Development of new hormonal male contraception for the couple.

BACKGROUND: Current options for male contraception are limited to condoms, the withdrawal method, or a vasectomy. Studies indicate that men have expressed growing interest in bearing responsibility for family planning. OBJECTIVES: To review prior studies investigating the role of an androgen-only or androgen with progestin regimen for hormonal male contraception and to provide an update of a promising new hormonal agent, a transdermal gel. DISCUSSION: Thus far, there have been six studies conducted in couples evaluating the contraceptive efficacy of an androgen-only or androgen co-administered with a progestin regimen for hormonal male contraception. The only ongoing study is by the National Institute of Child Health and Human Development, in collaboration with the Population Council. They have developed a novel transdermal gel containing testosterone and segesterone acetate (Nestorone), a progestin. An ongoing phase II study enrolling more than 460 couples has shown great potential with respect to the product's efficacy, safety, reversibility, and acceptability. As this agent advances in development, a rapid at-home test for sperm concentration will provide couples with immediate feedback regarding their potential for pregnancy. CONCLUSION: There is promise for the first-of-its-kind hormonal male contraceptive, a transdermal gel, to achieve market approval for distribution in the United States and elsewhere. Its safety, efficacy, reversibility, and user-control are all appealing qualities that make it readily adoptable for clinical practice.

Outcomes of Mechanical Thrombectomy for Patients With Stroke Presenting With Low Alberta Stroke Program Early Computed Tomography Score in Early and Late Time Windows.

BACKGROUND AND OBJECTIVES: This study aimed to compare outcomes of low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) patients with stroke who underwent mechanical thrombectomy (MT) within 6 hours or 6 to 24 hours after stroke onset. METHODS: A retrospective cohort study was conducted using data from a large multicenter international registry from 2013 to 2023. Patients with low ASPECTS (2-5) who underwent MT for anterior circulation intracranial large vessel occlusion were included. A propensity matching analysis was conducted for patients presented in the early (<6 hours) vs late (6-24 hours) time window after symptom onset or last known normal. RESULTS: Among the 10 229 patients who underwent MT, 274 met the inclusion criteria. 122 (44.5%) patients were treated in the late window. Early window patients were older (median age, 74 years [IQR, 63-80] vs 66.5 years [IQR, 54-77]; P < .001), had lower proportion of female patients (40.1% vs 54.1%; P = .029), higher median admission National Institutes of Health Stroke Scale score (20 [IQR, 16-24] vs 19 [IQR, 14-22]; P = .004), and a higher prevalence of atrial fibrillation (46.1% vs 27.3; P = .002). Propensity matching yielded a well-matched cohort of 84 patients in each group. Comparing the matched cohorts showed there was no significant difference in acceptable outcomes at 90 days between the 2 groups (odds ratio = 0.90 [95% CI = 0.47-1.71]; P = .70). However, the rate of symptomatic ICH was significantly higher in the early window group compared with the late window group (odds ratio = 2.44 [95% CI = 1.06-6.02]; P = .04). CONCLUSION: Among patients with anterior circulation large vessel occlusion and low ASPECTS, MT seems to provide a similar benefit to functional outcome for patients presenting <6 hours or 6 to 24 hours after onset.

Impact of Procedure Time on First Pass Effect in Mechanical Thrombectomy for Anterior Circulation Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: First pass effect (FPE) is a metric increasingly used to determine the success of mechanical thrombectomy (MT) procedures. However, few studies have investigated whether the duration of the procedure can modify the clinical benefit of FPE. We sought to determine whether FPE after MT for anterior circulation large vessel occlusion acute ischemic stroke is modified by procedural time (PT). METHODS: A multicenter, international data set was retrospectively analyzed for anterior circulation large vessel occlusion acute ischemic stroke treated by MT who achieved excellent reperfusion (thrombolysis in cerebral infarction 2c/3). The primary outcome was good functional outcome defined by 90-day modified Rankin scale scores of 0-2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. We fit-adjusted logistic regression models and used marginal effects to assess the interaction between PT (≤30 vs >30 minutes) and FPS, adjusting for potential confounders including time from stroke presentation. RESULTS: A total of 1310 patients had excellent reperfusion. These patients were divided into 2 cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and >30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant ( P = .018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs 46.7%, P = .001). However, there was no significant difference in the adjusted predicted probability of good outcome in individuals with PT >30 minutes. This relationship appeared identical in models with PT treated as a continuous variable. CONCLUSION: FPE is modified by PT, with the added clinical benefit lost in longer procedures greater than 30 minutes. A comprehensive metric for MT procedures, namely, FPE 30 , may better represent the ideal of fast, complete reperfusion with a single pass of a thrombectomy device.

A Low-Noise Low-Power 0.001Hz-1kHz Neural Recording System-on-Chip With Sample-Level Duty-Cycling.

Advances in brain-machine interfaces and wearable biomedical sensors for healthcare and human-computer interactions call for precision electrophysiology to resolve a variety of biopotential signals across the body that cover a wide range of frequencies, from the mHz-range electrogastrogram (EGG) to the kHz-range electroneurogram (ENG). Existing integrated wearable solutions for minimally invasive biopotential recordings are limited in detection range and accuracy due to trade-offs in bandwidth, noise, input impedance, and power consumption. This article presents a 16-channel wide-band ultra-low-noise neural recording system-on-chip (SoC) fabricated in 65nm CMOS for chronic use in mobile healthcare settings that spans a bandwidth of 0.001 Hz to 1 kHz through a featured sample-level duty-cycling (SLDC) mode. Each recording channel is implemented by a delta-sigma analog-to-digital converter (ADC) achieving 1.0 µ V rms input-referred noise over 1Hz-1kHz bandwidth with a Noise Efficiency Factor (NEF) of 2.93 in continuous operation mode. In SLDC mode, the power supply is duty-cycled while maintaining consistently low input-referred noise levels at ultra-low frequencies (1.1 µV rms over 0.001Hz-1Hz) and 435 M Ω input impedance. The functionalities of the proposed SoC are validated with two human electrophysiology applications: recording low-amplitude electroencephalogram (EEG) through electrodes fixated on the forehead to monitor brain waves, and ultra-slow-wave electrogastrogram (EGG) through electrodes fixated on the abdomen to monitor digestion.

Cortical depth profiles in primary visual cortex for illusory and imaginary experiences.

Visual illusions and mental imagery are non-physical sensory experiences that involve cortical feedback processing in the primary visual cortex. Using laminar functional magnetic resonance imaging (fMRI) in two studies, we investigate if information about these internal experiences is visible in the activation patterns of different layers of primary visual cortex (V1). We find that imagery content is decodable mainly from deep layers of V1, whereas seemingly 'real' illusory content is decodable mainly from superficial layers. Furthermore, illusory content shares information with perceptual content, whilst imagery content does not generalise to illusory or perceptual information. Together, our results suggest that illusions and imagery, which differ immensely in their subjective experiences, also involve partially distinct early visual microcircuits. However, overlapping microcircuit recruitment might emerge based on the nuanced nature of subjective conscious experience.

Thrombectomy in Stroke Patients With Low Alberta Stroke Program Early Computed Tomography Score: Is Modified Thrombolysis in Cerebral Infarction (mTICI) 2c/3 Superior to mTICI 2b?

BACKGROUND AND PURPOSE: Outcomes following mechanical thrombectomy (MT) are strongly correlated with successful recanalization, traditionally defined as modified Thrombolysis in Cerebral Infarction (mTICI) ≥2b. This retrospective cohort study aimed to compare the outcomes of patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS; 2-5) who achieved mTICI 2b versus those who achieved mTICI 2c/3 after MT. METHODS: This study utilized data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combined databases from 32 thrombectomy-capable stroke centers between 2013 and 2023. The study included only patients with low ASPECTS who achieved mTICI 2b, 2c, or 3 after MT for internal carotid artery or middle cerebral artery (M1) stroke. RESULTS: Of the 10,229 patients who underwent MT, 234 met the inclusion criteria. Of those, 98 (41.9%) achieved mTICI 2b, and 136 (58.1%) achieved mTICI 2c/3. There were no significant differences in baseline characteristics between the two groups. The 90-day favorable outcome (modified Rankin Scale score: 0-3) was significantly better in the mTICI 2c/3 group than in the mTICI 2b group (adjusted odds ratio 2.35; 95% confidence interval [CI] 1.18-4.81; P=0.02). Binomial logistic regression revealed that achieving mTICI 2c/3 was significantly associated with higher odds of a favorable 90-day outcome (odds ratio 2.14; 95% CI 1.07-4.41; P=0.04). CONCLUSION: In patients with low ASPECTS, achieving an mTICI 2c/3 score after MT is associated with a more favorable 90-day outcome. These findings suggest that mTICI 2c/3 is a better target for MT than mTICI 2b in patients with low ASPECTS.

Comparison between transradial and transfemoral mechanical thrombectomy for ICA and M1 occlusions: insights from the Stroke Thrombectomy and Aneurysm Registry (STAR).

BACKGROUND: The role for the transradial approach for mechanical thrombectomy is controversial. We sought to compare transradial and transfemoral mechanical thrombectomy in a large multicenter database of acute ischemic stroke. METHODS: The prospectively maintained Stroke Thrombectomy and Aneurysm Registry (STAR) was reviewed for patients who underwent mechanical thrombectomy for an internal carotid artery (ICA) or middle cerebral artery M1 occlusion. Multivariate regression analyses were performed to assess outcomes including reperfusion time, symptomatic intracerebral hemorrhage (ICH), distal embolization, and functional outcomes. RESULTS: A total of 2258 cases, 1976 via the transfemoral approach and 282 via the transradial approach, were included. Radial access was associated with shorter reperfusion time (34.1 min vs 43.6 min, P=0.001) with similar rates of Thrombolysis in Cerebral Infarction (TICI) 2B or greater reperfusion (87.9% vs 88.1%, P=0.246). Patients treated via a transradial approach were more likely to achieve at least TICI 2C (59.6% vs 54.7%, P=0.001) and TICI 3 reperfusion (50.0% vs 46.2%, P=0.001), and had shorter lengths of stay (mean 9.2 days vs 10.2, P<0.001). Patients treated transradially had a lower rate of symptomatic ICH (8.0% vs 9.4%, P=0.047) but a higher rate of distal embolization (23.0% vs 7.1%, P<0.001). There were no significant differences in functional outcome at 90 days between the two groups. CONCLUSIONS: Radial and femoral thrombectomy resulted in similar clinical outcomes. In multivariate analysis, the radial approach had improved revascularization rates, fewer cases of symptomatic ICH, and faster reperfusion times, but higher rates of distal emboli. Further studies on the optimal approach are necessary based on patient and disease characteristics.

Repeat thrombectomy after large vessel re-occlusion: a propensity score matched analysis of technical and clinical outcomes.

BACKGROUND: Endovascular thrombectomy (EVT) remains the standard of care for acute large vessel occlusion (LVO) stroke. However, the safety and efficacy of repeat thrombectomy (rEVT) in recurrent LVO remains unclear. This study uses a large real-world patient cohort to study technical and clinical outcomes after rEVT. METHODS: This is a retrospective cohort study including patients who underwent thrombectomy between January 2013 and December 2022. Data were included from 21 comprehensive stroke centers globally through the Stroke Thrombectomy and Aneurysm Registry (STAR). Patients undergoing single EVT or rEVT within 30 days of LVO stroke were included in the study. Propensity score matching was used to compare patients undergoing single EVT versus rEVT. RESULTS: Out of a total of 7387 patients who underwent thrombectomy for LVO stroke, 90 (1.2%) patients underwent rEVT for the same vascular territory within 30 days. The median (IQR) time to re-occlusion was 2 (1-7) days. Compared with a matched cohort of patients undergoing a single EVT procedure, patients undergoing rEVT had a comparable rate of good functional outcome and mortality rate, but a higher rate of symptomatic intracranial hemorrhage (sICH). There was a significant reduction in the National Institutes of Health Stroke Scale (NIHSS) score of patients who underwent rEVT at discharge compared with baseline (-4.8±11.4; P=0.006). The rate of successful recanalization was similar in the single thrombectomy and rEVT groups (78% vs 80%, P=0.171) and between index and rEVT performed on the same patient (79% vs 80%; P=0.593). CONCLUSION: Short-interval rEVT is associated with an improvement in the NIHSS score following large vessel re-occlusion. Compared with single thrombectomy, there was a higher rate of sICH with rEVT, but without a significant impact on rates of functional independence or mortality.

Neurosurgery Influences and X: A Social Media Analysis.

BACKGROUND: There exists a complex and ever-evolving relationship between social media and medicine. This study investigates the usage of X (formerly Twitter) among neurosurgeons and explores how virtual engagement potentially impacts this specialty. METHODS: The researchers examined X posts from the top fifty influential neurosurgeons over 6 months. Demographics and practice information were collected. Posts were categorized into 9 predetermined coding definitions. Descriptive statistics were used to summarize user characteristics. χ2 tests and two-tailed T-tests were employed to examine patterns of posting behavior. RESULTS: Most influencers practiced in an academic setting (89%) and 43% of them were age fifty or older. Only 15% identified as female. Cerebrovascular subspecialists accounted for 39% of the cohort. Reposting was the most popular type of posting, constituting 61% of all posts. The most common postcategory observed was "Professional Events" (31%), while "Patient Education" was the least common (0.8%). Private practice and general neurosurgeons infrequently posted about "Professional Events" (5.1%, P < 0.01 and 3.2%, P < 0.01, respectively). "Personal Thoughts" constituted the second most common category, with a notable increase among users younger than 50 (25%, P < 0.01), individuals who identified as female (62%, P < 0.01), those in private practice (69%, P < 0.01), and general neurosurgeons (86%, P < 0.01). CONCLUSIONS: Neurosurgeons of all ages use X to advance their careers and stay updated. However, the utilization of this influential platform likely varies depending on the current practice setting and individual career goals. Neurosurgeons on X appear to have the greatest influence within an academic context, particularly when promoting professional events.

Comparative Outcomes of Mechanical Thrombectomy in Acute Ischemic Stroke Patients with ASPECTS 2-3 vs. 4-5.

BACKGROUND: The influence of Alberta Stroke Program Early CT Score (ASPECTS) on outcomes following mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients with low ASPECTS remains unknown. In this study, we compared the outcomes of AIS patients treated with MT for large vessel occlusion (LVO) categorized by ASPECTS value. METHODS: We conducted a retrospective analysis involving 305 patients with AIS caused by LVO, defined as the occlusion of the internal carotid artery and/or the M1 segments of the middle cerebral artery, stratified into two groups: ASPECTS 2-3 and 4-5. The primary outcome was favorable outcome defined as a 90-day modified Rankin Scale (mRS) score of 0-3. Secondary outcomes were 90-day mRS 0-2, 90-day mortality, any intracerebral hemorrhage (ICH), and symptomatic ICH (sICH). We performed multivariable logistic regression analysis to evaluate the impact of ASPECTS 2-3 vs. 4-5 on outcomes. RESULTS: Fifty-nine patients (19.3%) had ASPECTS 2-3 and 246 (80.7%) had ASPECTS 4-5. Favorable outcomes showed no significant difference between the two groups (adjusted odds ratio [aOR]= 1.13, 95% confidence interval [CI]: 0.52-2.41, p=0.80). There were also no significant differences in 90-day mRS 0-2 (aOR= 1.65, 95% CI: 0.66-3.99, p=0.30), 90-day mortality (aOR= 1.14, 95% CI: 0.58-2.20, p=0.70), any ICH (aOR= 0.54, 95% CI: 0.28-1.00, p=0.06), and sICH (aOR= 0.70, 95% CI: 0.27-1.63, p = 0.40) between the groups. CONCLUSIONS: AIS patients with LVO undergoing MT with ASPECTS 2-3 had similar outcomes compared to ASPECTS 4-5.

Outcomes of mechanical thrombectomy in stroke patients with extreme large infarction core.

BACKGROUND: Recent clinical trials have demonstrated that patients with large vessel occlusion (LVO) and large infarction core may still benefit from mechanical thrombectomy (MT). In this study, we evaluate outcomes of MT in LVO patients presenting with extremely large infarction core Alberta Stroke Program Early CT Score (ASPECTS 0-2). METHODS: Data from the Stroke Thrombectomy and Aneurysm Registry (STAR) was interrogated. We identified thrombectomy patients presenting with an occlusion in the intracranial internal carotid artery (ICA) or M1 segment of the middle cerebral artery and extremely large infarction core (ASPECTS 0-2). A favorable outcome was defined by achieving a modified Rankin scale of 0-3 at 90 days post-MT. Successful recanalization was defined by achieving a modified Thrombolysis In Cerebral Ischemia (mTICI) score ≥2B. RESULTS: We identified 58 patients who presented with ASPECTS 0-2 and underwent MT . Median age was 70.0 (59.0-78.0) years, 45.1% were females, and 202 (36.3%) patients received intravenous tissue plasminogen activator. There was no difference regarding the location of the occlusion (p=0.57). Aspiration thrombectomy was performed in 268 (54.6%) patients and stent retriever was used in 70 (14.3%) patients. In patients presenting with ASPECTS 0-2 the mortality rate was 4.5%, 27.9% had mRS 0-3 at day 90, 66.67% ≥70 years of age had mRS of 5-6 at day 90. On multivariable analysis, age, National Institutes of Health Stroke Scale on admission, and successful recanalization (mTICI ≥2B) were independently associated with favorable outcomes. CONCLUSIONS: This multicentered, retrospective cohort study suggests that MT may be beneficial in a select group of patients with ASPECTS 0-2.

Comparison of balloon guide catheter versus non-balloon guide catheter for mechanical thrombectomy in patients with distal medium vessel occlusion.

BACKGROUND: Several studies have established the safety and efficacy of balloon guide catheters (BGCs) for large vessel occlusions. However, the utility of BGCs remains largely unexplored for distal medium vessel occlusions (DMVOs). In this study, we aim to compare the outcomes of BGC vs. Non-BGC in patients undergoing mechanical thrombectomy (MT) for DMVO. METHOD: This retrospective study from the Stroke Thrombectomy and Aneurysm Registry (STAR) encompassed adult patients with acute anterior cerebral artery, posterior cerebral artery, and middle cerebral artery-M2-3-4 occlusions. Procedure times, safety, recanalization, and neurological outcomes were compared between the two groups, with subgroup analysis based on first-line thrombectomy techniques. RESULTS: A total of 1508 patients were included, with 231 patients (15.3%) in the BGC group and 1277 patients (84.7%) in the non-BGC group. The BGC group had a lower modified Thrombolysis in Cerebral Infarction (mTICI) score ≥2C (43.2% vs 52.7%, P=0.01), longer time from puncture to intracranial access (15 vs 8 min, P<0.01), and from puncture to final recanalization (97 vs 34 min, P<0.01). In the Solumbra subgroup, the first pass effect (FPE) rate was lower in the BGC group (17.4% vs 30.7%, P=0.03). Regarding clinical outcomes, the BGC group had a lower rate of distal embolization (8.8% vs 14.9%, P=0.03). CONCLUSION: Our study found that use of BGC in patients with DMVO was associated with lower mTICI scores, decreased FPE rates, reduced distal embolization, and longer procedure times.

Mechanical thrombectomy for the treatment of primary and secondary anterior cerebral artery occlusions: insights from STAR.

BACKGROUND: The safety and efficacy of mechanical thrombectomy (MT) for the treatment of acute anterior cerebral artery (ACA) occlusions have not clearly been delineated. Outcomes may be impacted based on whether the occlusion is isolated to the ACA (primary ACA occlusion) or occurs in conjunction with other cerebral arteries (secondary). METHODS: We performed a retrospective review of the multicenter Stroke Thrombectomy and Aneurysm (STAR) database. All patients with MT-treated primary or secondary ACA occlusions were included. Baseline characteristics, procedural outcomes, complications, and clinical outcomes were collected. Primary and secondary ACA occlusions were compared using the Mann-Whitney U test and Kruskal-Willis test for continuous variables and the χ2 test for categorical variables. RESULTS: The study cohort comprised 238 patients with ACA occlusions (49.2% female, median (SD) age 65.6 (16.7) years). The overall rate of successful recanalization was 75%, 90-day good functional outcome was 23%, and 90-day mortality was 35%. There were 44 patients with a primary ACA occlusion and 194 patients with a secondary ACA occlusion. When adjusted for baseline variables, the rates of successful recanalization (68% vs 76%, P=0.27), 90-day good functional outcome (41% vs 19%, P=0.38), and mortality at 90 days (25% vs 38%, P=0.12) did not differ between primary and secondary ACA occlusion groups. CONCLUSION: Clinical and procedural outcomes are similar between MT-treated primary and secondary ACA occlusions for select patients. Our findings demonstrate the need for established criteria to determine ideal patient and ACA stroke characteristics amenable to MT treatment.

Comprehensive analysis of the impact of procedure time and the 'golden hour' in subpopulations of stroke thrombectomy patients.

OBJECTIVE: To evaluate the effect of procedure time on thrombectomy outcomes in different subpopulations of patients undergoing endovascular thrombectomy (EVT), given the recently expanded indications for EVT. METHODS: This multicenter study included patients undergoing EVT for acute ischemic stroke at 35 centers globally. Procedure time was defined as time from groin puncture to successful recanalization (Thrombolysis in Cerebral Infarction score ≥2b) or abortion of procedure. Patients were stratified based on stroke location, use of IV tissue plasminogen activator (tPA), Alberta Stroke Program Early CT score, age group, and onset-to-groin time. Primary outcome was the 90-day modified Rankin Scale (mRS) score, with scores 0-2 designating good outcome. Secondary outcome was postprocedural symptomatic intracranial hemorrhage (sICH). Multivariate analyses were performed using generalized linear models to study the impact of procedure time on outcomes in each subpopulation. RESULTS: Among 8961 patients included in the study, a longer procedure time was associated with higher odds of poor outcome (mRS score 3-6), with 10% increase in odds for each 10 min increment. When procedure time exceeded the 'golden hour', poor outcome was twice as likely. The golden hour effect was consistent in patients with anterior and posterior circulation strokes, proximal or distal occlusions, in patients with large core infarcts, with or without IV tPA treatment, and across age groups. Procedures exceeding 1 hour were associated with a 40% higher sICH rate. Posterior circulation strokes, delayed presentation, and old age were the variables most sensitive to procedure time. CONCLUSIONS: In this work we demonstrate the universality of the golden hour effect, in which procedures lasting more than 1 hour are associated with worse clinical outcomes and higher rates of sICH across different subpopulations of patients undergoing EVT.

Recurrence of a large intracranial fusiform aneurysm treated with overlapping Pipeline embolization devices: illustrative case.

BACKGROUND: Flow diversion, specifically with the Pipeline embolization device (PED), represents a paradigm shift in the treatment of intracranial aneurysms. Several studies have demonstrated its efficacy and at times superiority to conventional treatment modalities for aneurysms with a fusiform morphology, giant size, or wide neck. However, there may be a nonsignificant risk of recurrence after flow diversion of these historically difficult-to-treat aneurysms, relative to aneurysms with a more favorable morphology and size (i.e., saccular, narrow necked). To date, only three papers in the literature have demonstrated the recurrence of a completely occluded aneurysm on follow-up. OBSERVATIONS: The authors describe a patient with a giant middle cerebral artery fusiform aneurysm treated with multiple telescoping PEDs. On the 3-month follow-up angiogram, there was complete occlusion of the aneurysm. The patient was lost to follow-up and presented 4 years later with a recurrence of the aneurysm between PED segments, requiring retreatment. The patient represented 3 years posttreatment with the need for repeat treatment of the fusiform aneurysm due to separation of the existing PEDs along with stent reconstruction. At the 20-month follow-up after the third treatment, the initial aneurysm target was found to be occluded. LESSONS: This case illustrates the need for long-term follow-up, specifically for patients with giant wide-necked or fusiform aneurysms treated with overlapping PEDs.

Novel progestogenic androgens for male contraception: design, synthesis, and activity of C7 α-substituted testosterone†.

Male contraceptive development has included use of testosterone (T) with or without a progestin or the use of a single molecule such as progestogenic androgens (PA) for suppression of testicular T production. Expanding upon the vast amount of data accumulated from nortestosterone (NT), NT analogs, and their prodrugs, a new series of PA, the C7 methyl, and ethyl α-substituted T analogs 7α-Methyltestosterone (7α-MT) and 7α-Ethyltestosterone (7α-ET), respectively, were hypothesized and designed to have superior androgenic and progestogenic activities when compared with parent T. Results from androgen receptor and progesterone receptor competitive binding and transcriptional activation assays showed favorable activities for these T analogs. Additionally, 7α-MT and 7α-ET were shown to be active substrates for aromatase in vitro, mitigating a potential negative impact on bone mineral density with long-term use. In conjunction with this observation, the diminished metabolism of these T analogs by 5α-reductase may reduce potential concerns for prostatic growth. In the Hershberger in vivo rat bioassay, 7α-MT and 7α-ET showed superior androgenic and anabolic activities as compared with T. These C7 α-substituted T analogs also showed clear progestogenic activity in the McPhail bioassay which evaluated endometrial glandular arborization in a rabbit model. The discovery of aromatizable molecules with reduced metabolism by 5α-reductase that have androgenic, anabolic, and progestogenic properties indicates that the core and/or prodrugs of 7α-MT and 7α-ET are promising molecules for further development as male contraceptive PAs.

The effect of occlusion location and technique in mechanical thrombectomy for minor stroke.

INTRODUCTION: Endovascular mechanical thrombectomy (MT) is an established treatment for large vessel occlusion strokes with a National Institutes of Health Stroke Scale (NIHSS) score of 6 or higher. Data pertaining to minor strokes, medium, or distal vessel occlusions, and most effective MT technique is limited and controversial. METHODS: A multicenter retrospective study of all patients treated with MT presenting with NIHSS score of 5 or less at 29 comprehensive stroke centers. The cohort was dichotomized based on location of occlusion (proximal vs. distal) and divided based on MT technique (direct aspiration first-pass technique [ADAPT], stent retriever [SR], and primary combined [PC]). Outcomes at discharge and 90 days were compared between proximal and distal occlusion groups, and across MT techniques. RESULTS: The cohort included 759 patients, 34% presented with distal occlusion. Distal occlusions were more likely to present with atrial fibrillation (p = 0.008) and receive IV tPA (p = 0.001). Clinical outcomes at discharge and 90 days were comparable between proximal and distal groups. Compared to SR, patients managed with ADAPT were more likely to have a modified Rankin Scale of 0-2 at discharge and at 90 days (p = 0.024 and p = 0.013). Primary combined compared to ADAPT, prior stroke, multiple passes, older age, and longer procedure time were independently associated with worse clinical outcome, while successful recanalization was positively associated with good clinical outcomes. CONCLUSIONS: Proximal and distal occlusions with low NIHSS have comparable outcomes and safety profiles. While all MT techniques have a similar safety profile, ADAPT was associated with better clinical outcomes at discharge and 90 days.

Choroid plexus arteriovenous malformations: A systematic review.

To systematically review the reported outcomes and complications of different treatment options for choroid plexus arteriovenous malformations (AVMs), specifically focusing on surgical resection and endovascular embolization. A systematic literature review was performed using a PubMed query for studies published between January 1975 and July 2021. All studies describing the clinical presentation, management, and outcome of confirmed choroid plexus AVM cases were included. A total of 20 studies were included in the final analysis. Of these, 18 were singlepatient case reports, one article contained two patients, and a single study was a cohort of 24 patients. Patient age ranged from one day to 61 years, with a mean of 31.8±20.4 years. Most choroid plexus AVMs were located in the lateral ventricles (14 patients, 70.0%), while there were four (20.0%) located in the third ventricle, and two in the fourth ventricle (10.0%). Almost all patients were treated with surgical resection (18 patients, 90%). In 14 patients (77.8%), complete resection of the AVM was achieved. A residual AVM was reported in one case (5.6%). Most patients were reported to have improved from their presentation status over time (14 patients, 70.0%). Presence or absence of long-term sequelae (e.g., neurologic deficits) were reported for 14 patients (70%). Eleven of these patients (78.6%) were reported to have no neurological sequelae. While data on choroid plexus AVMs remains limited, the available evidence suggests gross total resection of lesions in this location can be safely achieved with subsequent reduction in preoperative symptoms.

Preclinical models of middle cerebral artery occlusion: new imaging approaches to a classic technique.

Stroke remains a major burden on patients, families, and healthcare professionals, despite major advances in prevention, acute treatment, and rehabilitation. Preclinical basic research can help to better define mechanisms contributing to stroke pathology, and identify therapeutic interventions that can decrease ischemic injury and improve outcomes. Animal models play an essential role in this process, and mouse models are particularly well-suited due to their genetic accessibility and relatively low cost. Here, we review the focal cerebral ischemia models with an emphasis on the middle cerebral artery occlusion technique, a "gold standard" in surgical ischemic stroke models. Also, we highlight several histologic, genetic, and in vivo imaging approaches, including mouse stroke MRI techniques, that have the potential to enhance the rigor of preclinical stroke evaluation. Together, these efforts will pave the way for clinical interventions that can mitigate the negative impact of this devastating disease.

Mechanical thrombectomy for treatment of acute ischemic stroke in frail patients: a systematic review of the literature.

BACKGROUND: The overall safety and efficacy of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) in frail patients is not well delineated. This systematic review aims to summarize and compare outcomes in frail and non-frail patients who underwent MT for AIS. METHODS: A systematic review of the literature was performed using PubMed, Ovid Medline, and Web of Science to identify studies with outcomes-related data for frail patients with MT-treated AIS. The recanalization rate, procedural complications, and clinical outcome at 90-day follow-up were collected. RESULTS: In the four included studies there were 642 frail patients and 499 non-frail patients. Frail patients had reduced rates of good functional outcomes (29% vs 42%; χ2=22, p<0.01) and increased 90-day mortality (51% vs 25%; χ2=38, p<0.01) compared with non-frail patients. CONCLUSION: MT for treatment of AIS in frail patients may be associated with worse rates of morbidity and mortality along with reduced efficacy. Given that no studies to date directly compare conservative measures with endovascular management for AIS in frail patients, more studies are required to further evaluate and identify characteristics that may improve outcomes in these patients.