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Context: Non-syndromic cleft lip/palate (NSCL/P) is a congenital anomaly with significant medical, psychological and social ramifications. There is sufficient evidence to hypothesize that locus for this condition can be identified by candidate genes. Aims: The aim of this study is to amplify the chosen region (799 G >T) of MSX 1 gene, investigate the degree of association and perform a mutation research from Raichur cleft lip and palate patient sample. Settings and Design: Case history and clinical examination of the patient were recorded to rule. Written consent was obtained from patients and controls for in vivo study. Study was designed in four steps as follows: Collection of a blood sampleGenomic deoxyribonucleic acid (DNA) extractionPolymerase chain reaction (PCR)Restriction fragment length polymorphism (RFLP). Materials and Methods: Blood samples were collected from 50 subjects having NSCL/P and 50 controls. Genomic DNA was extracted, PCR and RFLP was performed for digestion products that were evaluated. Statistical Analysis: Chi-square test with P value at 95% confidence intervals. Results: The results showed a positive correlation between MSX 1 799 G >T gene variant and NSCL/P patients in Raichur patients. Conclusions: From a genetically diverse etiology MSX 1 799 G >T gene variant may be a good screening marker for NSCL/P in Raichur patients.

Background: Robust venous outflow (VO) profiles, measured by degree of venous opacification on pre-thrombectomy CT angiography (CTA) studies, are strongly correlated with favorable outcomes in patients with large vessel occlusion acute ischemic stroke treated by thrombectomy. However, VO measurements are laborious and require neuroimaging expertise., Objective: To develop a semi-automated method to measure VO using CTA and CT perfusion imaging studies., Methods: We developed a graphical interface using The Visualization Toolkit, allowing for voxel selection at the confluence and bilateral internal cerebral veins on CTA along with arterial input functions (AIFs) from both internal carotid arteries. We extracted concentration-time curves from the CT perfusion study at the corresponding locations associated with AIF and venous output function (VOF). Outcome analyses were primarily conducted by the Mann-Whitney U and Jonckheere-Terpstra tests., Results: Segmentation at the pre-selected AIF and VOF locations was performed on a sample of 97 patients. 65 patients had favorable VO (VO+) and 32 patients had unfavorable VO (VO-). VO+ patients were found to have a significantly shorter VOF time to peak (8.26; 95% CI 7.07 to 10.34) than VO- patients (9.44; 95% CI 8.61 to 10.91), P=0.007. No significant difference was found in VOF curve width and the difference in time between AIF and VOF peaks., Conclusions: Time to peak of VOF at the confluence of sinuses was significantly associated with manually scored venous outflow. Further studies should aim to understand better the association between arterial inflow and venous outflow, and capture quantitative metrics of venous outflow at other locations., Competing Interests: Competing interests: GA, NY, MM, TDF, MGL have no relevant relationships to disclose. SC discloses equity and consulting for iSchemaView. GWA discloses equity and consulting for iSchemaView and consulting for Genentech. JF discloses grants and personal fees from Acandis, Cerenovus, MicroVention,Medtronic, and Stryker; grants from Route 92; and personal fees from Phenox and Penumbra outside of the submitted work. JJH discloses consulting for Medtronic and MicroVention and membership of the medical and scientific advisory board for iSchemaView., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Deep venous outflow (VO) may be an important surrogate marker of collateral blood flow in acute ischemic stroke patients with a large vessel occlusion (AIS-LVO). Researchers have yet to determine the relationship between deep VO status in late-window patients and imaging measures of collaterals, which are key in preserving tissue., Materials and Methods: We performed a multicenter retrospective cohort study on a subset of DEFUSE 3 patients recruited across 38 centers between May 2016 and May 2017 who underwent successful thrombectomy revascularization. Internal cerebral vein opacification was scored on a scale of 0-2. This metric was added to the cortical vein opacification score to derive the comprehensive VO (CVO) score from 0 to 8. Patients were stratified by favorable (ICV+) and unfavorable (ICV-) ICV scores, and similarly CVO+ and CVO-. Analyses comparing outcomes were primarily conducted by Mann-Whitney U and χ 2 tests., Results: Forty-five patients from DEFUSE 3 were scored and dichotomized into CVO+, CVO-, ICV+, and ICV- categories, with comparable demographics. Hypoperfusion intensity ratio, a marker of tissue level collaterals, was significantly worse in the ICV- and CVO- groups (p = 0.005). ICV- alone was also associated with a larger perfusion lesion (138 ml vs 87 ml; p = 0.023). No significant differences were noted in functional and safety outcomes., Conclusions: Impaired deep venous drainage alone may be a marker of poor tissue level collaterals and a greater degree of affected tissue in AIS-LVO patients presenting in the late-window who subsequently undergo successful revascularization., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.C. discloses equity and consulting for iSchemaView. G.W.A. discloses equity and consulting for iSchemaView and consulting for Genentech. J.F. discloses grants and personal fees from Acandis, Cerenovus, MicroVention,Medtronic, and Stryker, grants from Route 92, and personal fees from Phenox and Penumbra outside of the submitted work. J.J.H. discloses consulting for Medtronic and MicroVention and membership of the medical and scientific advisory board for iSchemaView.

Nanoparticle-mediated mRNA delivery has emerged as a promising therapeutic modality, but its growth is still limited by the discovery and optimization of effective and well-tolerated delivery strategies. Lipid nanoparticles containing charged or ionizable lipids are an emerging standard for in vivo mRNA delivery, so creating facile, tunable strategies to synthesize these key lipid-like molecules is essential to advance the field. Here, we generate a library of N-substituted glycine oligomers, peptoids, and undertake a multistage down-selection process to identify lead candidate peptoids as the ionizable component in our Nutshell nanoparticle platform. First, we identify a promising peptoid structural motif by clustering a library of >200 molecules based on predicted physical properties and evaluate members of each cluster for reporter gene expression in vivo. Then, the lead peptoid motif is optimized using design of experiments methodology to explore variations on the charged and lipophilic portions of the peptoid, facilitating the discovery of trends between structural elements and nanoparticle properties. We further demonstrate that peptoid-based Nutshells leads to expression of therapeutically relevant levels of an anti-respiratory syncytial virus antibody in mice with minimal tolerability concerns or induced immune responses compared to benchmark ionizable lipid, DLin-MC3-DMA. Through this work, we present peptoid-based nanoparticles as a tunable delivery platform that can be optimized toward a range of therapeutic programs.

Background: High-quality evidence exists for mechanical thrombectomy (MT) treatment of acute ischemic stroke (AIS) due to large vessel occlusion of the anterior circulation (AC-LVO). The evidence for MT treatment of posterior circulation large vessel occlusion (PC-LVO) is weaker, largely drawn from lower quality studies specific to PC-LVO and extrapolated from findings in AC-LVO, and ambiguous with regards to technical success. We performed a systematic review and meta-analysis to compare the technical success and functional outcomes of MT in PC-LVO versus AC-LVO patients., Methods: We identified comparative studies reporting on patients treated with MT in AC-LVO versus PC-LVO. The primary outcome of interest was thrombolysis in cerebral infarction (TICI) ≥ 2b. Secondary outcomes included rates of TICI 3, 90-day functional independence, first-pass-effect, average number of passes, and 90-day mortality. A separate random effects model was fit for each outcome measure., Results: Twenty studies with 12,911 patients, 11,299 (87.5%) in the AC-LVO arm and 1612 (12.5%) in the PC-LVO arm, were included. AC-LVO and PC-LVO patients had comparable rates of successful recanalization [OR = 1.02 [95% CI: 0.79-1.33], p  = 0.848). However, the AC-LVO group had greater odds of 90-day functional independence (OR = 1.26 [95% CI: 1.00; 1.59], p  = 0.050) and lower odds of 90-day mortality (OR = 0.58 [95% CI: 0.43; 0.79], p  = 0.002)., Conclusions: MT achieves similar rates of recanalization with a similar safety profile in PC-LVO and AC-LVO patients. Patients with PC-LVO are less likely to achieve functional independence after MT. Future studies should identify PC-LVO patients who are likely to achieve favourable functional outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JMP works for and holds equity in Nested Knowledge, Inc., and Superior Medical Experts, Inc. KH works for Nested Knowledge, Inc. KMK works for and holds equity in Nested Knowledge, Inc., works for Conway Medical LLC, and holds equity in Superior Medical Experts, Inc. NH works for and holds equity in Nested Knowledge, Inc. JJH is a consultant for Medtronic and MicroVention and is a member of the scientific and medical advisory board for iSchemaView.

Background and Objectives: Diffusion basis spectrum imaging (DBSI) extracts multiple anisotropic and isotropic diffusion tensors, providing greater histopathologic specificity than diffusion tensor imaging (DTI). Persistent black holes (PBH) represent areas of severe tissue damage in multiple sclerosis (MS), and a high PBH burden is associated with worse MS disability. This study evaluated the ability of DBSI and DTI to predict which acute contrast-enhancing lesions (CELs) would persist as T 1 hypointensities (i.e. PBHs) 12 months later. We expected that a higher radial diffusivity (RD), representing demyelination, and higher DBSI-derived isotropic non-restricted fraction, representing edema and increased extracellular space, of the acute CEL would increase the likelihood of future PBH development., Methods: In this prospective cohort study, relapsing MS patients with ≥1 CEL(s) underwent monthly MRI scans for 4 to 6 months until gadolinium resolution. DBSI and DTI metrics were quantified when the CEL was most conspicuous during the monthly scans. To determine whether the CEL became a PBH, a follow-up MRI was performed at least 12 months after the final monthly scan., Results: The cohort included 20 MS participants (median age 33 years; 13 women) with 164 CELs. Of these, 59 (36 %) CELs evolved into PBHs. At Gd-max, DTI RD and AD of all CELs increased, and both metrics were significantly elevated for CELs which became PBHs, as compared to non-black holes (NBHs). DTI RD above 0.74 conferred an odds ratio (OR) of 7.76 (CI 3.77-15.98) for a CEL becoming a PBH (AUC 0.80, CI 0.73-0.87); DTI axial diffusivity (AD) above 1.22 conferred an OR of 7.32 (CI 3.38-15.86) for becoming a PBH (AUC 0.75, CI 0.66-0.83). DBSI RD and AD did not predict PBH development in a multivariable model. At Gd-max, DBSI restricted fraction decreased and DBSI non-restricted fraction increased in all CELs, and both metrics were significantly different for CELs which became PBHs, as compared to NBHs. A CEL with a DBSI non-restricted fraction above 0.45 had an OR of 4.77 (CI 2.35-9.66) for becoming a PBH (AUC 0.74, CI 0.66-0.81); a CEL with a DBSI restricted fraction below 0.07 had an OR of 9.58 (CI 4.59-20.02) for becoming a PBH (AUC 0.80, 0.72-0.87)., Conclusion: Our findings suggest that greater degree of edema/extracellular space in a CEL is a predictor of tissue destruction, as evidenced by PBH evolution., Competing Interests: Declaration of competing interest L. Wooliscroft; A. Salter; G. Adusumilli; V.A. Levasseur; P. Sun; S. Lancia; D.C. Perantie; K. Trinkaus; S.K. Song; and A.H. Cross report no disclosures relevant to the manuscript. R.T. Naismith has consulted for Abata Therapeutics, Alexion Pharmaceuticals, Biogen, Bristol Myers Squibb, Celltrion, Genentech, Genzyme, Janssen, GW Therapeutics, Horizon Therapeutics, Lundbeck, NervGen, TG Therapeutics., (Copyright © 2024. Published by Elsevier B.V.)

Background: There are an increasing number of controlled clinical trials and prospective studies, ongoing and recently completed, regarding management options for idiopathic intracranial hypertension (IIH). We present a Common Design and Data Element (CDDE) analysis of controlled and prospective IIH studies with the aim of aligning essential design and recommending data elements in future trials and enhancing data synthesis potential in IIH trials., Methods: We used PubMed and ClinicalTrials.gov to screen for ongoing and published trials assessing treatment modalities in people with IIH. After our search, we used the Nested Knowledge AutoLit platform to extract pertinent information regarding each study. We examined outputs from each study and synthesized the data elements to determine the degree of homogeneity between studies., Results: The most CDDE for inclusion criteria was the modified Dandy criteria for diagnosis of IIH, used in 9/14 studies (64%). The most CDDE for outcomes was change in visual function, reported in 12/14 studies (86%). Evaluation of surgical procedures (venous sinus stenting, cerebrospinal fluid shunt placement, and others) was more common, seen in 9/14 studies (64%) as compared with interventions with medical therapy 6/14 (43%)., Conclusions: Although all studies have similar focus to improve patient care, there was a high degree of inconsistency among studies regarding inclusion criteria, exclusion criteria, and outcomes measures. Furthermore, studies used different time frames to assess outcome data elements. This heterogeneity will make it difficult to achieve a consistent standard, and thus, making secondary analyses and meta-analyses less effective in the future. Consensus on design of trials is an unmet research need for IIH., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Background: Previous randomized controlled trials (RCTs) and meta-analyses were underpowered to demonstrate the superiority of endovascular thrombectomy (EVT) over medical therapy (MEDT) in the treatment of acute ischemic stroke due to large vessel occlusion of the posterior circulation (PC-LVO). We performed an updated systematic review and meta-analysis after the publication of the BAOCHE and ATTENTION trials to determine whether EVT can benefit patients presenting with PC-LVO., Methods: Using Nested Knowledge, we screened literature for RCTs on EVT in PC-LVO. The primary outcome was 90-day modified Rankin Scale (mRS) score 0-3, and secondary outcomes included 90-day mRS score 0-2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). A random-effects model was used to compute rate ratios (RRs) and their corresponding 95% confidence intervals (CIs)., Results: Four RCTs with 988 patients, 556 patients in the EVT arm and 432 patients in the MEDT arm, were included in the meta-analysis. EVT resulted in significantly higher rates of mRS score 0-3 (RR=1.54; 95% CI 1.16 to 2.04; P=0.002) and functional independence (RR=1.83; 95% CI 1.08 to 3.08; P=0.024), and lower rates of mortality (RR=0.76; 95% CI 0.65 to 0.90; P=0.002) at 90-day follow-up compared with MEDT alone. However, EVT patients had higher rates of sICH (RR=7.48; 95% CI 2.27 to 24.61; P<0.001)., Conclusions: EVT conferred significant patient benefit over MEDT alone in the treatment of PC-LVO. Future studies should better define patients for whom EVT is futile and determine factors that contribute to higher rates of sICH., Competing Interests: Competing interests: JJH is a consultant for Medtronic and MicroVention, a member of the medical and scientific advisory board for iSchemaView, and a member of the JNIS Editorial Board as a Member-at-Large in Neuroradiology. GWA is a consultant for Genentech and iSchemaView and holds equity in iSchemaView. DFK holds equity in Nested Knowledge, Superior Medical Editors, and Conway Medical, Marblehead Medical and Piraeus Medical; receives grant support from MicroVention, Medtronic, Balt, and Insera Therapeutics; has served on the Data Safety Monitoring Board for Vesalio; and received royalties from Medtronic. WB has compensation for consultant services from Johnson & Johnson, Stryker, Medtronic Vascular and Microvention; compensation from MIVI Neurovascular for data and safety monitoring services; stock holdings from Marblehead Medical LLC. KH works for Nested Knowledge, Inc. KMK works for, and holds equity in, Nested Knowledge, Inc., works for Conway Medical LLC, and holds equity in Superior Medical Experts, Inc. NH works for and holds equity in Nested Knowledge, Inc., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: First-pass effect (FPE) has been shown to be a predictor of favorable clinical outcomes following endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) in the anterior circulation. Literature regarding FPE for posterior circulation AIS is sparse; we conducted a systematic review and meta-analysis to explore FPE in posterior circulation stroke undergoing EVT., Materials and Methods: We conducted a systematic review of the English literature in PubMed, Embase, Scopus, and Web of Science. FPE was defined as thrombolysis in cerebral infarction (TICI) 2c-3 and modified FPE (mFPE) was defined as TICI 2b-3 in one pass. Definitions of non-FPE and non-mFPE varied among studies. The primary outcome of interest was modified Rankin Scale (mRS) 0-2. Secondary outcomes of interest were mRS 0-3, symptomatic intracranial hemorrhage (sICH), and mortality. We calculated odds ratios (OR) and corresponding 95% confidence intervals (CI). Heterogeneity was assessed with Q statistic and I 2 test., Results: Seven studies with 417 patients in the mFPE group, 942 in the non-mFPE group, 545 in the FPE group, and 1023 in the non-FPE group were included. Overall, FPE was associated with greater rates of 90-day mRS 0-2 (OR= 2.78, 95% CI= 2.11-3.65; P-value< 0.001) and mRS 0-3 (OR= 2.67, 95% CI= 1.98-3.60; P-value< 0.001); however, there was significant heterogeneity among studies for both mRS 0-2 (I 2 = 69%; P-value< 0.001) and mRS 0-3 (I 2 = 69%; P-value< 0.001). FPE and non-FPE were associated with similar rates of sICH (OR= 0.65, 95% CI= 0.40-1.07; P-value= 0.09), and no heterogeneity was observed (I 2 = 0%; P-value= 0.95). FPE was associated with lower rates of mortality (OR= 0.44, 95% CI= 0.33-0.58; P-value< 0.001), although heterogeneity was observed (I 2 = 58%; P-value= 0.01)., Conclusions: FPE is associated with favorable clinical outcomes in patients undergoing EVT for posterior circulation AIS. Future studies should work to further quantify the impact of FPE on outcomes in the posterior circulation., Competing Interests: Declaration of Competing Interest D.F.K. holds equity in Nested Knowledge, Superior Medical Editors, and Conway Medical, Marblehead Medical and Piraeus Medical. He receives grant support from MicroVention, Medtronic, Balt, and Insera Therapeutics; has served on the Data Safety Monitoring Board for Vesalio; and received royalties from Medtronic. W.B. holds equity in Nested Knowledge, Superior Medical Editors, Piraeus Medical, Sonoris Medical, and MIVI Neurovascular. He receives royalties from Medtronic and Balloon Guide Catheter Technology. He receives consulting fees from Medtronic, Stryker, Imperative Care, Microvention, MIVI Neurovascular, Cerenovus, Asahi, and Balt. He serves in a leadership or fiduciary role for MIVI Neurovascular, Marblehead Medical LLC, Interventional Neuroradiology (Editor in Chief), Piraeus Medical, and WFITN., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Collateral blood flow markers have been associated with outcomes after thrombectomy in patients presenting with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Hypoperfusion intensity ratio (HIR), a metric reflecting tissue level collaterals, is one such marker with the potential to delineate patients who do and do not do well after thrombectomy. We determined if HIR correlated with successful reperfusion after thrombectomy., Methods: Using Nested Knowledge, we screened literature for studies comparing patients with favorable versus unfavorable HIR, distinguished by a cutoff of 0.4, who underwent thrombectomy triage. The primary outcome was reperfusion success, as measured by thrombolysis in cerebral infarction ≥2b and secondary outcomes included rate of symptomatic intracranial hemorrhage, mortality at 90 days, and modified Rankin scale scores 0-2 at 90 days. A random effects model was used to compute pooled prevalence rates and their corresponding 95% confidence intervals (CI)., Results: Three studies with 973 patients, 496 with favorable HIR, and 477 with unfavorable HIR were included in this meta-analysis. The odds of reperfusion success were not significantly different between patients who had favorable versus unfavorable HIR (OR 0.96, 95% CI: 0.31-3.04) across two of the studies. Analysis of the remaining outcome variables was precluded by significant heterogeneity in data element reporting., Conclusions: This meta-analysis was considerably limited by heterogeneity. Future meta-analyses on this topic, and other topics in the field of neurointervention would benefit from improved harmonization of study design and data element reporting.

Background: Limited randomized controlled trials (RCTs) have been performed comparing endovascular thrombectomy (EVT) to medical therapy (MEDT) for acute ischemic stroke with extensive baseline ischemic injury (AIS-EBI). We conducted a systematic review and meta-analysis of RCTs reporting EVT for AIS-EBI., Methods: Using the Nested Knowledge AutoLit software, we conducted a systematic literature review from inception to 12 February 2023 within Web of Science, Embase, Scopus, and PubMed databases. Results of the TESLA trial were included on 10 June 2023. We included RCTs that compared EVT to MEDT for AIS with large ischemic core volume. The primary outcome of interest was a modified Rankin Score (mRS) 0-2. Secondary outcomes of interest included early neurological improvement (ENI), mRS 0-3, thrombolysis in cerebral infarction (TICI) 2b-3, symptomatic intracranial hemorrhage (sICH), and mortality. A random-effects model was used to calculate risk ratios (RRs) and their corresponding 95% confidence intervals (CIs)., Results: We included four RCTs with 1310 patients, 661 of whom underwent EVT and 649 of whom were treated with MEDT. EVT was associated with greater rates of mRS 0-2 (RR = 2.33, 95% CI = 1.75-3.09; P -value < 0.001), mRS 0-3 (RR = 1.68, 95% CI = 1.33-2.12; P -value < 0.001), and ENI (RR = 2.24, 95% CI = 1.55-3.24; P -value < 0.001). Rates of sICH (RR = 1.99, 95% CI = 1.07-3.69; P -value = 0.03) were greater in the EVT group. Mortality (RR = 0.98, 95% CI = 0.83-1.15; P -value = 0.79) was comparable between the EVT and MEDT groups. The rate of successful reperfusion in the EVT group was 79.9% (95% CI = 75.6-83.6)., Conclusions: Although the rate of sICH was greater in the EVT group, EVT conferred a greater clinical benefit to MEDT for AIS-EBI based on available RCTs.

Background and Purpose: Cortical venous outflow has emerged as a robust measure of collateral blood flow in acute ischemic stroke. The addition of deep venous drainage to this assessment may provide valuable information to further guide the treatment of these patients., Materials and Methods: We performed a multicenter retrospective cohort study of patients with acute ischemic stroke treated by thrombectomy between January 2013 and January 2021. The internal cerebral veins were scored on a scale of 0-2. This metric was combined with existing cortical vein opacification scores to create a comprehensive venous outflow score from 0 to 8 and stratify patients as having favorable-versus-unfavorable comprehensive venous outflow. Outcome analyses were primarily conducted using the Mann-Whitney U and χ 2 tests., Results: Six hundred seventy-eight patients met the inclusion criteria. Three hundred fifteen were stratified as having favorable comprehensive venous outflow (mean age, 73 years; range, 62-81 years; 170 men), and 363, as having unfavorable comprehensive venous outflow (mean age, 77 years; range, 67-85 years; 154 men). There were significantly higher rates of functional independence (mRS 0-2; 194/296 versus 37/352, 66% versus 11%, P  < .001) and excellent reperfusion (TICI 2c/3; 166/313 versus 142/358, 53% versus 40%, P  < .001) in patients with favorable comprehensive venous outflow. There was a significant increase in the association of mRS with the comprehensive venous outflow score compared with the cortical vein opacification score (-0.74 versus -0.67, P = .006)., Conclusions: A favorable comprehensive venous profile is strongly associated with functional independence and excellent postthrombectomy reperfusion. Future studies should focus on patients with venous outflow status that is discrepant with the eventual outcome., (© 2023 by American Journal of Neuroradiology.)

Background: Artificial intelligence (AI)-based algorithms have been developed to facilitate rapid and accurate computed tomography angiography (CTA) assessment in proximal large vessel occlusion (LVO) acute ischemic stroke, including internal carotid artery and M1 occlusions. In clinical practice, however, the detection of medium vessel occlusion (MeVO) represents an ongoing diagnostic challenge in which the added value of AI remains unclear., Purpose: To assess the diagnostic performance of AI platforms for detecting M2 occlusions., Methods: Studies that report the diagnostic performance of AI-based detection of M2 occlusions were screened, and sensitivity and specificity data were extracted using the semi-automated AutoLit software (Nested Knowledge, MN) platform. STATA (version 16 IC; Stata Corporation, College Station, Texas, USA) was used to conduct all analyses., Results: Eight studies with a low risk of bias and significant heterogeneity were included in the quantitative and qualitative synthesis. The pooled estimates of sensitivity and specificity of AI platforms for M2 occlusion detection were 64% (95% CI, 53 to 74%) and 97% (95% CI, 84 to 100%), respectively. The area under the curve (AUC) in the SROC curve was 0.79 (95% CI, 0.74 to 0.83)., Conclusion: The current performance of the AI-based algorithm makes it more suitable as an adjunctive confirmatory tool rather than as an independent one for M2 occlusions. With the rapid development of such algorithms, it is anticipated that newer generations will likely perform much better., Competing Interests: Declaration of Competing Interest KMK works for and holds equity in Nested Knowledge, Inc., works for Conway Medical LLC, and holds equity in Superior Medical Experts, Inc. JJH is a consultant for Medtronic and MicroVention and a member of the Medical and Scientific Advisory Board for iSchemaView. DFK holds equity in Nested Knowledge, Superior Medical Editors, and Conway Medical, Marblehead Medical; a consultant for MicroVention, Medtronic, Balt, and Insera Therapeutics; Data Safety Monitoring Board for Vesalio; and receiving royalties from Medtronic. AvdL received research support from Stryker, Medtronic, Penumbra and Cerenovus., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background and Objectives: Patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) in the late window (6-24 hours) can be evaluated with CT perfusion (CTP) or with noncontrast CT (NCCT) only. Whether outcomes differ depending on the type of imaging selection is unknown. We conducted a systematic review and meta-analysis comparing outcomes between CTP and NCCT for EVT selection in the late therapeutic window., Methods: This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines. A systematic literature review of the English language literature was conducted using Web of Science, Embase, Scopus, and PubMed databases. Studies focusing on late-window AIS undergoing EVT imaged through CTP and NCCT were included. Data were pooled using a random-effects model. The primary outcome of interest was rate of functional independence, defined as modified Rankin scale 0-2. The secondary outcomes of interest included rates of successful reperfusion, defined as thrombolysis in cerebral infarction 2b-3, mortality, and symptomatic intracranial hemorrhage (sICH)., Results: Five studies with 3,384 patients were included in our analysis. There were comparable rates of functional independence (odds ratio [OR] 1.03, 95% CI 0.87-1.22; p = 0.71) and sICH (OR 1.09, 95% CI 0.58-2.04; p = 0.80) between the 2 groups. Patients imaged with CTP had higher rates of successful reperfusion (OR 1.31, 95% CI 1.05-1.64; p = 0.015) and lower rates of mortality (OR 0.79, 95% CI 0.65-0.96; p = 0.017)., Discussion: Although recovery of functional independence after late-window EVT was not more common in patients selected by CTP when compared with patients selected by NCCT only, patients selected by CTP had lower mortality., (© 2023 American Academy of Neurology.)

Importance: Previous randomized clinical trials (RCTs) have supported the use of endovascular therapy (EVT) in late-window acute ischemic stroke (AIS; 6-24 hours). However, little is known about the use of EVT in very late-window AIS (>24 hours)., Objective: To examine outcomes following EVT for very late-window AIS., Data Sources: A systematic review of the English language literature was conducted using Web of Science, Embase, Scopus, and PubMed to search for articles published from database inception until December 13, 2022., Study Selection: This systematic review and meta-analysis included published studies regarding very late-window AIS treated with EVT. Multiple reviewers screened studies, and an extensive manual search of the references of included articles was performed to identify any missed articles. Of the 1754 initially retrieved studies, 7 published between 2018 and 2023 were ultimately included., Data Extraction and Synthesis: Data were extracted independently by multiple authors and evaluated for consensus. Data were pooled using a random-effects model. This study is reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guideline, and the protocol was prospectively registered with PROSPERO., Main Outcomes and Measures: The primary outcome of interest was functional independence, as assessed with 90-day modified Rankin Scale (mRS) scores (0-2). Secondary outcomes included thrombolysis in cerebral infarction (TICI) scores (2b-3 or 3), symptomatic intracranial hemorrhage (sICH), 90-day mortality, early neurological improvement (ENI), and early neurological deterioration (END). Frequencies and means were pooled with the corresponding 95% CIs., Results: This review included 7 studies involving a total of 569 patients. The mean baseline National Institutes of Health Stroke Scale score was 13.6 (95% CI, 11.9-15.5), and the mean Alberta Stroke Program Early CT Score was 7.9 (95% CI, 7.2-8.7). The mean time from last known well and/or onset to puncture was 46.2 hours (95% CI, 32.4-65.9 hours). Frequencies for the primary and secondary outcomes were 32.0% (95% CI, 24.7%-40.2%) for functional independence (90-day mRS scores of 0-2) and 81.9% (95% CI, 78.5%-84.9%) for TICI scores of 2b to 3, 45.3% (95% CI, 36.6%-54.4%) for TICI scores of 3, 6.8% (95% CI, 4.3%-10.7%) for sICH, and 27.2% (95% CI, 22.9%-31.9%) for 90-day mortality. In addition, frequencies were 36.9% (95% CI, 26.4%-48.9%) for ENI and 14.3% (95% CI, 7.1%-26.7%) for END., Conclusions and Relevance: In this review, EVT for very late-window AIS was associated with favorable frequencies of 90-day mRS scores of 0 to 2 and TICI scores of 2b to 3 and with low frequencies of 90-day mortality and sICH. These results suggest that EVT may be safe and associated with improved outcomes for very late-window AIS, although RCTs and prospective, comparative studies are needed to determine which patients may benefit from very late intervention.

Introduction: Mechanical thrombectomy (MT) is the standard of care in eligible patients presenting with acute ischemic stroke (AIS). The question of whether intravenous thrombolysis (IVT) improves outcomes in conjunction with MT remains unanswered. We performed a systematic review and meta-analysis of published randomized controlled trials (RCT) to explore outcomes of MT with and without IVT., Methods: Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, Embase, Web of science, and Scopus. Outcomes of interest included 90-day modified Rankin Scale (mRS) 0-2, thrombolysis in cerebral infarction (TICI) score 2b-3, symptomatic intracranial hemorrhage (sICH), distal embolization, and mortality. We calculated pooled risk ratios (RRs) and their corresponding 95% confidence intervals (CI)., Results: Six RCTs with 2334 patients compared outcomes of patients treated with MT alone and MT with IVT. Both treatments resulted in comparable rates of mRS 0-2 (RR = 0.96, 95% CI = 0.88-1.04; p -value = 0.282), sICH (RR = 0.80, 95% CI = 0.55-1.17; p -value = 0.253), mortality at 90-days (RR = 1.06, 95% CI = 0.88-1.28; p -value = 0.529), and distal embolization (RR = 1.10, 95% CI = 0.79-1.52; p -value = 0.572). MT alone was associated with a lower rate of TICI 2b-3 compared to MT with IVT (RR = 0.96, 95% CI = 0.93-0.99; p -value = 0.006)., Conclusions: In this meta-analysis of six RCTs, MT alone was comparable to MT plus IVT for mRS 0-2, sICH, mortality, and distal embolization; however, MT alone resulted in lower rates of TICI 2b-3. Further trials are needed to determine which patient populations benefit from MT plus IVT and to increase the power of future meta-analyses.

Background: There is limited evidence on the optimal endovascular strategy for treatment of distal medium-vessel occlusions (DMVO). The low-profile Tigertriever 13 stent-triever shows early promise as an adaptable device that can navigate the distal vasculature without increasing complication risk in DMVO., Methods: Using Nested Knowledge, we screened literature for RCTs and cohort studies on the endovascular treatment of DMVO. The primary outcome was reperfusion success, as measured by thrombolysis in cerebral infarction (TICI) ≥ 2b and secondary outcomes included rate of symptomatic intracranial hemorrhage (sICH), mortality at 90 days, and modified Rankin scale (mRS) scores 0-2 at 90 days. A random-effects model was used to compute pooled prevalence rates and their corresponding 95% confidence intervals (CI)., Results: Eleven studies with 1402 patients, 167 patients treated by Tigertriever 13 and 1235 patients treated by other devices, were included in the meta-analysis. The rate of reperfusion success was similar in patients treated by Tigertriever 13 (83.2% [95% CI: 71.5-96.7%]) versus other devices (81.6% [95% CI: 75.3-88.4%], p > 0.05). The rate of sICH was also similar in patients treated by Tigertriever 13 (7.2% [95% CI: 4.1-12.5%]) versus other devices (6.9% [95% CI: 5.5-8.8%]). There was significant heterogeneity in the reporting of mortality and mRS., Conclusions: Tigertriever 13 had similar rates of reperfusion success and sICH as other devices used for the treatment of DMVO. Heterogeneity in data element reporting prevented further analyses. Further studies evaluating Tigertriever 13 and other potential devices in DMVO should attempt to harmonize data element reporting.

To investigate whether unfavorable cerebral venous outflow (VO) predicts reperfusion hemorrhage after endovascular treatment (EVT), we conducted a retrospective multicenter cohort study of patients with acute ischemic stroke and large vessel occlusion (AIS-LVO). 629 AIS-LVO patients met inclusion criteria. VO profiles were assessed on admission CT angiography using the Cortical Vein Opacification Score (COVES). Unfavorable VO was defined as COVES ≤ 2. Reperfusion hemorrhages on follow-up imaging were subdivided into no hemorrhage (noRH), hemorrhagic infarction (HI) and parenchymal hematoma (PH). Patients with PH and HI less frequently achieved good clinical outcomes defined as 90-day modified Rankin Scale scores of ≤ 2 (PH: 13.6% vs. HI: 24.6% vs. noRH: 44.1%; p < 0.001). The occurrence of HI and PH on follow-up imaging was more likely in patients with unfavorable compared to patients with favorable VO (HI: 25.1% vs. 17.4%, p = 0.023; PH: 18.3% vs. 8.5%; p = <0.001). In multivariable regression analyses, unfavorable VO increased the likelihood of PH (aOR: 1.84; 95% CI: 1.03-3.37, p = 0.044) and HI (aOR: 2.05; 95% CI: 1.25-3.43, p = 0.005), independent of age, sex, admission National Institutes Health Stroke Scale scores and arterial collateral status. We conclude that unfavorable VO was associated with the occurrence of HI and PH, both related to worse clinical outcomes.

Background: Previous studies comparing a direct aspiration first pass technique (ADAPT) and stent retrievers have inconsistent methodologies and data reporting, limiting the ability to accurately assimilate data from different studies that would inform treatment of acute ischemic stroke (AIS) treatment., Objective: To conduct a systematic review to discuss and compare the findings of all relevant meta-analysis studies comparing the efficacy of the ADAPT and stent retriever techniques., Methods: The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), where meta-analyses comparing the efficacy of the ADAPT technique and stent retrievers in the treatment of AIS were included. We extracted all relevant data from the included studies and assessed the quality of the included meta-analyses using the Assessment of Multiple Systematic Review (AMSTAR-2)., Results: Seven relevant studies met our inclusion criteria and were suitable for the qualitative synthesis. All included studies obtained data from randomized controlled trials (RCTs) and observational investigations (including levels II, III, and IV). At the same time, none of them used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for quality assessment. In accordance with AMSTAR-2, two studies were rated 'high', while the other five were rated 'moderate'., Conclusions: Present evidence is insufficient to clarify the superiority of one modality over the other. Further RCTs on this comparison must be conducted prior to designing further meta-analyses or making conclusive interpretations. Procedure duration and cost should be taken into consideration for any future studies., Competing Interests: Competing interests: KMK works for, and holds equity in, Nested Knowledge, Inc., works for Conway Medical LLC, and holds equity in Superior Medical Experts, Inc. JJH is a consultant for Medtronic and MicroVention and a member of the Medical and Scientific Advisory Board for iSchemaView. DFK has the following conflicts: Ownership in Nested Knowledge, Inc., Superior Medical Experts, Inc., Conway Medical LLC; research support from Microvention, Balt USA, Medtronic., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Parenchymal hematoma (PH) is a major complication after endovascular treatment (EVT) for ischemic stroke. The hypoperfusion intensity ratio (HIR) represents a perfusion parameter reflecting arterial collateralization and cerebral microperfusion in ischemic brain tissue. We hypothesized that HIR correlates with the risk of PH after EVT., Methods: Retrospective multicenter cohort study of patients with large vessel occlusion who underwent EVT between 2013 and 2021 at one of the 2 comprehensive stroke centers (University Medical Center Hamburg-Eppendorf, Germany and Stanford University School of Medicine, CA). HIR was automatically calculated on computed tomography perfusion studies as the ratio of brain volume with time-to-max (Tmax) delay >10 s over volume with Tmax >6 s. Reperfusion hemorrhages were assessed according to the Heidelberg Bleeding Classification. Primary outcome was PH occurrence (PH+) or absence (PH-) on follow-up imaging. Secondary outcome was good clinical outcome defined as a 90-day modified Rankin Scale score of 0 to 2., Results: A total of 624 patients met the inclusion criteria. We observed PH in 91 (14.6%) patients after EVT. PH+ patients had higher HIR on admission compared with PH- patients (median, 0.6 versus 0.4; P <0.001). In multivariable regression, higher admission blood glucose (adjusted odds ratio [aOR], 1.08 [95% CI, 1.04-1.13]; P <0.001), extensive baseline infarct defined as Alberta Stroke Program Early CT Score ≤5 (aOR, 2.48 [1.37-4.42]; P =0.002), and higher HIR (aOR, 1.22 [1.09-1.38]; P <0.001) were independent determinants of PH after EVT. Both higher HIR (aOR, 0.83 [0.75-0.92]; P <0.001) and PH on follow-up imaging (aOR, 0.39 [0.18-0.80]; P =0.013) were independently associated with lower odds of achieving good clinical outcome., Conclusions: Poorer (higher) HIR on admission perfusion imaging was strongly associated with PH occurrence after EVT. HIR as a surrogate for cerebral microperfusion might reflect tissue vulnerability for reperfusion hemorrhages. This automated and quickly available perfusion parameter might help to assess the need for intensive medical care after EVT.

Cross study heterogeneity has limited the evidence based evaluation of middle meningeal artery embolization (MMAE) as a treatment for chronic subdural hematoma (CSDH). Ongoing trials and prospective studies suggest that heterogeneity in upcoming publications may detract from subsequent meta-analyses and systemic reviews. This study aims to describe this data heterogeneity to promote harmonization with common data elements (CDEs) in publications. ClinicalTrials.gov and PubMed were searched for published or ongoing prospective trials of MMAE. The Nested Knowledge AutoLit living review platform was utilized to classify endpoints from randomized control trials (RCTs) and prospective cohort studies comparing MMAE with other treatments. The qualitative synthesis feature was used to determine cross study overlap of outcome related data elements. Eighteen studies were included: 12 RCTs, two non-randomized controlled studies, two prospective single arm trials, one combined prospective and retrospective controlled study, and one prospective cohort study. The most commonly reported data element was recurrence (15/18), but seven heterogenous (non-comparable) definitions were used for 'recurrence'. Mortality was reported in 10/18 studies, but no common timepoint was reported in more than four studies. Re-intervention and CSDH volume were reported in eight studies, CSDH width in seven, and no other outcome was common across more than five studies. There was significant heterogeneity in data element collection even among prospective registered trials of MMAE. Even among CDEs, variation in definition and timepoints prevented harmonization. A standardized approach based on CDEs may be necessary to facilitate future meta-analyses and evidence driven evaluation of MMAE treatment of CSDH., Competing Interests: Competing interests: JJH is a consultant for Medtronic and MicroVention and is a member of the scientific and medical advisory board for iSchemaView. KMK works for and holds equity in Nested Knowledge Inc, works for Conway Medical LLC, and holds equity in Superior MedicalExperts Inc. NH works for and holds equity in Nested Knowledge Inc. ES and LS work for Nested Knowledge Inc. DFK has the following conflicts: ownership in Nested Knowledge Inc, Superior Medical Experts Inc, and Conway Medical LLC; research support from Microvention, Balt USA, and Medtronic. JF has the following conflicts: Imaging Core Lab for EMBOLISE (sponsor: Medtronic); research support from German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions- und Förderbank (IFB), Medtronic, Microvention, Route92, and Stryker; consultant for Acandis, Bayer, Boehringer Ingelheim, Cerenovus, Covidien, Medtronic, Medina, Microvention, Penumbra, Phenox, Stryker, and Transverse Medical; stock holder in Tegus Medical; deputy editor of J Neurointerv Surg. ASA is the primary investigator of the STEM Trial., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Most studies define the technical success of endovascular thrombectomy (EVT) as a Thrombolysis in Cerebral Infarction (TICI) revascularization grade of 2b or higher. However, growing evidence suggests that TICI 3 is the best angiographic predictor of improved functional outcomes. To assess the association between successful TICI revascularization grades and functional independence at 90 days, we performed a systematic review and network meta-analysis of thrombectomy studies that reported TICI scores and functional outcomes, measured by the modified Rankin Scale, using the semi-automated AutoLit software platform. Forty studies with 8691 patients were included in the quantitative synthesis. Across TICI, modified TICI (mTICI), and expanded TICI (eTICI), the highest rate of good functional outcomes was observed in patients with TICI 3 recanalization, followed by those with TICI 2c and TICI 2b recanalization, respectively. Rates of good functional outcomes were similar among patients with either TICI 2c or TICI 3 grades. On further sensitivity analysis of the eTICI scale, the rates of good functional outcomes were equivalent between eTICI 2b50 and eTICI 2b67 (OR 0.81, 95% CI 0.52 to 1.25). We conclude that near complete or complete revascularization (TICI 2c/3) is associated with higher rates of functional outcomes after EVT., Competing Interests: Competing interests: KMK works for and holds equity in Nested Knowledge Inc, works for Conway Medical LLC, and holds equity in Superior Medical Experts Inc. JJH is a consultant for Medtronic and MicroVention and a member of the Medical and Scientific Advisory Board for iSchemaView., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Mechanical thrombectomy for acute ischemic stroke (AIS) is traditionally performed via transfemoral access. While the majority of AISs are due to anterior circulation large vessel occlusions (AC-LVO), we performed a systematic review and meta-analysis to examine the feasibility of and outcomes following a transradial artery access for posterior circulation large vessel occlusion (PC-LVO) strokes. A systematic literature review of the English language literature was conducted using PubMed, MEDLINE, and Embase as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcomes of interest included 90-day modified Rankin scale (mRS) 0-2, puncture to recanalization time, and thrombolysis in cerebral infarction (TICI) scores 2b/3 and 3. We calculated pooled event rates and their corresponding 95% confidence intervals (CI) for all outcomes. We included seven studies with 68 patients in our analysis. All patients underwent mechanical thrombectomy via transradial artery access for AIS due to PC-LVO. The pooled meantime of puncture to recanalization was 29.19 (95% CI=24.05 to 35.42) minutes. Successful recanalization (TICI2b/3) was achieved in 98.69% (95% CI=93.50 to 100) of patients and complete recanalization (TICI 3) in 52.16% (95% CI=34.18 to 79.60) of the patients. Overall, 56.84% (95% CI=41.26 to 78.30) of patients achieved mRS 0-2. Transradial artery access for mechanical thrombectomy for PC-LVO stroke displays early promise and feasibility, particularly regarding very high rates of successful recanalization and low puncture to recanalization time., Competing Interests: Sources of Funding The research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number R01NS076491. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Disclosures D.F.K. holds equity in Nested Knowledge, Superior Medical Editors, Conway Medical, and Marblehead Medical; is a consultant for MicroVention, Medtronic, Balt, and Insera Therapeutics; is on the Data Safety Monitoring Board for Vesalio; receives royalties from Medtronic., (Copyright © 2022, Kobeissi et al.)

Background: Mechanical thrombectomy (MT) is now the standard-of-care treatment for acute ischemic stroke (AIS) of the anterior circulation and may be performed irrespective of intravenous tissue plasminogen activator (IV-tPA) eligibility prior to the procedure. This study aims to understand better if tPA leads to higher rates of reperfusion and improves functional outcomes in AIS patients after MT and to simultaneously evaluate the functionality and efficiency of a novel semi-automated systematic review platform. Methods: The Nested Knowledge AutoLit semi-automated systematic review platform was utilized to identify randomized control trials published between 2010 and 2021 reporting the use of mechanical thrombectomy and IV-tPA (MT+tPA) vs. MT alone for AIS treatment. The primary outcome was the rate of successful recanalization, defined as thrombolysis in cerebral infarction (TICI) scores ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS) 0-2, 90-day mortality, distal embolization to new territory, and symptomatic intracranial hemorrhage (sICH). A separate random effects model was fit for each outcome measure. Results: We subjectively found Nested Knowledge to be highly streamlined and effective at sourcing the correct literature. Four studies with 1,633 patients, 816 in the MT+tPA arm and 817 in the MT arm, were included in the meta-analysis. In each study, patient populations consisted of only tPA-eligible patients and all imaging and clinical outcomes were adjudicated by an independent and blinded core laboratory. Compared to MT alone, patients treated with MT+tPA had higher odds of eTICI ≥2b (OR = 1.34 [95% CI: 1.10; 1.63]). However, there were no statistically significant differences in the rates of 90-day mRS 0-2 (OR = 0.98 [95% CI: 0.77; 1.24]), 90-day mortality (OR = 0.94 [95% CI: 0.67; 1.32]), distal emboli (OR = 0.94 [95% CI: 0.25; 3.60]), or sICH (OR = 1.17 [95% CI: 0.80; 1.72]). Conclusions: Administering tPA prior to MT may improve the rates of recanalization compared to MT alone in tPA-eligible patients being treated for AIS, but a corresponding improvement in functional and safety outcomes was not present in this review. Further studies looking at the role of tPA before mechanical thrombectomy in different cohorts of patients could better clarify the role of tPA in the treatment protocol for AIS., Competing Interests: JP works for and holds equity in Nested Knowledge, Inc., and Superior Medical Experts, Inc. KH works for Nested Knowledge, Inc. KK works for and holds equity in Nested Knowledge, Inc., works for Conway Medical LLC, and holds equity in Superior Medical Experts, Inc. NH works for and holds equity in Nested Knowledge, Inc. JH is a consultant for Medtronic and MicroVention and is a member of the scientific and medical advisory board for iSchemaView. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Adusumilli, Pederson, Hardy, Kallmes, Hutchison, Kobeissi, Heiferman and Heit.)

The Erlenmeyer flask deformity is a common skeletal modeling deformity, but current classification systems are binary and may restrict its utility as a predictor of associated skeletal conditions. A quantifiable 3-point system of severity classification could improve its predictive potential in disease. Ratios were derived from volumes of regions of interests drawn in 50 Gaucher's disease patients. ROIs were drawn from the distal physis to 2 cm proximal, 2 cm to 4 cm, and 4 cm to 6 cm. Width was also measured at each of these boundaries. Two readers rated these 100 femurs using a 3-point scale of severity classification. Weighted kappa indicated reliability and one-way analysis of variance characterized ratio differences across the severity scale. Accuracy analyses allowed determination of clinical cutoffs for each ratio. Pearson's correlations assessed the associations of volume and width with a shape-based concavity metric of the femur. The volume ratio incorporating the metaphyseal region from 0 to 2 cm and the diametaphyseal region at 4-6 cm was most accurate at distinguishing femurs on the 3-point scale. Receiver operating characteristic curves for this ratio indicated areas of 0.95 to distinguish normal and mild femurs and 0.93 to distinguish mild and severe femurs. Volume was moderately associated with the degree of femur concavity. The proposed volume ratio method is an objective, proficient method at distinguishing severities of the Erlenmeyer flask deformity with the potential for automation. This may have application across diseases associated with the deformity and deficient osteoclast-mediated modeling of growing bone.

Gait impairments in persons with multiple sclerosis (pwMS) leading to decreased ambulation and reduced walking endurance remain poorly understood. Our objective was to assess gait asymmetry (GA) and bilateral coordination of gait (BCG), among pwMS during the six-minute walk test (6MWT), and determine their association with disease severity. We recruited 92 pwMS (age: 46.6 ± 7.9; 83% females) with a range of clinical disability, who completed the 6MWT wearing gait analysis system. GA was assessed by comparing left and right swing times, and BCG was assessed by the phase coordination index (PCI). Several functional and subjective gait assessments were performed. Results show that gait is more asymmetric and less coordinated as the disease progresses (p < 0.0001). Participants with mild MS showed significantly better BCG as reflected by lower PCI values in comparison to the other two MS severity groups (severe: p = 0.001, moderate: p = 0.02). GA and PCI also deteriorated significantly each minute during the 6MWT (p < 0.0001). GA and PCI (i.e., BCG) show weaker associations with clinical MS status than associations observed between functional and subjective gait assessments and MS status. Similar to other neurological cohorts, GA and PCI may be important parameters to assess and target in interventions among pwMS.

Objective: Multiple sclerosis (MS) lesions are heterogeneous with regard to inflammation, demyelination, axonal injury, and neuronal loss. We previously developed a diffusion basis spectrum imaging (DBSI) technique to better address MS lesion heterogeneity. We hypothesized that the profiles of multiple DBSI metrics can identify lesion-defining patterns. Here we test this hypothesis by combining a deep learning algorithm using deep neural network (DNN) with DBSI and other imaging methods., Methods: Thirty-eight MS patients were scanned with diffusion-weighted imaging, magnetization transfer imaging, and standard conventional MRI sequences (cMRI). A total of 499 regions of interest were identified on standard MRI and labeled as persistent black holes (PBH), persistent gray holes (PGH), acute black holes (ABH), acute gray holes (AGH), nonblack or gray holes (NBH), and normal appearing white matter (NAWM). DBSI, diffusion tensor imaging (DTI), and magnetization transfer ratio (MTR) were applied to the 43,261 imaging voxels extracted from these ROIs. The optimized DNN with 10 fully connected hidden layers was trained using the imaging metrics of the lesion subtypes and NAWM., Results: Concordance, sensitivity, specificity, and accuracy were determined for the different imaging methods. DBSI-DNN derived lesion classification achieved 93.4% overall concordance with predetermined lesion types, compared with 80.2% for DTI-DNN model, 78.3% for MTR-DNN model, and 74.2% for cMRI-DNN model. DBSI-DNN also produced the highest specificity, sensitivity, and accuracy., Conclusions: DBSI-DNN improves the classification of different MS lesion subtypes, which could aid clinical decision making. The efficacy and efficiency of DBSI-DNN shows great promise for clinical applications in automatic MS lesion detection and classification., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: We aimed to determine the rate of herbal medicine usage and the treatment-seeking patterns of children aged ≤5 y with presumed or confirmed malaria in an endemic area of Uganda., Methods: We interviewed guardians of 722 children aged 6 months to 5 y, who had experienced an episode of presumed malaria in the previous 3 months, about the illness history., Results: Overall, 36.1% of patients took herbal medicines but most also sought modern medical care; 79.2% received Artemether-Lumefantrine (AL), but only 42.7% received the correct AL dose. Of the 36.6% of patients treated in drug shops, 9.8% had a diagnostic test and 30.2% received the correct dose of AL. Antibiotics were frequently provided with AL at drug shops (62%) and formal health centers (45%). There were no significant differences in the self-reported outcomes associated with different treatments., Conclusion: Almost all of the patients who took herbal medicine also took modern antimalarials, so further research is needed to explore potential interactions between them. Although formal health facilities provided the correct diagnosis and dose of AL to a majority of children with malaria, many children still received inappropriate antibiotics. Quality of care was worse in drug shops than in formal health facilities., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To investigate the current prevalence and management of dyspepsia in rural Eastern Uganda., Methods: Residents older than 18 years of age across 95 study sites in Namutumba District, Eastern Uganda were surveyed. Each respondent was administered a questionnaire about dyspepsia and pertinent health-seeking behaviors. Health workers at 12 different clinics were also assessed on their competence in managing dyspepsia. Proportion-based analysis was used to determine self-reported outcome variables reported in this study, including: prevalence of dyspepsia; breakdown of symptoms; initial diagnosis location; management strategies; and appropriate medication usage., Results: 397 residents (average age of 41.2 years) participated in this study (54.4% males, 45.6% females). 57.9% self-reported currently having dyspepsia, of average duration 4.5 years. Of this subset, 87% reported experiencing epigastric pain, and 42.2% believed that ulcers were "wounds in the stomach." Only 3% of respondents had heard of Helicobacter pylori (Hp) . Respondents varied in their management of dyspepsia, with frequent eating (39.1%), doing nothing (23.9%), and taking Western medicine (20%) being the most common strategies. The diagnosis of "peptic ulcer disease" was made by a health worker in 64.3% of cases, and 27% of cases were self-diagnosed. Notably, 70.3% of diagnoses at formal health centers were based on clinical symptoms alone and only 22.7% of respondents received treatment according to Ugandan Ministry of Health guidelines. Among the 12 health care workers surveyed, 10 cited epigastric pain as a common symptom of "ulcer," although only two reported having heard of Hp. Only two out of 12 clinics had the capability to prescribe the triple therapy as treatment for presumed Hp., Conclusion: There is a high incidence of dyspepsia in Eastern Uganda, and current management strategies are poor and inconsistent, and may contribute to antibiotic resistance. Further studies are needed to investigate the causes of dyspepsia to guide appropriate management.

The standard functional tool for gait assessment in multiple sclerosis (MS) clinical trials has been the 25-Foot Timed Walk Test, a measure of gait speed. Straight-line gait assessment may not reflect adequately upon balance and coordination. Walking tests with turns may add additional information towards understanding gait and balance status, and be more reflective of ambulation in the community. Understanding the impact of turn parameters on patient-reported outcomes of balance and walking would help MS clinicians better formulate treatment plans for persons with gait limitations. In this study, ninety-one persons with MS (Expanded Disability Status Score; EDSS, range: 0-6.5) were enrolled in an initial cross-sectional study. Twenty-four subjects (EDSS, range:1.0-6.0) completed a follow-up visit an average of 12 months later. Spatiotemporal gait analysis was collected at both visits using APDM Opal wireless body-worn sensors while performing the Timed-Up-and-Go (TUG) and 6-Minute Walk Test (6MWT). For both cross-sectional and longitudinal data, regression analyses determined the impact on the addition of turning parameters to stride velocity (SV), in the prediction of self-reported balance confidence (Activities-Specific Balance Confidence Scale (ABC)) and walking limitation (12-item Multiple Sclerosis Walking Scale (MSWS-12)). The addition of 6MWT peak turn velocity (PTV) to 6MWT SV increased the predictive power of the 6MWT for the ABC from 20% to 33%, and increased the predictive power from 28% to 41% for the MSWS-12. TUG PTV added to TUG SV also strengthened the relationship of the TUG for the ABC from 19% to 28%, and 27% to 36% for the MSWS-12. For those with 1 year follow-up, percent change in turn number of steps (TNS%Δ) during the 6MWT added to 6MWT SV%Δ improved the modeling of ABC%Δ from 24% to 33%. 6MWT PTV%Δ added to 6MWT SV%Δ increased the predictive power of MSWS-12%Δ from 8% to 27%. Conclusively, turn parameters improved modeling of self-perceived balance confidence and walking limitations when added to the commonly utilized measure of gait speed. Tests of longer durations with multiple turns, as opposed to shorter durations with a single turn, modeled longitudinal change more accurately. Turn speed and stability should be qualitatively assessed during the clinic visit, and use of multi-faceted tests such as the TUG or 6MWT may be required to fully understand gait deterioration in persons with MS., Competing Interests: The following are the competing interests: Joanne Wagner (Acorda Therapeutics – stock; Greenwich Biosciences – salary, stock) and Robert Naismith (Consultant for Acorda, Alkermes, Biogen, EMD Serono, Genentech, Genzyme, Novartis, Teva). The funder did not provide support in the form of salaries for authors, and did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Background: Improved imaging methods are critical to assess neurodegeneration and remyelination in multiple sclerosis. Chronic hypointensities observed on T1-weighted brain MRI, "persistent black holes," reflect severe focal tissue damage. Present measures consist of determining persistent black holes numbers and volumes, but do not quantitate severity of individual lesions., Objective: Develop a method to differentiate black and gray holes and estimate the severity of individual multiple sclerosis lesions using standard magnetic resonance imaging., Methods: 38 multiple sclerosis patients contributed images. Intensities of lesions on T1-weighted scans were assessed relative to cerebrospinal fluid intensity using commercial software. Magnetization transfer imaging, diffusion tensor imaging and clinical testing were performed to assess associations with T1w intensity-based measures., Results: Intensity-based assessments of T1w hypointensities were reproducible and achieved > 90% concordance with expert rater determinations of "black" and "gray" holes. Intensity ratio values correlated with magnetization transfer ratios (R = 0.473) and diffusion tensor imaging metrics (R values ranging from 0.283 to -0.531) that have been associated with demyelination and axon loss. Intensity ratio values incorporated into T1w hypointensity volumes correlated with clinical measures of cognition., Conclusions: This method of determining the degree of hypointensity within multiple sclerosis lesions can add information to conventional imaging., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Performance tests are important to characterize patient disabilities and functional changes. The Osteoarthritis Research Society International and others recommend the 30-second Chair Stand Test and Stair Climb Test, among others, as core tests that capture two distinct types of disability during activities of daily living. However, these two tests are limited by current protocols of testing in clinics. There is a need for an alternative that allows remote testing of functional capabilities during these tests in the osteoarthritis patient population., Objective: Objectives are to (1) develop an app for testing the functionality of an iPhone's accelerometer and gravity sensor and (2) conduct a pilot study objectively evaluating the criterion validity and test-retest reliability of outcome variables obtained from these sensors during the 30-second Chair Stand Test and Stair Climb Test., Methods: An iOS app was developed with data collection capabilities from the built-in iPhone accelerometer and gravity sensor tools and linked to Google Firebase. A total of 24 subjects performed the 30-second Chair Stand Test with an iPhone accelerometer collecting data and an external rater manually counting sit-to-stand repetitions. A total of 21 subjects performed the Stair Climb Test with an iPhone gravity sensor turned on and an external rater timing the duration of the test on a stopwatch. App data from Firebase were converted into graphical data and exported into MATLAB for data filtering. Multiple iterations of a data processing algorithm were used to increase robustness and accuracy. MATLAB-generated outcome variables were compared to the manually determined outcome variables of each test. Pearson's correlation coefficients (PCCs), Bland-Altman plots, intraclass correlation coefficients (ICCs), standard errors of measurement, and repeatability coefficients were generated to evaluate criterion validity, agreement, and test-retest reliability of iPhone sensor data against gold-standard manual measurements., Results: App accelerometer data during the 30-second Chair Stand Test (PCC=.890) and gravity sensor data during the Stair Climb Test (PCC=.865) were highly correlated to gold-standard manual measurements. Greater than 95% of values on Bland-Altman plots comparing the manual data to the app data fell within the 95% limits of agreement. Strong intraclass correlation was found for trials of the 30-second Chair Stand Test (ICC=.968) and Stair Climb Test (ICC=.902). Standard errors of measurement for both tests were found to be within acceptable thresholds for MATLAB. Repeatability coefficients for the 30-second Chair Stand Test and Stair Climb Test were 0.629 and 1.20, respectively., Conclusions: App-based performance testing of the 30-second Chair Stand Test and Stair Climb Test is valid and reliable, suggesting its applicability to future, larger-scale studies in the osteoarthritis patient population., (©Gautam Adusumilli, Solomon Eben Joseph, Michael A Samaan, Brooke Schultz, Tijana Popovic, Richard B Souza, Sharmila Majumdar. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 27.10.2017.)

Background: Skeletal maturation is an integral part of individual pattern of growth and development and is a continuous process. Peak growth velocity in standing height is the most valid representation of the rate of overall skeletal growth. Ossification changes of hand wrist and cervical vertebrae are the reliable indicators of growth status of individual. The objective of this study was to compare skeletal maturation as measured by hand wrist bone analysis and cervical vertebral analysis., Materials and Methods: Hand wrist radiographs and lateral cephalograms of 72 subjects aged between 7 and 16 years both male and female from the patients visiting Department of Orthodontics and Dentofacial Orthopedics, R.V. Dental College and Hospital. The 9 stages were reduced to 5 stages to compare with cervical vertebral maturation stage by Baccetti et al. The Bjork, Grave and Brown stages were reduced to six intervals to compare with cervical vertebral maturational index (CVMI) staging by Hassel and Farman. These measurements were then compared with the hand wrist bone analysis, and the results were statistically analyzed using the Mann-Whitney test., Results: There was no significant difference between the hand wrist analysis and the two different cervical vertebral analyses for assessing skeletal maturation. There was no significant difference between the two cervical vertebral analyses, but the CVMI method, which is visual method is less time consuming., Conclusion: Vertebral analysis on a lateral cephalogram is as valid as the hand wrist bone analysis with the advantage of reducing the radiation exposure of growing subjects.

Introduction: Non-syndromic tooth agenesis is a congenital anomaly with significant medical, psychological, and social ramifications. There is sufficient evidence to hypothesize that locus for this condition can be identified by candidate genes., Aim of the Study: The aim of this study was to test whether MSX1 671 T > C gene variant was involved in etiology of non-syndromic tooth agenesis in Raichur patients., Materials and Methods: Blood samples were collected with informed consent from 50 subjects having non-syndromic tooth agenesis and 50 controls. Genomic deoxyribonucleic acid (DNA) was extracted from the blood samples, polymerase chain reaction (PCR) was performed, and restriction fragment length polymorphism (RFLP) was performed for digestion products that were evaluated., Results: The results showed positive correlation between MSX1671 T > C gene variant and non-syndromic tooth agenesis in Raichur patients., Conclusion: MSX1 671 T > C gene variant may be a good screening marker for non-syndromic tooth agenesis in Raichur patients.

Background: Non Syndromic tooth agenesis is a congenital anomaly with significant medical, psychological and social ramifications. There is sufficient evidence to hypothesize that locus for this condition can be identified by candidate genes. The aim of this study was to test whether MSX1 671 T>C gene variant was involved in etiology of Non Syndromic tooth agenesis in Raichur Patients., Materials & Methods: Blood samples were collected with informed consent from 50 subjects having Non Syndromic tooth agenesis and 50 controls. Genomic DNA was extracted from the blood samples, Polymerase Chain Reaction was performed (PCR) and Restriction Fragment Length Polymorphism (RFLP) was performed for digestion products that were evaluated., Results: The RESULTS showed positive correlation between MSX1671 T>C gene variant and Non Syndromic tooth agenesis in Raichur Patients., Conclusion: MSX1 671 T>C gene variant may be a good screening marker for Non Syndromic tooth agenesis in Raichur Patients . How to cite this article:Reddy NA, Adusumilli G, Devanna R, Pichai S, Rohra MG, Arjunan S. Msx1 Gene Variant - Its Presence in Tooth Absence - A Case Control Genetic Study. J Int Oral Health 2013; 5(5):20-6.

Aim: The aim is to compare and evaluate the airway dimension changes, adenoidal nasopharyngeal ratio (ANR), airway area and airway percentage in patients in pre- and postadenoidectomy with normal individuals., Materials and Methods: After obtaining informed consent, a sample of 15 patients (eight males and seven females) of 7 to 12 years were selected for adenoidectomy by an otolaryngologist, lateral cephalograms were taken in natural head position before adenoidectomy and after 1 month postadenoidectomy. Statastical analysis was done to evaluate the results using Statastical Package for Social Sciences. Results showed airway (P1, P2, P3, P4), airway percentage, airway area showed significant increase (p < 0.0001), whereas ANR showed significant reduction after 1 month postadenoidectomy., Conclusion: One month postadenoidectomy showed increased airway area, airway percentage and reduced ANR., Clinical Significance: Obstructive mouth breathing due to adenoids in growing children can cause alteration in craniofacial morphology leading to adenoid facies, adenoidectomy procedure helps in alleviating the obstruction and facilitates the normal growth of craniofacial complex.