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BackgroundThe 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.MethodsThe 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.Results388 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.ConclusionOur 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.

BackgroundThe Woven EndoBridge (WEB) device is a novel intrasaccular flow disruptor tailored for bifurcation aneurysms. We aim to describe the degree of aneurysm occlusion at the latest follow-up, and the rate of complications of aneurysms treated with the WEB device stratified according to rupture status.MethodsOur data were taken from the WorldWideWeb Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups: ruptured and unruptured. We compared clinical and radiologic outcomes of both groups. Propensity score matching (PSM) was done to match according to age, gender, bifurcation, location, prior treatment, neck, height, dome width, daughter sac, incorporated branch, pretreatment antiplatelets, and last imaging follow-up.ResultsThe study included 676 patients with 691 intracranial aneurysms (529 unruptured and 162 ruptured) treated with the WEB device. The PSM analysis had 55 pairs. In both the unmatched (85.8% vs 84.3%, p=0.692) and matched (94.4% vs 83.3%, p=0.066) cohorts there was no significant difference in the adequate occlusion rate at the last follow-up. Likewise, there were no significant differences in both ischemic and hemorrhagic complications between the two groups. There was no documented aneurysm rebleeding after WEB device implantation.ConclusionThere was no significant difference in both the radiologic outcomes and complications between unruptured and ruptured aneurysms. Our findings support the feasibility of treatment of ruptured aneurysms with the WEB device.

BackgroundThe Woven EndoBridge (WEB) device has Food and Drug Administration approval for treatment of wide-necked intracranial bifurcation aneurysms. The WEB device has been shown to result in adequate occlusion in bifurcation aneurysms overall, but its usefulness in the individual bifurcation locations has been evaluated separately only in few case series, which were limited by small sample sizes.ObjectiveTo compare angiographic and clinical outcomes after treatment of bifurcation aneurysms at various locations, including anterior communicating artery (AComA), anterior cerebral artery (ACA) bifurcation distal to AComA, basilar tip, internal carotid artery (ICA) bifurcation, and middle cerebral artery (MCA) bifurcation aneurysms using the WEB device.MethodsA retrospective cohort analysis was conducted at 22 academic institutions worldwide to compare treatment outcomes of patients with intracranial bifurcation aneurysms using the WEB device. Data include patient and aneurysm characteristics, procedural details, angiographic and functional outcomes, and complications.ResultsA total of 572 aneurysms were included. MCA (36%), AComA (35.7%), and basilar tip (18.9%) aneurysms were most common. The rate of adequate aneurysm occlusion was significantly higher for basilar tip (91.6%) and ICA bifurcation (96.7%) aneurysms and lower for ACA bifurcation (71.4%) and AComA (80.6%) aneurysms (p=0.04).ConclusionTo our knowledge, this is the most extensive study to date that compares the treatment of different intracranial bifurcation aneurysms using the WEB device. Basilar tip and ICA bifurcation aneurysms showed significantly higher rates of aneurysm occlusion than other locations.

No significant difference in the angiographic and clinical outcomes was observed for the treatment of sidewall versus bifurcation intracranial aneurysms with use of Woven EndoBridge.

AimsAccording to The Cancer Genome Atlas (TCGA), around 9% of bladder carcinomas usually show abnormalities of the murine double minute 2 (MDM2) gene, but a few studies have been investigated them. We profiled MDM2 gene amplification in a series of urothelial carcinomas (UC) considering the molecular subtypes and expression of programmed death ligand 1 (PD-L1).Methods117 patients with muscle-invasive UC (pT2-3) without (N0) or with (N+) lymph-node metastases were revised. Only cases with availability of in toto specimens and follow-up were studied. Tissue microarray was built. p53, ER, RB1, GATA-3, CK20, CK5/6, CD44 and PD-L1 (clone sp263) immunoexpression was evaluated. Fluorescent in situ hybridisation was assessed by using the HER-2/neu, FGFR-3, CDKN2A and MDM2 probes. True (ratio 12q/CEP12 >2) MDM2 gene amplification was distinguished from polyploidy/gains (ratio <2, absolute copy number of MDM-2 >2). MDM2 and PD-L1 values were correlated to the TCGA molecular phenotypes. Statistical analysis was performed.Results6/50 (12%) cases (5 N0 and 1 N+) were amplified for MDM2 without matching to molecular phenotypes. Of 50, 14 (37%) cases expressed PD-L1 at 1% cut-off; 3/50 (9%) at >50% cut-off; of these, 2 cases on side of neoplasia among inflammatory cells. Only one out of six (17%) cases amplified for MDM2 showed expression (>50% cut-off) of PD-L1. MDM2 amplification was independent to all documented profiles (k test=0.3) and was prevalent in recurrent UC.ConclusionMDM2 amplification has been seen in both PD-L1 positive and negative muscle-invasive bladder UC independently from the TCGA molecular phenotypes. MDM2 and PD-L1 might be assessed in order to predict a better response to combo/single targeted therapies.

Objective A systematic review and meta-analysis of Autologous Matrix-Induced Chondrogenesis (AMIC®) outcomes for grade III/IV chondral and osteochondral lesions of the knee treated with Chondro-Gide®.Design Studies with a minimum follow-up of 1 year providing clinical results of AMIC repair in the knee were included based on PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Methodological quality was assessed by the modified Coleman Methodology Score (mCMS). The meta-analysis was comparing pain VAS (Visual Analog Scale), Lysholm score, and IKDC score (International Knee Documentation Committee) between baseline and follow-up after 1 or 2 years and after >3 years.Results Twelve studies (375 patients) were included. The mCMS demonstrated a suboptimal study design (ranking between 52 and 80). The mean age was 36.2 years (14-70 years). The mean defect size was 4.24 cm2(0.8-22 cm2). The results from the random effects model indicated a clinically significant (P< 0.05) improvement of pain VAS from baseline to follow-up at year 1 to 2 of −4.02(confidence interval −4.37; −3.67), still significant after 3 years. Lysholm score at year 1 or 2 improved significantly and remained highly significant after 3 years. IKDC score showed highly significant improvement of 32.61 between 1 and 2 years versus baseline values maintained after 3 years.Conclusions The AMIC procedure significantly improved the clinical status and functional scoring versus preoperative values. Evidence was obtained in a non-selected patient population, corresponding to real-life treatment of knee chondral and osteochondral defects. The evidence is sufficient to recommend AMIC in this indication.

The rapid growth of available wearable technologies, particularly in the healthcare sector, has ushered in a new era of digital health. This progress has introduced new possibilities for the monitoring of vital signs, including breathing rate (BR). BR is a crucial health parameter used to assess an individual's overall well-being; specifically, it can be considered a precise indicator of pathological conditions and stressors. The aim of this study is to conduct a metrological characterization of one of the most widely used BR sensors for the measurement of BR (i.e., Zephyr BioHarness 3.0), comparing it to a BR gold standard monitor (i.e., a spirometer), in determined test conditions, including both natural and defined BR patterns. Additionally, the Monte Carlo method (MCM) was applied to evaluate the propagation of the measurement uncertainty in the identification of the peaks of respiratory signal, used to calculate BR. Results reveal that the Zephyr BioHarness 3.0 sensor provides highly accurate BR measurements, with a precision of ±1 bpm. Bland-Altman analysis indicates a 95 % confidence interval of [-2; 3] bpm, demonstrating a close agreement with the reference instrument. The Pearson's correlation coefficient of 0.95 further validates the linear correlation between the reference/test measurements. The simulation based on MCM provides an expanded uncertainty of ±2 bpm (coverage factor k = 2) in BR estimation due to the uncertainty in the peaks identification (compatible with the accuracy provided by the manufacturer). These results highlight the Zephyr BioHarness 3.0 sensor reliability for BR monitoring while emphasizing the significance of accounting for different disturbing factors, e.g., uncertainty in peak detection during data analysis, also to provide a rigorous level of confidence in the measurement results, hence being able to properly interpret them in biomedical applications.

Introduction: Long-term use of bisphosphonates (BPs) has been associated with a specific type of tensile side femoral stress fracture known as Atypical Femoral Fracture (AFF). Theoretically periprosthetic femoral fractures (PFF) should be excluded from the diagnosis of AFF. However, emerging evidence correlates prolonged BPs use with the occurrence of a type of PFF with an atypical pattern (atypical PFF, APFF). The aim of the present study is to report 3 cases of APFF treated at a single centre.Methods: Clinical and radiographic records of PFF that occurred between January 2016 and August 2018 were retrospectively reviewed. All patients meeting the American Society for Bone and Mineral Research (ASBMR) criteria for definition of PFF were included. Management strategies for APFF and patient outcomes, including fracture healing and hip function (assessed by the Oxford Hip Score [OHS]) were collected.Results: 3 patients in the study period were identified as APFF (1 incomplete, 2 complete). All patients were females with a mean age of 83.3?years. All patients were treated with lateral plating. The application of a contralateral strut allograft resulted in fracture healing in cases of complete fractures. Mean OHS at final follow-up was 34.3.Conclusions: Despite occurring around a hip stem like PFF, APFF had peculiar clinical and radiographic features, making them more similar to AFF. Therefore, the orthopaedic surgeon should also consider the natural history and healing problems associated with AFF prior in order to choose the most appropriate management for APFF.

Atezolizumab can induce sustained responses in metastatic urothelial carcinoma. We report the results of IMvigor130, a phase 3 trial that compared atezolizumab with or without platinum-based chemotherapy versus placebo plus platinum-based chemotherapy in first-line metastatic urothelial carcinoma.

Supplemental Digital Content is available in the text.

Hip fractures are severe conditions with a high morbidity and mortality, especially when the diagnosis is delayed, and if formulated over 30 days after the injury, is termed a ‘neglected femoral neck fracture’ (NFNF).Cerebral palsy (CP) is probably one of the major risk factors for NFNF in Western countries, mainly because of both cognitive and motor impairments. However, considering the high prevalence of fractures in these patients, the incidence of NFNF in this population is probably underestimated, and this condition might result in persistent hip or abdominal pain.Several techniques are available for the treatment of NFNF (i.e. muscle pedicle bone graft, fixation with fibular graft, valgisation osteotomy), but most of them could affect motor function.Motor function must be preserved for as long as possible, in order to enhance the quality of life of CP patients.After discussing published NFNF cases in CP patients and available treatment options, a practical approach is proposed to facilitate the orthopaedic surgeon to both early identify and appropriately manage these challenging fractures.Cite this article: EFORT Open Rev2020;5:58-64. DOI: 10.1302/2058-5241.5.190019

Supplemental Digital Content is available in the text.Immune-related adverse events (irAEs) are autoimmune-toxic effects associated with immune checkpoint inhibitors (ICIs) used for the treatment of advanced solid tumors. We performed a systematic review and meta-analysis of the published literature to assess the outcome for cancer patients treated with ICIs who develop irAEs. Two independent reviewers selected prospective or retrospective studies from PubMed, EMBASE, and the Cochrane Library database from their inception to November 2018. Data were pooled using hazard ratios (HRs) for overall survival or progression-free survival or odds ratio for overall response rate of irAEs versus no irAEs according to fixed or random-effect model. HRs for OS (the primary outcome measure) were pooled to provide an aggregate value. A total of 30 studies that included a total of 4324 patients treated with ICIs were selected. Patients who developed irAEs presented a reduced risk of death [HR=0.49, 95% confidence interval (CI): 0.38–0.62; P<0.001]. Similarly, the occurrence of irAEs was associated with a reduced risk of progression (HR=0.51, 95% CI: 0.42–0.64; P<0.001). The odds of response was 4.56 (95% CI: 3.72–5.59; P<0.001). In patients treated with ICIs, irAEs predict survival and response. Although this correlation cannot be fully explained, it may be related to the strongest T-cell activation.

BackgroundAlthough accumulating evidence has demonstrated the benefit of mechanical thrombectomy (MT) in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS), it is still unclear how workflow metrics impact the clinical outcomes of this subgroup of patients.MethodsPatients with acute stroke and diffusion-weighted imaging (DWI) ASPECTS ≤5 at baseline, who underwent MT within 6 hours of symptoms onset, were included from a prospectively maintained national multicentric registry between January 1, 2012 to August 31, 2017. The degree of disability was assessed by the modified Rankin Scale (mRS) at 90 days. The primary outcome was functional independence defined as mRS 0 to 2 at 90 days.ResultsThe study included 291 patients with baseline DWI-ASPECTS ≤5. Good outcome was achieved in 82 (28.2%) patients, and 104 (35.7%) patients died within 90 days. Successful reperfusion (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3) rate was 75.3%, and median onset to recanalization (OTR) time was 2 268min. Among time-related variables, OTR emerged as the strongest predictor of primary outcome (adjusted OR for every 60 min 0.59, 95% CI 0.44 to 0.77; p<0.001). mTICI 2c-3 independently predicted a good outcome (adjusted OR 1.91, 95% CI 1.004 to 3.6; p=0.049) along with age and baseline DWI-ASPECTS. Recanalization status failed to significantly impact outcome in the DWI-ASPECTS 0–3 subpopulation.ConclusionsNear complete reperfusion (mTICI 2c-3) and OTR are the strongest modifiable outcome predictors in patients with DWI-ASPECTS ≤5 treated with MT.

In light of the predicted shortage of surgeons, attrition from surgical residency is a significant problem. Prior data have shown that those who are happier are more productive, and those who are less well have higher rates of absenteeism. This study sought to identify the role of social belonging and its relationship to well-being and risk of attrition.