higher rate mRS score ≤ 2 (69.1 vs 52.1%; OR 2.692, 95% CI 1.064-6.811) and lower rate of death (13.8 vs 27.1%; OR 0.299, 95% CI 0.095-0.942) in patients with distal-segment BA occlusion, while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with lower rate of mRS score ≤ 3 (37.1 vs 53.3%; OR 0.137, 0.009-0.987), mRS score ≤ 1 (22.9 vs 53.3%; OR 0.066, 95% CI 0.006-0.764), mRS score ≤ 2 (34.3 vs 53.3%; OR 0.102, 95% CI 0.011-0.935), and higher rate of death (51.4 vs 40%; OR 16.244, 1.395-89.209) in patients with proximal-segment BA occlusion. Compared with IVT alone, IVT plus MT was significantly associated with higher rate of sICH per ECASS II definition in patients with stroke and posterior circulation LVO, while two treatment groups did not differ significantly in 3-month mRS score ≤ 3. IVT plus MT was associated with lower rate of mRS score ≤ 3 compared with IVT alone in patients with proximal-segment BA occlusion, whereas no significant difference was found between the two treatments in primary endpoints in patients isolated BA occlusion and in the other subgroups based on site occlusion.

Redox double-switch cancer theranostics through Pt(IV) functionalised manganese dioxide nanostructures.

Manganese dioxide (MnO2)-based nanostructures have emerged as promising tumour microenvironment (TME) responsive platforms. Herein, we used a one-pot reaction to prepare MnO2 nanostructures with Pt(IV) prodrugs as redox- (and thus TME-) responsive theranostics for cancer therapy, in which the Pt(IV) complexes act as prodrugs of cisplatin (Pt(II)), a clinical chemotherapeutic drug. The cytotoxicity of these MnO2-Pt(IV) probes was evaluated in two and three dimensional (2D and 3D) A549 cell models and found to be as effective as active drug cisplatin in 3D models. Moreover, MnO2-Pt(IV) nanoparticles exhibited strong off/ON magnetic resonance (MR) contrast in response to reducing agents, with the longitudinal relaxivity (r1) increasing 136-fold upon treatment with ascorbic acid. This off/ON MR switch was also observed in (2D and 3D) cells in vitro. In vivo MRI experiments revealed that the nanostructures induce a strong and long-lasting T1 signal enhancement upon intratumoral injection in A549 tumour-bearing mice. These results show the potential of MnO2-Pt(IV) NPs as redox responsive MR theranostics for cancer therapy.

Predictors for clinical and functional outcomes in stroke patients with first-pass complete recanalization after thrombectomy.

BACKGROUND AND PURPOSE: The aim was to identify baseline clinical and radiological/procedural predictors and 24-h radiological predictors for clinical and functional outcomes in stroke patients obtaining complete recanalization in one pass of mechanical thrombectomy (MT) in an optimal baseline and procedural setting. METHODS: A retrospective analysis was conducted of prospectively collected data from 924 stroke patients with anterior large vessel occlusion, Alberta Stroke Program Early Computed Tomography (ASPECT) score ≥6 and pre-stroke modified Rankin Scale score 0, who started MT ≤6 h from symptom onset and obtained first-pass complete recanalization. A first logistic regression model was performed to identify baseline clinical predictors and a second model to identify baseline radiological/procedural predictors. A third model including baseline clinical and radiological/procedural predictors was performed, and a fourth model including independent baseline predictors from the third model plus 24-h radiological variables (hemorrhagic transformation [HT] and cerebral edema [CED]). RESULTS: In the fourth model, higher National Institutes of Health Stroke Scale (NIHSS) score (odds ratio [OR] 1.089) and higher ASPECT score (OR 1.292) were predictors of early neurological improvement (ENI) (NIHSS score ≤4 points from baseline or NIHSS score of 0 at 24 h), whereas older age (OR 0.973), longer procedure time (OR 0.990), HT (OR 0.272) and CED (OR 0.569) were inversely associated with ENI. Older age (OR 0.970), diabetes mellitus (OR 0.456), higher NIHSS score (OR 0.886), general anesthesia (OR 0.454), longer onset-to-groin time (OR 0.996), HT (OR 0.340) and CED (OR 0.361) were inversely associated with 3-month excellent functional outcome (mRS score 0-1), whereas higher ASPECT score (OR 1.294) was a predictor of excellent outcome. CONCLUSIONS: Higher NIHSS score was a predictor of ENI but inversely associated with 3-month excellent outcome. Older age, HT and CED were inversely associated with both good outcomes.

Mechanical thrombectomy in patients with heart failure: the Italian registry of Endovascular Treatment in Acute Stroke.

BACKGROUND: Heart failure (HF) is the second most important cardiac risk factor for stroke after atrial fibrillation (AF). Few data are available on mechanical thrombectomy (MT) in acute ischemic stroke (AIS) patients with HF. METHODS: The source of data is the multicentre Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS). All AIS patients ≥ 18 years receiving MT were categorised in two groups: HF and no-HF. Baseline clinical and neuroradiological findings on admission were analysed. RESULTS: Of 8924 patients, 642 (7.2%) had HF. Compared to the no-HF group, HF patients had higher prevalence of cardiovascular risk factors. Rate of complete recanalisation (TICI 2b-3) was 76.9% in HF vs 78.1% in no-HF group (p = 0.481). Rate of symptomatic intracerebral haemorrhage at 24-h non-contrast computed tomography (NCCT) was 7.6% in HF vs 8.3% in no-HF patients (p = 0.520). At 3 months, 36.4% of HF patients and 48.2% of no-HF patients (p < 0.001) had mRS 0-2, and mortality was, respectively, 30.7% and 18.5% (p < 0.001). In multivariate logistic regression, HF was independently associated with mortality at 3 months (OR 1.53, 1.24-1.88 95% CI, p < 0.001). In multivariate ordinal regression, HF patients had a probability of transitioning to a higher mRS level of 1.23 (1.05-1.44 95% CI, p = 0.012). The propensity score analysis of two groups matched for age, sex, and NIHSS at admission yielded the same results. CONCLUSION: MT is safe and effective in HF patients with AIS. Patients with HF and AIS suffered from higher 3-month mortality and unfavourable outcome regardless of acute treatments.

Boosting intracellular sodium selectively kills hepatocarcinoma cells and induces hepatocellular carcinoma tumor shrinkage in mice.

Pharmacological treatments for advanced hepatocellular carcinoma (HCC) have a partial efficacy. Augmented Na+ content and water retention are observed in human cancers and offer unexplored targets for anticancer therapies. Na+ levels are evaluated upon treatments with the antibiotic cation ionophore Monensin by fluorimetry, ICP-MS, 23Na-MRI, NMR relaxometry, confocal or time-lapse analysis related to energy production, water fluxes and cell death, employing both murine and human HCC cell lines, primary murine hepatocytes, or HCC allografts in NSG mice. Na+ levels of HCC cells and tissue are 8-10 times higher than that of healthy hepatocytes and livers. Monensin further increases Na+ levels in HCC cells and in HCC allografts but not in primary hepatocytes and in normal hepatic and extrahepatic tissue. The Na+ increase is associated with energy depletion, mitochondrial Na+ load and inhibition of O2 consumption. The Na+ increase causes an enhancement of the intracellular water lifetime and death of HCC cells, and a regression and necrosis of allograft tumors, without affecting the proliferating activity of either HCCs or healthy tissues. These observations indicate that HCC cells are, unlike healthy cells, energetically incapable of compensating and surviving a pharmacologically induced Na+ load, highlighting Na+ homeostasis as druggable target for HCC therapy.

Greater Gastrocnemius Muscle Hypertrophy After Partial Range of Motion Training Performed at Long Muscle Lengths.

ABSTRACT: Kassiano, W, Costa, B, Kunevaliki, G, Soares, D, Zacarias, G, Manske, I, Takaki, Y, Ruggiero, MF, Stavinski, N, Francsuel, J, Tricoli, I, Carneiro, MAS, and Cyrino, ES. Greater gastrocnemius muscle hypertrophy after partial range of motion training performed at long muscle lengths. J Strength Cond Res 37(9): 1746-1753, 2023-Whether there is an optimal range of motion (ROM) to induce muscle hypertrophy remains elusive, especially for gastrocnemius. This study aimed to compare the changes in gastrocnemius muscle thickness between calf raise exercise performed with full ROM (FULL ROM ), partial ROM performed in the initial (INITIAL ROM ), and final (FINAL ROM ) portions of the ROM. Forty-two young women performed a calf training program for 8 weeks, 3 days·week -1 , with differences in the calf raise ROM configuration. The calf raise exercise was performed in a pin-loaded, horizontal, leg-press machine, in 3 sets of 15-20 repetition maximum. The subjects were randomly assigned to 1 of the 3 groups: FULL ROM (ankle: -25° to +25°), INITIAL ROM (ankle: -25° to 0°), and FINAL ROM (ankle: 0° to +25°), where 0° was defined as an angle of 90° of the foot with the tibia. The muscle thickness measurements of medial and lateral gastrocnemius were taken by means of B-mode ultrasound. INITIAL ROM elicited greater medial gastrocnemius increases than FULL ROM and FINAL ROM (INITIAL ROM = +15.2% vs. FULL ROM = +6.7% and FINAL ROM = +3.4%; p ≤ 0.009). Furthermore, INITIAL ROM elicited greater lateral gastrocnemius increases than FINAL ROM (INITIAL ROM = +14.9% vs. FINAL ROM = +6.2%; p < 0.024) but did not significantly differ from FULL ROM (FULL ROM = +7.3%; p = 0.060). The current results suggest that calf training performed at longer muscle lengths may optimize gastrocnemius muscle hypertrophy in young women. Therefore, when prescribing hypertrophy-oriented training, the inclusion of the calf raise exercise performed with partial ROM in the initial portion of the excursion should be considered.

Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis.

Introduction: Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke. Patients and methods: We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group). We compared groups for symptomatic intracranial hemorrhage (sICH, main outcome), any brain hemorrhage, good functional outcome (mRS 0-2 at 3 months), and death. The systematic review followed a predefined protocol (CRD42017060274), and odds ratio (OR) meta-analysis was implemented to compare groups. Results: Thirty-nine patients in dabigatran-reversal group and 300 matched controls were included. Reversal was associated with a non-significant increase in sICH (10.3% vs 6%, aOR = 1.32, 95% CI = 0.39-4.52), death (17.9% vs 10%, aOR = 0.77, 95% CI = 0.12-4.93) and good functional outcome (64.1% vs 52.8%, aOR = 1.41, 95% CI = 0.63-3.19). No hemorrhagic events or deaths were registered in no-reversal group (n = 12). Pooling data from 3 studies after systematic review (n = 1879), reversal carried a non-significant trend for sICH (OR = 1.53, 95% CI = 0.67-3.50), death (OR = 1.53, 95% CI = 0.73-3.24) and good functional outcome (OR = 2.46, 95% CI = 0.85-7.16). Discussion and conclusion: People treated with reperfusion strategies after dabigatran reversal with idarucizumab seem to have a marginal increase in the risk of sICH but comparable functional recovery to matched patients with stroke. Further studies are needed to define treatment cost-effectiveness and potential thresholds in plasma dabigatran concentration for reversal.

Early neurological deterioration in patients with minor stroke due to isolated M2 occlusion undergoing medical management: a retrospective multicenter study.

BACKGROUND: Patients with minor stroke and M2 occlusion undergoing best medical management (BMM) may face early neurological deterioration (END) that can lead to poor long-term outcome. In case of END, rescue mechanical thrombectomy (rMT) seems beneficial. Our study aimed to define factors relevant to clinical outcome in patients undergoing BMM with the possibility of rMT on END, and find predictors of END. METHODS: Patients with M2 occlusion and a baseline National Institutes of Health Stroke Scale (NIHSS) score≤5 that received either BMM only or rMT on END after BMM were extracted from the databases of 16 comprehensive stroke centers. Clinical outcome measures were a 90-day modified Rankin Scale (mRS) score of 0-1 or 0-2, and occurrence of END. RESULTS: Among 10 169 consecutive patients with large vessel occlusion admitted between 2016 and 2021, 208 patients were available for analysis. END was reported in 87 patients that were therefore all subjected to rMT. In a logistic regression model, END (OR 3.386, 95% CI 1.428 to 8.032), baseline NIHSS score (OR 1.362, 95% CI 1.004 to 1.848) and a pre-event mRS score=1 (OR 3.226, 95% CI 1.229 to 8.465) were associated with unfavorable outcome. In patients with END, successful rMT was associated with favorable outcome (OR 4.549, 95% CI 1.098 to 18.851). Among baseline clinical and neuroradiological features, presence of atrial fibrillation was a predictor of END (OR 3.547, 95% CI 1.014 to 12.406). CONCLUSION: Patients with minor stroke due to M2 occlusion and atrial fibrillation should be closely monitored for possible worsening during BMM and, in this case, promptly considered for rMT.

Mechanical thrombectomy in minor stroke due to isolated M2 occlusion: a multicenter retrospective matched analysis.

BACKGROUND: The purpose of this study was to evaluate the effectiveness of mechanical thrombectomy (MT) in patients with isolated M2 occlusion and minor symptoms and identify possible baseline predictors of clinical outcome. METHODS: The databases of 16 high-volume stroke centers were retrospectively screened for consecutive patients with isolated M2 occlusion and a baseline National Institutes of Health Stroke Scale (NIHSS) score ≤5 who received either early MT (eMT) or best medical management (BMM) with the possibility of rescue MT (rMT) on early neurological worsening. Because our patients were not randomized, we used propensity score matching (PSM) to estimate the treatment effect of eMT compared with the BMM/rMT. The primary clinical outcome measure was a 90-day modified Rankin Scale score of 0-1. RESULTS: 388 patients were initially selected and, after PSM, 100 pairs of patients receiving eMT or BMM/rMT were available for analysis. We found no significant differences in clinical outcome and in safety measures between patients receiving eMT or BMM/rMT. Similar results were also observed after comparison between eMT and rMT. Concerning baseline predicting factors of outcome, the involvement of the M2 inferior branch was associated with a favorable outcome. CONCLUSION: Our multicenter retrospective analysis has shown no benefit of eMT in minor stroke patients with isolated M2 occlusion over a more conservative therapeutic approach. Although our results must be viewed with caution, in these patients it appears reasonable to consider BMM as the first option and rMT in the presence of early neurological deterioration.