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Ami B Patel, Joohi Jimenez-Shahed Department of Neurology, Baylor College of Medicine, Houston, TX, USA Abstract: Inhaled levodopa is a newly emerging therapeutic option in the treatment of “off” symptoms associated with Parkinson’s disease (PD). Its mode of delivery offers more rapid absorption of levodopa and shorter onset of clinical benefit compared to oral formulations, and has been shown to be feasible for use in patients with PD experiencing worse motor function due to declining plasma levodopa levels. Clinical development of this compound is supported by preclinical, Phase I–III, long-term-safety studies and studies in special populations, including otherwise-healthy asthmatics and smokers. These investigations demonstrated that the drug is well tolerated without risk of long-term (up to 1 year) changes in pulmonary function or spirometry measures. The most common side effects among PD patients were a mild cough, upper respiratory tract infection, nausea, sputum discoloration, and dyskinesia. Inhaled levodopa offers a different administration method and side-effect profile from the currently available options for rescue therapy for Off periods in PD, though comparative studies have not been performed. The drug is presently under review by the US Food and Drug Administration. Keywords: levodopa, dry-powder inhalation, motor fluctuations, dyskinesia, spirometry

Joanna Ismail, Anmol Bipin PatelDepartment of Undergraduate Medicine, Faculty of Medicine, Imperial College London, London, UKThe situational judgment test (SJT) is an assessment used by the UK Foundation Programme (UKFP) in stratifying medical students applying for their first clinical jobs. It aims to measure domains including problem solving, working in a team, communication skills, working under pressure, commitment and professionalism.1,2 Question stems are based on situations observed in clinical practice, whereby examinees rank the appropriateness of various responses offered. Controversy in student and expert opinion makes the SJT a highly debated topic in medical education.

Anmol Bipin Patel, Harkaran Singh Kalkat Department of Undergraduate Medicine, Faculty of Medicine, Imperial College London, London, UK Students are exposed to a range of teaching methods during the pre-clinical and clinical years of medical school. At Imperial College London, the pre-clinical years involve a predominantly lecture-based approach, with the aim of efficiently disseminating large volumes of knowledge to a large cohort. As clinical years approach, there is a swift move towards hospital-based teaching, where students have the independence to make the most of learning opportunities during placements. As learning objectives during medical studies, a corresponding change in teaching method is necessary. However, a sudden transition between teaching models or an overreliance on any one can be detrimental.

Anmol Bipin Patel, Harkaran Singh KalkatDepartment of Undergraduate Medicine, Faculty of Medicine, Imperial College London, London, UKThe clinical years of medical school place a large importance on “bedside teaching”. Students, often in front of their peers, are expected to demonstrate their knowledge and are pushed until gaps in that knowledge are bridged. However, the environment in which these sessions take place may not always be conducive to effective learning. Teaching by intimidation, also known as “pimping”, has long had a place in traditional medical education and is perpetuated by each generation of doctors teaching in the manner that they were taught. Students describe this as an intimidating questioning style overridden by a hostile attitude aimed at belittling the learner whilst reinforcing a dominant hierarchy.1,2 Although its persistence may be evidence of its inherent success, the approach certainly has as its detractions.

The authors report a novel application of cement augmentation for treatment of a symptomatic sternal fracture. Sternal fractures often cause debilitating pain and can affect ventilation. Given the success of vertebroplasty in patients in treating back pain, the authors used a similar technique in a 56-year-old woman with chronic obstructive pulmonary disease and an acute comminuted sternal fracture refractory to conservative management. The authors used computed tomography guidance and cement augmentation for the fracture. The patient subsequently reported good pain relief and improved breathing. Sternoplasty may be a viable alternative for patients with sternal fractures and refractory pain. [ABSTRACT FROM AUTHOR]

Objective: To identify specific domains and traits that are most affected in patients with sickle cell anemia and traits with respect to normal children.Methods: Children attending the regional hemoglobinopathy center at IGMC, Nagpur in age group of 8-14 years were assessed. Of 52 children studied, 25 had sickle cell anemia (SCA), 12 had sickle cell trait (SCT) and 15 wre normal control. The (quality of life (QOL) was assessed using multidimensional interview based questionnaire.Results: All domains, physical, psychosocial, cognitive and morbidity were affected. In SCA playing and mobility were most affected. There was feeling of sadness or disinterest and lack of support from teachers. The school attendance, vocational achievement perception, entertainment and participation in cultural activities were also affected. The intensity of weakness and pain was greater in SCA children who left that they were affected by a major illness. The unusual finding was that the SCT children also showed affection of all domains as compared to normal children, which was perhaps due to the stigma of the disease.Conclusion: QOL is affected in children with sickle cell disease (SCD) and to a lesser extent in SCT. Interventions to improve QOL should target the affected items. Improving awareness of the disease and its manifestation will help to alleviate the psychosocial affliction of children with SCT. [ABSTRACT FROM AUTHOR]

Aim. To report the management and orthograde technique of MTA placement in case of reverse architecture maxillary premolars. Summary. Two cases of 17-year-old and 21-year-old female patients were referred to endodontic speciality for management of maxillary premolar having reverse architecture with wide immature open apex like a bell mouth. In both the cases, after control of intraradicular infection, it was decided to use MTA for apexification and obturation of canals. Orthograde placement of MTA is a challenging procedure in terms of length control and condensation especially in divergent irregular reverse architecture wide open apex. A novel technique with the help of finger plugger, sterilized paper point, and ultrasonic agitation for 3D compaction of MTA at apical reverse architecture was used. Thickening of the canal wall and complete apical closure were confirmed one year after the treatment.

Currently, cancer is a serious health challenge with predominance beyond restrictions. Breast cancer remains one of the major contributors to cancer-related morbidity and mortality in women. Chemotherapy continues to be crucial in the treatment of all variants of cancer. Several antitumor drugs are presently in different phases of clinical trials, whereas many more have been approved for clinical use. However, these drugs have the potential to cause adverse effects, and certain individuals may become resistant to them, which would eventually reduce the drug's efficacy. Therefore, it is essential to discover, develop, and improve newer anticancer drug molecules that could potentially inhibit proliferative pathways. In recent years, quinazolinone derivatives, more specifically halogen-substituted 4(3H)-quinazolinone, have drawn attention as a promising new class of chemotherapeutic agents. In addition, these molecules showed significant inhibition in micromolar ranges when tested in vitro against the MCF-7 cell line. Therefore, this study aims to emphasize the intriguing versatility of halogen atoms, providing an in-depth summary and highlighting recent developments in the anticancer properties of halogenated 4(3H)-quinazolinones. It also features a detailed discussion of the structure-activity relationship (SAR) of various functional groups and their interaction with amino acid residues utilizing molecular docking studies. The intent is to foster novel discoveries that can inspire innovative investigations in this domain. Hence, this study simplifies the drug design and development strategies by prolonging the array of pharmacologically active candidates., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Objective: The objective of our study was to determine the prevalence of anemia among 14-19 years school going girls, risk factors for it and profile of micronutrient status among rural girls from western state of India., Design: Using a cross-sectional design, we obtained information on socio-demography, menstruation, dietary habits, knowledge and daily consumption of the government recommended iron and folic acid (IFA) tablets, and anthropometry. Blood was collected to assess haemoglobin, red blood cell indices, serum iron, folate and vitamin B 12 levels., Settings: Nagpur district, Maharashtra, India., Participants: A total of 221 girls aged 14-19 years studying in 24 government institutes included., Results: 57% girls were anaemic, 84% had deficiency of one or more micronutrients and 60% were malnourished based on Body Mass Index (BMI). The prevalence of iron, vitamin B 12 and folate deficiency was 37.7%, 69.8% and 1.4% respectively. Among anaemic girls, iron and vitamin B 12 deficiency was observed in 45.5% and 67.5% respectively, vs. among non-anaemic girls it was 27% and 73% respectively. Iron deficiency was a predictor of anaemia and its severity. Girls residing in non-nuclear family were more likely to have anaemia. The consumption of daily non-vegetarian food and green leafy vegetables was 3% and 3.6% respectively. Only 9% consumed IFA tablets in the past two weeks., Conclusions: Anemia is common in adolescent girls, particularly associated with iron and vitamin B12 deficiency. There is need to reconsider the approach to prevention of anaemia in adolescent girls, particularly before they become pregnant.

Psoriasis is a chronic, inflammatory skin disease that affects over 60 million adults and children globally. It is classically characterized by pink plaques covered with silver scales on the extensor surfaces, trunk, or scalp. In this report, we describe the case of a woman in her late 60s with psoriasis presenting as a painful plaque on her left breast. This case highlights the importance of considering psoriasis as a differential diagnosis in patients with unilateral breast plaques, even in the absence of typical psoriasis scaling elsewhere on the body., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background and Aim: The clinical importance and management of vasospasm as a complication during endovascular stroke treatment (EVT) has not been well studied. We sought to investigate current expert opinions in neurointervention and therapeutic strategies of iatrogenic vasospasm during EVT., Methods: We conducted an anonymous international online survey (4 April 2023 to 15 May 2023) addressing treatment standards of neurointerventionalists (NIs) practising EVT. Several illustrative cases of patients with vasospasm during EVT were shown. Two study groups were compared according to the NI's opinion regarding the potential influence of vasospasm on patient outcome after EVT using descriptive analysis., Results: In total, 534 NI from 56 countries responded, of whom 51.5% had performed >200 EVT. Vasospasm was considered a complication potentially influencing the patient's outcome by 52.6% (group 1) whereas 47.4% did not (group 2). Physicians in group 1 more often added vasodilators to their catheter flushes during EVT routinely (43.7% vs 33.9%, p=0.033) and more often treated severe large-vessel vasospasm with vasodilators (75.3% vs 55.9%; p<0.001), as well as extracranial vasospasm (61.4% vs 36.5%, p<0.001) and intracranial medium-vessel vasospasm (27.1% vs 11.2%, p<0.001), compared with group 2. In case of a large-vessel vasospasm and residual and amenable medium-vessel occlusion during EVT, the study groups showed different treatment strategies. Group 2 continued the EVT immediately more often, without initiating therapy to treat the vasospasm first (9.6% vs 21.1%, p<0.001)., Conclusion: There is disagreement among NIs about the clinical relevance of vasospasm during EVT and its management. There was a higher likelihood of use of preventive and active vasodilator treatment in the group that perceived vasospasm as a relevant complication as well as differing interventional strategies for continuing an EVT in the presence of a large-vessel vasospasm., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The Woven EndoBridge (WEB) device is emerging as a novel therapy for intracranial aneurysms, but its use for off-label indications requires further study. Using machine learning, we aimed to develop predictive models for complete occlusion after off-label WEB treatment and to identify factors associated with occlusion outcomes., Methods: This multicenter, retrospective study included 162 patients who underwent off-label WEB treatment for intracranial aneurysms. Baseline, morphological, and procedural variables were utilized to develop machine-learning models predicting complete occlusion. Model interpretation was performed to determine significant predictors. Ordinal regression was also performed with occlusion status as an ordinal outcome from better (Raymond Roy Occlusion Classification [RROC] grade 1) to worse (RROC grade 3) status. Odds ratios (OR) with 95 % confidence intervals (CI) were reported., Results: The best performing model achieved an AUROC of 0.8 for predicting complete occlusion. Larger neck diameter and daughter sac were significant independent predictors of incomplete occlusion. On multivariable ordinal regression, higher RROC grades (OR 1.86, 95 % CI 1.25-2.82), larger neck diameter (OR 1.69, 95 % CI 1.09-2.65), and presence of daughter sacs (OR 2.26, 95 % CI 0.99-5.15) were associated with worse aneurysm occlusion after WEB treatment, independent of other factors., Conclusion: This study found that larger neck diameter and daughter sacs were associated with worse occlusion after WEB therapy for aneurysms. The machine learning approach identified anatomical factors related to occlusion outcomes that may help guide patient selection and monitoring with this technology. Further validation is needed., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

There has been remarkable progress in the development of novel therapeutic approaches for patients with polycythemia vera (PV). Historically, therapy goals in PV were to mitigate thrombotic risks and control blood counts and symptoms. There is now increased focus on disease modification through progressive attrition of JAK2 -mutant stem/progenitor cells. The approval of ropeginterferon, a novel monoPEGylated interferon, coupled with findings from LOW-PV and longer-term data from CONTINUATION-PV that strongly support a disease-modifying effect for interferon therapy, have transformed the treatment paradigm for this disorder. Results from MAJIC-PV demonstrate that disease modification can also be induced with JAK inhibitors, suggesting an urgent need to incorporate prospective molecular monitoring into PV trials. Novel agents, such as hepcidin mimetics, aim to help patients with PV restore normal hematocrit levels and become phlebotomy-free. In this review, we will summarize past, current and future approaches to PV management and highlight findings from key clinical studies.

Background and Objectives: Moyamoya disease (MMD) is characterized by progressive steno-occlusion of the internal carotid arteries, leading to compensatory collateral vessel formation. The optimal surgical approach for MMD remains debated, with bilateral revascularization potentially offering more comprehensive protection but involving more extensive surgery compared to unilateral revascularization. This study aims to compare bilateral revascularization and unilateral revascularization short-term safety profile in the treatment of MMD., Methods: This multicenter retrospective study included patients with MMD who underwent surgical revascularization at 13 academic institutions. Patients were categorized into unilateral and bilateral revascularization groups. Data collected included demographics, clinical characteristics, and outcomes. Propensity score matching was used to balance baseline characteristics. Statistical analyses were conducted using Stata (V.17.0; StataCorp)., Results: A total of 497 patients were included, including 90 who had bilateral revascularization and 407 who had unilateral revascularization. Bilateral revascularization was associated with more perioperative asymptomatic strokes (10% vs 2.4%; odds ratio [OR] 4.41, 95% CI 1.73 to 11.19, P = .002) and higher rates of excellent functional outcomes (modified Rankin Scale 0-1) at discharge (92.2% vs 79.1%; OR 3.12, 95% CI 1.39 to 7, P = .006). After propensity score matching, 57 matched pairs were analyzed. There was a higher rate, though not statistically significant difference, of perioperative stroke in the bilateral revascularization group (15.7% vs 8.7%; OR 1.95, 95% CI 0.61 to 6.22, P = .26). No significant differences were noted in modified Rankin scale 0 to 1 and 0 to 2 scores at discharge, National Institute of Health Stroke Scale at discharge, intraoperative complications, or length of hospital stay. The follow-up stroke rates were also not significantly different (OR 0.40, 95% CI 0.11 to 1.39, P = .15)., Conclusion: This study found no significant differences between bilateral and unilateral revascularization in MMD. Patients who had bilateral revascularization had higher tendency of perioperative stroke, though not statistically significant. Further prospective studies are needed to validate these results., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: There is a need for unified guidance in the management of acneiform rash induced by epidermal growth factor receptor inhibitors (EGFRi) among dermatologists., Objective: To establish unified international guidelines for the management of acneiform rash caused by EGFR inhibitors, based on an experts' Delphi consensus., Methods: The initiative was led by five members of the European Academy of Dermatology and Venereology Task Force 'Dermatology for Cancer Patients' who developed a questionnaire that was circulated to a group of 32 supportive oncodermatology experts in Europe, Canada, Argentina, the US States and Asia. The questionnaire consisted of 84 statements in total, regarding diagnosis and treatment of EGFRi-induced acneiform rash. Experts responded to an anonymous 5-point Likert scale survey. The coordinators collected the first-round responses that were checked for consensus (≥75% agreement in positive [agree or strongly agree] or in negative [disagree or strongly disagree] vote). The statements that did not reach strong consensus in the first round were revised, according to experts' feedback, for a second-round survey., Results: Strong consensus was reached in 75/84 (89.3%) of the statements, whilst moderate consensus was achieved in 6/84 elements. Key points include consideration of low-dose isotretinoin for refractory grade II/III acneiform rash, use of topical steroid-sparing agents like topical pimecrolimus in the maintenance phase and use of doxycycline in either 100 or 200 mg per day as prophylactic treatment. Interestingly, experts did not recommend topical antibiotics, neither for prevention, nor for treatment. Consensus failure in 3/84 objects is mostly related to the lack of robust data on these topics., Conclusion: This consensus offers crucial insights often overlooked by radiotherapists, general practitioners, dermatologists and oncologists, and it is expected to improve the management of oncologic patients treated with EGFRi in different settings and continents., (© 2024 European Academy of Dermatology and Venereology.)

Objective: Behaviour Change Communication (BCC) intervention programmes often lack documentation of successful processes. This manuscript aims to describe the development of Program Impact Pathway (PIP) using Theory of Change (ToC) approach for a mHealth BCC intervention titled 'Mobile Solutions Aiding Knowledge for Health Improvement (M-SAKHI)' aimed at reducing stunting in infants at 18 months of age., Design: The PIP was developed using ToC to design the intervention and plan its implementation. Literature review and data from previous pilots helped to identify health service gaps that needed to be addressed by the PIP of this intervention., Setting: M-SAKHI was implemented in 244 villages under governance of forty primary health centres of Nagpur and Bhandara districts of eastern Maharashtra in central India., Participants: The study investigators and the public health stakeholders participated in developing the PIP. M-SAKHI evaluation study recruited 2501 pregnant women who were followed up through delivery until their infants were 18 months old., Results: The PIP was developed, and it identified the following pathways for the final impact: (1) improving maternal and infant nutrition, (2) early recognition of maternal and infant danger signs, (3) improving access and utilisation to healthcare services, (4) improving hygiene, sanitation and immunisation practices, and (5) improving implementation and service delivery of community health workers through their training, monitoring and supervision in real time., Conclusion: This paper will illustrate the significance of development of PIP for M-SAKHI. It can aid other community-based programmes to design their PIP for nutrition-based BCC interventions.

Background: Despite the proven effectiveness of endovascular therapy (EVT) in acute ischemic strokes (AIS) involving anterior circulation large vessel occlusions, isolated posterior cerebral artery (PCA) occlusions (iPCAo) remain underexplored in clinical trials. This study investigates the comparative effectiveness and safety of EVT against medical management (MM) in patients with iPCAo., Methods: This multinational, multicenter propensity score-weighted study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. We included iPCAo patients treated with either EVT or MM. The primary outcome was the modified Rankin Scale (mRS) at 90 days, with secondary outcomes including functional independence, mortality, and safety profiles such as hemorrhagic complications., Results: A total of 177 patients were analyzed (88 MM and 89 EVT). EVT showed a statistically significant improvement in 90-day mRS scores (OR = 0.55, 95% CI = 0.30-1.00, p  = 0.048), functional independence (OR = 2.52, 95% CI = 1.02-6.20, p  = 0.045), and a reduction in 90-day mortality (OR = 0.12, 95% CI = 0.03-0.54, p  = 0.006) compared to MM. Hemorrhagic complications were not significantly different between the groups., Conclusion: EVT for iPCAo is associated with better neurological outcomes and lower mortality compared to MM, without an increased risk of hemorrhagic complications. Nevertheless, these results should be interpreted with caution due to the study's observational design. The findings are hypothesis-generating and highlight the need for future randomized controlled trials to confirm these observations and establish definitive treatment guidelines for this patient population., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Dr. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading), and Artedrone (Board); all not directly related to the present work. Dr. Henninger received support from W81XWH-19-PRARP-RPA form the CDMRP/DoD, NS131756 and U24NS113844 from the NINDS, and NR020231 from the NINR and received compensation from Myrobalan, Inc. and General Dynamics during the conduct of this study unrelated to this work. Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro, and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson, and Phenox (paid lectures), all not directly related to the present work. Dr. Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc, and Arsenal Medical, he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular, and Stryker Neurovascular, and holds stocks in InNeuroCo, Agile, Perfuze, Galaxy, and NTI. Dr. Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally). Dr. Jabbour is a consultant for Medtronic, Microvention, and Cerus.

Objective: The Woven EndoBridge (WEB) device was approved to treat wide-necked bifurcation aneurysms. The device is designed as an intrasaccular flow disruptor covering aneurysm widths up to 10 mm. Although prior studies combined all aneurysm sizes, it is known that aneurysms behave differently in response to endovascular treatment based on their size. Therefore, the authors' objective was to identify ideal middle cerebral artery (MCA) aneurysm width and neck sizes most suitable for WEB treatment., Methods: The WorldWideWEB consortium is a large multicenter retrospective database that analyzes intracranial aneurysms treated with the WEB device. In this study, all unruptured MCA bifurcation aneurysms with available measurements were included. Cutoff values based on aneurysm width and neck in relation to aneurysm occlusion status were measured using the receiver operating characteristic (ROC) curve. Propensity score matching (PSM) was then used to compare treatment outcomes between aneurysms smaller and larger than the cutoff value for both width and neck size., Results: The ideal cutoff values for MCA bifurcation aneurysm width and neck were 6.1 mm and 4.6 mm, respectively. On PSM, 87 matched pairs were compared based on width size (≤ 6.1 mm and > 6.1 mm), and 77 matched pairs were compared based on neck size (≤ 4.6 mm and > 4.6 mm). There was a significant difference in adequate aneurysm occlusion between aneurysms smaller and larger than those cutoff values for both widths (93% vs 76%, p = 0.0017) and neck sizes (90% vs 70%, p = 0.0026). The retreatment rate was also significantly higher for larger aneurysms in both parameters., Conclusions: This study shows that MCA bifurcation aneurysms ≤ 6.1 mm in width and ≤ 4.6 mm in neck size are significantly better candidates for WEB treatment, leading to improved occlusion status and reduced retreatment rate, which are important considerations when using WEB devices.

Introduction: VEXAS syndrome is a rare condition characterized by somatic mutations in the ubiquitin-like modifier activating enzyme 1 ( UBA1 ) gene and a constellation of clinical/morphologic findings, including the presence of cytoplasmic vacuoles within bone marrow hematopoietic cells., Methods and Objectives: In this report, we present a case of a male patient diagnosed with VEXAS-associated myelodysplastic syndrome following the detection of a non-canonical UBA1 p.Gly477Ala variant whose bone marrow biopsy revealed a conspicuous absence of cytoplasmic vacuolization in hematopoietic cells. This case prompts a comprehensive review of the existing literature on the significance and pathobiology of vacuolization in the context of VEXAS and UBA1 mutations., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Arteriovenous malformations (AVMs) are uncommon cerebral lesions that can cause significant neurological complications. Surgical resection is the gold standard for treatment, but endovascular embolization and stereotactic radiosurgery (SRS) are viable alternatives., Objective: To compare the outcomes of endovascular embolization versus SRS in the treatment of AVMs with Spetzler-Martin grades I-III., Methods: This study combined retrospective data from 10 academic institutions in North America and Europe. Patients aged 1 to 90 years who underwent endovascular embolization or SRS for AVMs with Spetzler-Martin grades I-III between January 2010 and December 2023 were included., Results: The study included 244 patients, including 84 who had endovascular embolization and 160 who had SRS. Before propensity score matching (PSM), complete obliteration at the last follow-up was achieved in 74.5% of the SRS group compared with 57.8% of the embolization group (OR=0.47; 95% CI 0.26 to 0.48; P=0.01). After propensity score matching, SRS still achieved significantly higher occlusion rates at last follow-up (78.9% vs 55.3%; OR=0.32; 95% CI 0.12 to 0.90; P=0.03).Hemorrhagic complications were higher in the embolization group than in the SRS group, although this difference did not reach statistical significance after PSM (13.2% vs 2.6%; OR=5.6; 95% CI 0.62 to 50.47; P=0.12). Similarly, re-treatment rate was higher in the embolization group (10.5% vs 5.3%; OR=2.11; 95% CI 0.36 to 12.31; P=0.40) compared with the SRS group., Conclusion: Our findings indicate that SRS has a significantly higher obliteration rate at last follow-up compared with endovascular embolization. Also, SRS has a higher tendency for fewer hemorrhagic complications and lower re-treatment rate. Further prospective studies are needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high degree of predictability. In patients with persistent symptoms (non-responders), predictability of the neural data remained consistently high. On the other hand, in patients who improved symptomatically (responders), predictability of the neural data was significantly diminished. This neural feature accurately classified clinical status even in patients with limited duration recordings, indicating generalizability that could facilitate therapeutic decision-making., (© 2024. The Author(s).)

Background: Cancer-related deaths for people with human immunodeficiency virus (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and mortality for PWH and cancer. We sought to determine the impact of clonal hematopoiesis (CH) on cancer disparities in PWH., Methods: We conducted a retrospective study to compare the prevalence and clinical outcomes of CH in PWH and people without HIV (PWoH) and cancer. Included in the study were PWH and similar PWoH based on tumor site, age, tumor sequence, and cancer treatment status. Biological aging was also measured using epigenetic methylation clocks., Results: In 136 patients with cancer, PWH had twice the prevalence of CH compared to similar PWoH (23% vs 11%, P = .07). After adjusting for patient characteristics, PWH were 4 times more likely than PWoH to have CH (odds ratio, 4.1 [95% confidence interval, 1.3-13.9]; P = .02). The effect of CH on survival was most pronounced in PWH, who had a 5-year survival rate of 38% if they had CH (vs 59% if no CH), compared to PWoH who had a 5-year survival rate of 75% if they had CH (vs 83% if no CH)., Conclusions: This study provides the first evidence that PWH may have a higher prevalence of CH than PWoH with the same cancers. CH may be an independent biological aging risk factor contributing to inferior survival for PWH and cancer., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Medium vessel occlusion (MeVO) strokes, particularly affecting the M2 segment of the middle cerebral artery, represent a critical proportion of acute ischemic strokes, posing significant challenges in management and outcome prediction. The efficacy of mechanical thrombectomy (MT) in MeVO stroke may warrant reliable predictors of functional outcomes. This study aimed to investigate the prognostic value of follow-up infarct volume (FIV) for predicting 90-day functional outcomes in MeVO stroke patients undergoing MT., Methods: This multicenter, retrospective cohort study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, covering patients with acute ischemic stroke due to M2 segment occlusion treated with MT. We examined the relationship between 90-day functional outcomes, measured by the modified Rankin Scale (mRS), and follow-up infarct volume (FIV), assessed through CT or MRI within 12-36 h post-MT., Results: Among 130 participants, specific FIV thresholds were identified with high specificity and sensitivity for predicting outcomes. A FIV ⩽5 ml was highly specific for predicting favorable and excellent outcomes. The optimal cut-off for both prognostications was identified at ⩽15 ml by the Youden Index, with significant reductions in the likelihood of favorable outcomes observed above a 40 ml threshold. Receiver Operator Curve (ROC) analyses confirmed FIV as a superior predictor of functional outcomes compared to traditional recanalization scores, such as final modified thrombolysis in cerebral infarction score (mTICI). Multivariable analysis further highlighted the inverse relationship between FIV and positive functional outcomes., Conclusions: FIV within 36 h post-MT serves as a potent predictor of 90-day functional outcomes in patients with M2 segment MeVO strokes. Establishing FIV thresholds may aid in the prognostication of stroke outcomes, suggesting a role for FIV in guiding post intervention treatment decisions and informing clinical practice. Future research should focus on validating these findings across diverse patient populations and exploring the integration of FIV measurements with other clinical and imaging markers to enhance outcome prediction accuracy., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation.Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work.Dr. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board); all not directly related to the present work.Dr. Henninger received support from W81XWH-19-PRARP-RPA form the CDMRP/DoD, NS131756 and U24NS113844 from the NINDS, and NR020231 from the NINR and received compensation from Myrobalan, Inc. and General Dynamics during the conduct of this study unrelated to this work.Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical.Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work.Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra.Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work.Dr. Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical, he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular and Stryker Neurovascular, and holds stocks in InNeuroCo, Agile, Perfuze, Galaxy and NTI.Dr. Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally).Dr. Jabbour is a consultant for Medtronic, Microvention and Cerus.

Background: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive steno-occlusive changes in the internal carotid arteries, leading to an abnormal vascular network. Hypertension is prevalent among MMD patients, raising concerns about its impact on disease outcomes. This study aims to compare the clinical characteristics and outcomes of MMD patients with and without hypertension., Methods: We conducted a multicenter, retrospective study involving 598 MMD patients who underwent surgical revascularization across 13 academic institutions in North America. Patients were categorized into hypertensive (n=292) and non-hypertensive (n=306) cohorts. Propensity score matching (PSM) was performed to adjust for baseline differences., Results: The mean age was higher in the hypertension group (46 years vs. 36.8 years, p < 0.001). Hypertensive patients had higher rates of diabetes mellitus (45.2% vs. 10.7%, p < 0.001) and smoking (48.8% vs. 27.1%, p < 0.001). Symptomatic stroke rates were higher in the hypertension group (16% vs. 7.1%; OR: 2.48; 95% CI: 1.39-4.40, p = 0.002) before matching. After PSM, there were no significant differences in symptomatic stroke rates (11.1% vs. 7.7%; OR: 1.5; CI: 0.64-3.47, p = 0.34), perioperative strokes (6.2% vs. 2.1%; OR 3.13; 95% CI: 0.83-11.82, p = 0.09), or good functional outcomes at discharge (93% vs. 92.3%; OR 1.1; 95% CI: 0.45-2.69, p = 0.82)., Conclusion: No significant differences in symptomatic stroke rates, perioperative strokes, or functional outcomes were observed between hypertensive and non-hypertensive Moyamoya patients. Appropriate management can lead to similar outcomes in both groups. Further prospective studies are required to validate these findings., (© 2024. The Author(s).)

Background: Findings from research and recommendations from the World Health Organization favor restrictive use of episiotomy, but whether this guidance is being followed in India, and factors associated with its use, are not known. This study sought to document trends in use of episiotomy over a five-year period (2014-2018); to examine its relationship to maternal, pregnancy, and health-system characteristics; and to investigate its association with other obstetric interventions., Methods: We conducted a secondary analysis of data collected by the Maternal Newborn Health Registry, a prospective population-based pregnancy registry established in Central India (Nagpur, Eastern Maharashtra). We examined type of birth and use of episiotomy in vaginal deliveries from 2014 to 2018, as well as maternal and birth characteristics, health systems factors, and concurrent obstetric interventions associations with its use with multivariable Poisson regression models., Results: During the five-year interval, the rate of episiotomy in vaginal birth rose from 13 to 31% despite a decline in assisted vaginal birth. Associations with episiotomy were found for the following factors: prior birth, multiple gestations, seven or more years of maternal education, higher gestational age, higher birthweight, delivery by an obstetrician (as compared to midwife or general physician), and birth in hospital (as compared to clinic or health center). After adjusting for these factors, year over year rise in episiotomy was significant with an adjusted incidence rate ratio (AIRR) of 1.10 [95% confidence interval (CI) 1.08-1.12; p = 0.002]. We found an association between episiotomy and several other obstetric interventions, with the strongest relationship for maternal treatment with antibiotics (AIRR 4.23, 95% CI 3.12-5.73; p = 0.001)., Conclusions: Episiotomy in this population-based sample from central India steadily rose from 2014 to 2018. This increase over time was observed even after adjusting for patient characteristics, obstetric risk factors, and health system features, such as specialty of the birthing provider. Our findings have important implications for maternal-child health and respectful maternity care given that most women prefer to avoid episiotomy; they also highlight a potential target for antibiotic stewardship as part of global efforts to combat antimicrobial resistance., Trial Registration: The study was registered at ClinicalTrials.gov under reference number NCT01073475., (© 2024. The Author(s).)

Background and Purpose: The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone., Methods: This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage., Results: The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0-1 and 0-2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001)., Conclusion: The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.

Background: While mechanical thrombectomy is considered standard of care for large vessel occlusions, scientific evidence to support treatment for distal and medium vessel occlusions remains scarce., Purpose: To evaluate feasibility, safety, and outcomes in patients with low National Institute of Health Stroke Scale scores undergoing mechanical thrombectomy for treatment of distal medium vessel occlusions., Materials and Methods: Retrospective data review and analysis of prospectively maintained databases at 41 academic centers in North America, Asia, and Europe between January 2017 and January 2022. Characteristics and outcomes were compared between groups with low stroke scale score (≤ 6) versus and higher stroke scale scores (> 6). Propensity score matching using the optimal pair matching method and 1:1 ratio was performed., Results: Data were collected on a total of 1068 patients. After propensity score matching, there were a total of 676 patients included in the final analysis, with 338 patients in each group. High successful reperfusion rates were seen in both groups, 90.2% in ≤ 6 and 88.7% in the > 6 stroke scale groups. The frequency of excellent and good functional outcome was seen more common in low versus higher stroke scale score patients (64.5% and 81.1% versus 39.3% and 58.6%, respectively). The 90-day mortality rate observed in the ≤ 6 stroke scale group was 5.3% versus 13.3% in the > 6 stroke scale group., Conclusion: Mechanical thrombectomy in distal and medium vessel occlusions, specifically in patients with low stroke scale scores is feasible, though it may not necessarily improve outcomes over IVT., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to evaluate the effect of vitamin E on the reproductive responses and the expression of reproductive genes in butter catfish (Ompok bimaculatus). Diets with different levels of vitamin E supplementation (0, 100, and 150 mg/kg) were provided to groups of fish for 60 days. After rearing for 60 days fish were induced with synthetic hormone, that is, Ovatide to study the breeding performance. Ovatide was administrated intramuscularly at the rate of 0.5 and 0.25 mL/kg of body weight for females and males, respectively, in all the treatments. Breeding performance result shows that supplements of vitamin E positively influenced the GSI%, fertilization rate, fecundity, and hatching rate. To understand the relationship between vitamin E and the breeding performance of the fish at the molecular level, a gene expression study was conducted. This study employed real-time PCR for the selected genes critical for reproductive function. In the brain, testis, and ovary dietary vitamin E supplementation of 100 mg/kg significantly enhanced the mRNA transcription of FSHR, Brdt, ESR1, 17beta2, and LHR. Hence, it can be said that 100 mg/kg of vitamin E supplementation in the diet during the reproductive period of O. bimaculatus could improve breeding performance and the mRNA expression of reproductive hormone receptor genes in both males and females of O. bimaculatus., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Background: The comparative efficacy and safety of first-generation flow diverters (FDs), Pipeline Embolization Device (PED) (Medtronic, Irvine, California), Silk (Balt Extrusion, Montmorency, France), Flow Re-direction Endoluminal Device (FRED) (Microvention, Tustin, California), and Surpass Streamline (Stryker Neurovascular, Fremont, California), is not directly established and largely inferred., Purpose: This study aimed to compare the efficacy of different FDs in treating sidewall ICA intracranial aneurysms., Methods: We conducted a retrospective review of prospectively maintained databases from eighteen academic institutions from 2009-2016, comprising 444 patients treated with one of four devices for sidewall ICA aneurysms. Data on demographics, aneurysm characteristics, treatment outcomes, and complications were analyzed. Angiographic and clinical outcomes were assessed using various imaging modalities and modified Rankin Scale (mRS). Propensity score weighting was employed to balance confounding variables. The data analysis used Kaplan-Meier curves, logistic regression, and Cox proportional-hazards regression., Results: While there were no significant differences in retreatment rates, functional outcomes (mRS 0-1), and thromboembolic complications between the four devices, the probability of achieving adequate occlusion at the last follow-up was highest in Surpass device (HR: 4.59; CI: 2.75-7.66, p < 0.001), followed by FRED (HR: 2.23; CI: 1.44-3.46, p < 0.001), PED (HR: 1.72; CI: 1.10-2.70, p = 0.018), and Silk (HR: 1.0 ref. standard). The only hemorrhagic complications were with Surpass (1%)., Conclusion: All the first-generation devices achieved good clinical outcomes and retreatment rates in treating ICA sidewall aneurysms. Prospective studies are needed to explore the nuanced differences between these devices in the long term., Competing Interests: Declarations Conflict of interest A.A. Dmytriw, H.A. Salim, B. Musmar, N.M. Cancelliere, J. Jones, V. Tutino, Z. Hasan, N. Limbucci, S.V. Lay, J. Spears, J.D. Rabinov, M.R. Harrigan, A.H. Siddiqui, E.I. Levy, C.J. Stapleton, L. Renieri, C. Cognard, H. Shaikh, A.L. Kühn, M.A. Möhlenbruch, P. Taussky, F. Settecase, M.K.S. Heran, A. Nguyen, D. Volders, P. Harker, D.A. Devia, M. Psychogios, J.C. Puentes, G. Leone, G. Buono, M. Tarantino, M. Muto, F. Briganti, S. Dalal, V. Gontu, R.E. Alcedo Guardia, J.C. Vicenty-Padilla, P. Brouwer, M.H. Schmidt, C. Schirmer, G.E. Pickett, T. Andersson, M. Söderman, T.R. Marotta, H. Cuellar-Saenz, A.J. Thomas, A.B. Patel, V. Mendes Pereira and N. Adeeb. R.W. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. C.J. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. A.S. Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical, he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular and Stryker Neurovascular, and holds stocks in InNeuroCo, Agile, Perfuze, Galaxy and NTI. S.I. Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally). P. Jabbour is a consultant for Medtronic, Microvention and Cerus. Dr. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board); all not directly related to the present work. Dr. Henninger received support from W81XWH-19-PRARP-RPA form the CDMRP/DoD, NS131756 and U24NS113844 from the NINDS, and NR020231 from the NINR and received compensation from Myrobalan, Inc. and General Dynamics during the conduct of this study unrelated to this work. Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work. Ethical standards The study received approval from the local ethical standards committee at each participating site, and informed consent from patients was waived. The data supporting this study’s findings are available from the corresponding author upon reasonable request., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)