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Increasing survival rates of children following cancer treatment have resulted in a significant population of adult survivors with the common side effect of infertility. Additionally, the availability of genetic testing has identified Klinefelter syndrome (classic 47,XXY) as the cause of future male infertility for a significant number of prepubertal patients. This study explores new spermatogonia stem cell (SSC)-based fertility therapies to meet the needs of these patients. Testicular cells were isolated from cryopreserved human testes tissue stored from XY and XXY prepubertal patients and propagated in a two-dimensional culture. Cells were then incorporated into a 3D human testicular organoid (HTO) system. During a 3-week culture period, HTOs maintained their structure, viability, and metabolic activity. Cell-specific PCR and flow cytometry markers identified undifferentiated spermatogonia, Sertoli, Leydig, and peritubular cells within the HTOs. Testosterone was produced by the HTOs both with and without hCG stimulation. Upregulation of postmeiotic germ cell markers was detected after 23 days in culture. Fluorescence in situ hybridization (FISH) of chromosomes X, Y, and 18 identified haploid cells in the in vitro differentiated HTOs. Thus, 3D HTOs were successfully generated from isolated immature human testicular cells from both euploid (XY) and Klinefelter (XXY) patients, supporting androgen production and germ cell differentiation in vitro.

Background: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines., Methods: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation., Findings: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p<0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p<0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile., Interpretation: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction., Competing Interests: Competing interests: TNN: PI CLEAR study (Medtronic). DCH: Stryker, Vesalio, Cerenovus consultant. AEH: consultant and speaker for Medtronic, Stryker, Microvention, Penumbra, Balt, Scientia, Genentech and GE Healthcare. PJ: Medtronic, Microvention, Balt, Cerenovus consultant. SO-G: Medtronic, Stryker consultant. DSL: Cerenovus, Genentech, Stryker, Medtronic consultant. TGJ: advisor/investor for Anaconda, Route92, FreeOx, and Blockade Medical; Medtronic grants, DAWN, AURORA PI (Stryker). WJM: consultant: Rebound Therapeutics, Viseon Imperative Care, Q’Apel, Stryker, Stream Biomedical, Spartan Micro; Investor: Cerebrotech, Endostream, Q’Apel, Viseon, Rebound, and Spartan Micro. RGN: Stryker; Cerenovus/Neuravi; Anaconda, Cerebrotech, Ceretrieve, Vesalio (Advisory Board); Imperative Care., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide., Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior)., Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers., Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions., Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.

Currently several endovascular modalities and devices are available for use in acute ischemic stroke setting. Limited data exist regarding the relative efficacy of these different options when used individually or in combination. The primary objective of this study was to retrospectively compare the recanalization rates of various endovascular options when used for the treatment of acute ischemic stroke in the anterior cerebral circulation. We retrospectively reviewed 132 consecutive patients treated endovascularly at our center for acute ischemic stroke in the anterior cerebral circulation. Recanalization was defined as mTIMI of ≥ 2 while complete recanalization was defined as mTIMI of 4. Statistical analysis was performed to determine the modality or combination of modalities associated with best recanalization rate. Recanalization was achieved in 74% of patients while complete recanalization was achieved in 39% of patients. No individual endovascular therapy was significantly different from others in achieving recanalization. Where a multimodality approach was used, combination of angioplasty with intra- or extracranial stent placement was significantly (p=0.05) associated with recanalization. On regression analysis, combination of intra-arterial tPA with a mechanical modality (p=0.09) was significantly associated with recanalization while combination of intravenous tPA with intracranial stent placement (p=0.06) was significantly associated with complete recanalization. Combination of pharmacological and mechanical modalities in the setting of multimodal therapy is associated with increased likelihood of successful recanalization in patients with acute ischemic stroke in the anterior cerebral circulation. Stent placement in acute stroke setting is promising and needs further exploration. Further prospective studies are needed.

Thrombolytic and antithrombotic agents form the cornerstone of stroke treatment and prevention. Recombinant tissue plasminogen activation (rt-PA) improves the outcome in patients treated within 3 hours of stroke onset. The risk-benefit ratio is narrow because of an increased risk for bleeding, but studies do not support a higher risk in the geriatric population. Emerging trials are directed at extending the therapeutic window and identifying agents that could provide better safety profiles. Large randomized trials have also highlighted the effectiveness and safety of early and continuous antiplatelet therapy in reducing atherothrombotic stroke recurrence. Aspirin has become the antiplatelet treatment standard against which several other antiplatelet agents have been shown to be more effective. The prevention of cardioembolic stroke is best accomplished with oral anticoagulation, barring any contraindications.