A universal urinary cell gene signature of acute rejection in kidney allografts.

INTRODUCTION: Acute rejection (AR) undermines the life-extending benefits of kidney transplantation and is diagnosed using the invasive biopsy procedure. T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), or concurrent TCMR + ABMR (Mixed Rejection [MR]) are the three major types of AR. Development of noninvasive biomarkers diagnostic of AR due to any of the three types is a useful addition to the diagnostic armamentarium. METHODS: We developed customized RT-qPCR assays and measured urinary cell mRNA copy numbers in 145 biopsy-matched urine samples from 126 kidney allograft recipients. We determined whether the urinary cell three-gene signature diagnostic of TCMR (Suthanthiran et al., 2013) discriminates patients with no rejection biopsies (NR, n = 50) from those with ABMR (n = 28) or MR (n = 20) biopsies. RESULTS: The urinary cell three-gene signature discriminated all three types of rejection biopsies from NR biopsies (P < 0.0001, One-way ANOVA). Dunnett's multiple comparisons test yielded P < 0.0001 for NR vs. TCMR; P < 0.001 for NR vs. ABMR; and P < 0.0001 for NR vs. MR. By bootstrap resampling, optimism-corrected area under the receiver operating characteristic curve (AUC) was 0.749 (bias-corrected 95% confidence interval [CI], 0.638 to 0.840) for NR vs. TCMR (P < 0.0001); 0.780 (95% CI, 0.656 to 0.878) for NR vs. ABMR (P < 0.0001); and 0.857 (95% CI, 0.727 to 0.947) for NR vs. MR (P < 0.0001). All three rejection categories were distinguished from NR biopsies with similar accuracy (all AUC comparisons P > 0.05). CONCLUSION: The urinary cell three-gene signature score discriminates AR due to TCMR, ABMR or MR from NR biopsies in human kidney allograft recipients.

Validation of the transcranial Doppler rescue criteria for mechanical thrombectomy.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) identifies acute stroke patients with arterial occlusion where treatment may not effectively open the blocked vessel. This study aimed to examine the clinical utility and prognostic value of TCD flow findings in patients enrolled in a multicenter prospective study (CLOTBUST-PRO). METHODS: Patients enrolled with intracranial occlusion on computed tomography angiography (CTA) who underwent urgent TCD evaluation before intravenous thrombolysis was included in this analysis. TCD findings were assessed using the mean flow velocity (MFV) ratio, comparing the reciprocal ratios of the middle cerebral artery (MCA) depths bilaterally (affected MCA-to-contralateral MCA MFV [aMCA/cMCA MFV ratio]). RESULTS: A total of 222 patients with intracranial occlusion on CTA were included in the study (mean age: 64 ± 14 years, 62% men). Eighty-eight patients had M1 MCA occlusions; baseline mean National Institutes of Health Stroke Scale (NIHSS) score was 16, and a 24-hour mean NIHSS score was 10 points. An aMCA/cMCA MFV ratio of <.6 had a sensitivity of 99%, specificity of 16%, positive predictive value (PV) of 60%, and negative PV of 94% for identifying large vessel occlusion (LVO) including M1 MCA, terminal internal carotid artery, or tandem ICA/MCA. Thrombolysis in Brain Ischemia scale, with (grade ≥1) compared to without flow (grade 0), showed a sensitivity of 17.1%, specificity of 86.9%, positive PV of 62%, and negative PV of 46% for identifying LVO. CONCLUSIONS: TCD is a valuable modality for evaluating arterial circulation in acute ischemic stroke patients, demonstrating significant potential as a screening tool for intravenous/intra-arterial lysis protocols.

Patent foramen ovale closure in ischemic stroke patients with and without thrombophilia: a systematic review and meta-analyses.

Ischemic stroke patients with thrombophilia and patient foramen ovale (PFO) may have an increased risk of recurrent stroke and transient ischemic attack (TIA), and may benefit from PFO closure. However, screening for thrombophilia is not routinely performed and the impact of thrombophilia on prognosis after PFO closure is uncertain. We aim to compare the risk of recurrent stroke and TIA after PFO closure in patients with thrombophilia versus those without. We performed a systematic review and meta-analyses of the literature, with a comprehensive literature search performed on 12 January 2023. Studies comparing the outcomes of patients with and without thrombophilia after PFO closure were included. The primary outcome evaluated was a recurrence of acute cerebrovascular event (ACE), a composite of recurrent ischemic stroke and recurrent TIA. The secondary outcomes included recurrent ischemic stroke only or TIA only. A total of 8 cohort studies were included, with a total of 3514 patients. There was an increased risk of stroke/TIA in patients with thrombophilia compared to those without thrombophilia after PFO (OR: 1.42, 95% CI: 1.01-1.99, I2 = 50%). The association between risk of TIA only (OR: 1.36, 95% CI: 0.77-2.41, I2 = 0%) and stroke only (OR: 1.09, 95% CI: 0.54-2.21, I2 = 0%) with thrombophilia did not reach statistical significance. There is an increased risk of recurrent cerebral ischemia event in patients with thrombophilia compared to those without thrombophilia after PFO closure. Future large prospective studies are necessary to characterise the risk and benefits of PFO closure, as well as the appropriate medical treatment to reduce the risk of recurrent stroke and TIA in this high-risk population.

Bilateral Takayasu's retinopathy as the initial presentation of Takayasu's arteritis.

We present a case of Takayasu's arteritis in a woman in her 30s, who exhibited visual symptoms and ophthalmic manifestations of the disease, specifically Takayasu's retinopathy stage 4, in both eyes. Despite severe narrowing of all branches of the aortic arch and compromised perfusion in both upper limbs, she had no history of intermittent claudication. Doppler study and CT angiography revealed diffuse circumferential wall thickening of bilateral common carotid, subclavian and axillary arteries. Treatment involved retinal laser photocoagulation and immune suppression. This case underscores that advanced Takayasu's retinopathy can be an initial presentation of Takayasu's arteritis even in a state of severely compromised peripheral limb circulation.

Outcomes of Decompressive Surgery for Patients With Severe Cerebral Venous Thrombosis: DECOMPRESS2 Observational Study.

BACKGROUND: Decompressive neurosurgery is recommended for patients with cerebral venous thrombosis (CVT) who have large parenchymal lesions and impending brain herniation. This recommendation is based on limited evidence. We report long-term outcomes of patients with CVT treated by decompressive neurosurgery in an international cohort. METHODS: DECOMPRESS2 (Decompressive Surgery for Patients With Cerebral Venous Thrombosis, Part 2) was a prospective, international cohort study. Consecutive patients with CVT treated by decompressive neurosurgery were evaluated at admission, discharge, 6 months, and 12 months. The primary outcome was death or severe disability (modified Rankin Scale scores, 5-6) at 12 months. The secondary outcomes included patient and caregiver opinions on the benefits of surgery. The association between baseline variables before surgery and the primary outcome was assessed by multivariable logistic regression. RESULTS: A total of 118 patients (80 women; median age, 38 years) were included from 15 centers in 10 countries from December 2011 to December 2019. Surgery (115 craniectomies and 37 hematoma evacuations) was performed within a median of 1 day after diagnosis. At last assessment before surgery, 68 (57.6%) patients were comatose, fixed dilated pupils were found unilaterally in 27 (22.9%) and bilaterally in 9 (7.6%). Twelve-month follow-up data were available for 113 (95.8%) patients. Forty-six (39%) patients were dead or severely disabled (modified Rankin Scale scores, 5-6), of whom 40 (33.9%) patients had died. Forty-two (35.6%) patients were independent (modified Rankin Scale scores, 0-2). Coma (odds ratio, 2.39 [95% CI, 1.03-5.56]) and fixed dilated pupil (odds ratio, 2.22 [95% CI, 0.90-4.92]) were predictors of death or severe disability. Of the survivors, 56 (78.9%) patients and 61 (87.1%) caregivers expressed a positive opinion on surgery. CONCLUSIONS: Two-thirds of patients with severe CVT were alive and more than one-third were independent 1 year after decompressive surgery. Among survivors, surgery was judged as worthwhile by 4 out of 5 patients and caregivers. These results support the recommendation to perform decompressive neurosurgery in patients with CVT with impending brain herniation.

Central Retinal Artery Occlusion in Young Adults at High Altitude: Thin Air, High Stakes.

Rana, Vipin, Pradeep Kumar, Sandeepan Bandopadhyay, Vijay K. Sharma, Meenu Dangi, Dattakiran Joshi, Sanjay Kumar Mishra, Satyabrat Srikumar, and V.A. Arun. Central retinal artery occlusion in young adults at high altitude: thin air, high stakes. High Alt Med Biol. 00:000-000, 2024.-We present five cases of young security personnel who were posted at high altitude (HA) for a duration of at least 6 months and presented with a sudden decrease of vision in one eye. The diagnosis of central retinal artery occlusion (CRAO) was made in all patients. Fundus fluorescein angiography and optical coherence tomography of the macula supported the diagnosis. None of these cases had any preexisting comorbidities. Erythrocytosis was noticed in all patients, and two of them had hyperhomocysteinemia. Four out of five patients showed either middle cerebral artery or internal carotid artery (ICA) thrombosis on computed tomography angiography. The patients were managed by a team of ophthalmologist, hematologist, vascular surgeon, and neurologist. In cases of incomplete ICA occlusion, patients were managed surgically. However, in the case of complete ICA occlusion, management was conservative with antiplatelet drugs. This case series highlights HA-associated erythrocytosis and hyperhomocysteinemia as important risk factors for CRAO in young individuals stationed at HA.

Use of wearable technology in cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source: a systematic review.

INTRODUCTION: Prolonged cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source (ESUS) is necessary to identify atrial fibrillation (AF) that requires anticoagulation. Wearable devices may improve AF detection compared to conventional management. We aimed to review the evidence for the use of wearable devices in post-cryptogenic stroke and post-ESUS monitoring. METHODS: We performed a systematic search of PubMed, EMBASE, Scopus and clinicaltrials.gov on 21 July 2022, identifying all studies that investigated the use of wearable devices in patients with cryptogenic stroke or ESUS. The outcomes of AF detection were analysed. Literature reports on electrocardiogram (ECG)-based (external wearable, handheld, patch, mobile cardiac telemetry [MCT], smartwatch) and photoplethysmography (PPG)-based (smartwatch, smartphone) devices were summarised. RESULTS: A total of 27 relevant studies were included (two randomised controlled trials, seven prospective trials, 10 cohort studies, six case series and two case reports). Only four studies compared wearable technology to Holter monitoring or implantable loop recorder, and these studies showed no significant differences on meta-analysis (odds ratio 2.35, 95% confidence interval [CI] 0.74-7.48, I 2 = 70%). External wearable devices detected AF in 20.7% (95% CI 14.9-27.2, I 2 = 76%) of patients and MCT detected new AF in 9.6% (95% CI 7.4%-11.9%, I 2 = 56%) of patients. Other devices investigated included patch sensors, handheld ECG recorders and PPG-based smartphone apps, which demonstrated feasibility in the post-cryptogenic stroke and post-ESUS setting. CONCLUSION: Wearable devices that are ECG or PPG based are effective for paroxysmal AF detection after cryptogenic stroke and ESUS, but further studies are needed to establish how they compare with Holter monitors and implantable loop recorder.

Left Ventricular Diastolic Dysfunction Is Associated with Poor Functional Outcomes after Endovascular Thrombectomy.

INTRODUCTION: With the advent of endovascular thrombectomy (ET), patients with acute ischaemic strokes (AIS) with large vessel occlusion (LVO) have seen vast improvements in treatment outcomes. Left ventricular diastolic dysfunction (LVDD) has been shown to herald poorer prognosis in conditions such as myocardial infarction. However, whether LVDD is related to functional recovery and outcomes in ischaemic stroke remains unclear. We studied LVDD for possible relation with clinical outcomes in patients with LVO AIS who underwent ET. METHODS: We studied a retrospective cohort of 261 LVO AIS patients who had undergone ET at a single comprehensive stroke centre and correlated LVDD to short-term mortality (in-hospital death) as well as good functional recovery defined as modified Rankin Scale of 0-2 at 3 months. RESULTS: The study population had a mean age of 65-years-old and were predominantly male (54.8%). All of the patients underwent ET with 206 (78.9%) achieving successful reperfusion. Despite this, 25 (9.6%) patients demised during the hospital admission and 149 (57.1%) did not have good function recovery at 3 months. LVDD was present in 82 (31.4%) patients and this finding indicated poorer outcomes in terms of functional recovery at 3 months (OR 2.18, 95% CI 1.04-4.54, p = 0.038) but was not associated with increased in-hospital mortality (OR 2.18, 95% CI 0.60-7.99, p = 0.240) after adjusting for various confounders. CONCLUSION: In addition to conventional echocardiographic indices such as left ventricular ejection fraction, LVDD may portend poorer outcomes after ET, and this relationship should be investigated further.

Cerebral Haemodynamic Changes in Type 2 Diabetes Mellitus Following a Three-Month Yoga Intervention: A Randomized Controlled Trial.

Background and purpose Cerebral haemodynamics and cognitive performance may be adversely affected in type 2 diabetes mellitus (T2DM). Previous studies reported reduced cerebral blood flow (CBF) and altered cerebrovascular reactivity (CVR) in T2DM. Yoga, an ancient holistic health approach, is known to be beneficial for T2DM. We hypothesized that yoga practice may alter CBF and the flow resistance in the middle cerebral artery (MCA) and improve cognition in T2DM. Our secondary objective was to explore the relationship between changes in cerebral haemodynamics and cognition in T2DM. Materials and methods Participants were randomly allotted into the yoga and control groups based on the eligibility criteria. One hour of yoga intervention specific to type 2 diabetes was provided to the yoga group for three months, while conventional treatment was provided to the control group. A transcranial Doppler was used to evaluate longitudinal changes in cerebral haemodynamics in MCA. A Corsi block tapping test was used to assess visio-spatial working memory. Results There were 75 participants recruited, of whom 38 participated in yoga and 37 participated in a control group. Both intention to treat and per protocol analysis showed significant results. At day 90, intention-to-treat analysis showed significant changes in CBF velocities (mean difference -10.85%, 95% CI (-13.26, -6.15), p<0.001), cerebral vasodilatory reserve (mean difference -0.23%, 95% CI (-0.43, -0.03), p=0.02) and cognition (mean difference -12.13%, 95% CI (-17.48, -6.78), p≤0.001). There was no between-group effect. Also, the correlation between the CBF and cognition did not show any significant results. Conclusion The three-month yoga intervention was associated with an improvement in cerebral hemodynamics. The study also revealed an improvement in visio-spatial working memory among patients with T2DM. The study did not show any correlation between the improvement in cerebral haemodynamics and working memory. We recommend larger and longer studies on yoga intervention for T2DM patients to evaluate whether such benefits are sustained and improve their quality of life.

RNA-sequencing of Human Kidney Allografts and Delineation of T-Cell Genes, Gene Sets, and Pathways Associated With Acute T Cell-mediated Rejection.

BACKGROUND: Delineation of T-cell genes, gene sets, pathways, and T-cell subtypes associated with acute T cell-mediated rejection (TCMR) may improve its management. METHODS: We performed bulk RNA-sequencing of 34 kidney allograft biopsies (16 Banff TCMR and 18 no rejection [NR] biopsies) from 34 adult recipients of human kidneys. Computational analysis was performed to determine the differential intragraft expression of T-cell genes at the level of single-gene, gene set, and pathways. RESULTS: T-cell signaling pathway gene sets for plenary T-cell activation were overrepresented in TCMR biopsies compared with NR biopsies. Heightened expression of T-cell signaling genes was validated using external TCMR biopsies. Pro- and anti-inflammatory immune gene sets were enriched, and metabolism gene sets were depleted in TCMR biopsies compared with NR biopsies. Gene signatures of regulatory T cells, Th1 cells, Th2 cells, Th17 cells, T follicular helper cells, CD4 tissue-resident memory T cells, and CD8 tissue-resident memory T cells were enriched in TCMR biopsies compared with NR biopsies. T-cell exhaustion and anergy were also molecular attributes of TCMR. Gene sets associated with antigen processing and presentation, and leukocyte transendothelial migration were overexpressed in TCMR biopsies compared with NR biopsies. Cellular deconvolution of graft infiltrating cells by gene expression patterns identified CD8 T cell to be the most abundant T-cell subtype infiltrating the allograft during TCMR. CONCLUSIONS: Our delineation of intragraft T-cell gene expression patterns, in addition to yielding new biological insights, may help prioritize T-cell genes and T-cell subtypes for therapeutic targeting.

Transcranial Doppler ultrasonography in bacterial meningitis: A systematic review.

PURPOSE: Bacterial meningitis remains a global threat due to its high mortality. It is estimated that >1.2 million cases of bacterial meningitis are reported annually. Intracranial vasculopathy is an important, under-documented complication, easily detected by transcranial Doppler (TCD) ultrasonography. Following the PRISMA Guidelines, we reviewed the utility of TCD in bacterial meningitis. METHODS: This is a systematic review of observational studies on the use of TCD in patients with CSF-proven bacterial meningitis. Characteristic changes in TCD parameters along the course of the disease, correlation of TCD findings with neuroimaging, and functional outcomes were evaluated. RESULTS: Nine studies were included with a total of 492 participants (mean age of 42). The most common TCD finding was intracranial arterial stenosis of the MCA (50%-82%) and ischemia (33%) was the predominant neuroimaging finding. The presence of an abnormal TCD finding increased the risk of poor outcomes as high as 70%. CONCLUSIONS: Patients diagnosed with bacterial meningitis who underwent TCD show alterations in cerebral blood flow, correlating with imaging findings and poor outcomes. It aids in the diagnosis of its sequelae and can predict the prognosis of its outcome. TCD is a cost-effective, reliable modality for diagnosing vasculopathy associated with bacterial meningitis. It may prove useful in our armamentarium of management. Large prospective studies with long-term follow-up data may help establish the use of TCD in bacterial meningitis.

Transcriptomic signatures of chronic active antibody-mediated rejection deciphered by RNA sequencing of human kidney allografts.

Natural killer (NK) cells mediate spontaneous cell-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity. This dual functionality could enable their participation in chronic active antibody-mediated rejection (CA-ABMR). Earlier microarray profiling studies have not subcategorized antibody-mediated rejection into CA-ABMR and active-ABMR, and the gene expression pattern of CA-ABMR has not been compared with that of T cell-mediated rejection (TCMR). To fill these gaps, we RNA sequenced human kidney allograft biopsies categorized as CA-ABMR, active-ABMR, TCMR, or No Rejection (NR). Among the 15,910 genes identified in the biopsies, 60, 114, and 231 genes were uniquely overexpressed in CA-ABMR, TCMR, and active-ABMR, respectively; compared to NR, 50 genes were shared between CA-ABMR and active-ABMR, and 164 genes between CA-ABMR and TCMR. The overexpressed genes were annotated to NK cells and T cells in CA-ABMR and TCMR, and to neutrophils and monocytes in active-ABMR. The NK cell cytotoxicity and allograft rejection pathways were enriched in CA-ABMR. Genes encoding perforin, granzymes, and death receptor were overexpressed in CA-ABMR versus active-ABMR but not compared to TCMR. NK cell cytotoxicity pathway gene set variation analysis score was higher in CA-ABMR compared to active-ABMR but not in TCMR. Principal component analysis of the deconvolved immune cellular transcriptomes separated CA-ABMR and TCMR from active-ABMR and NR. Immunohistochemistry of kidney allograft biopsies validated a higher proportion of CD56+ NK cells in CA-ABMR than in active-ABMR. Thus, CA-ABMR was exemplified by the overexpression of the NK cell cytotoxicity pathway gene set and, surprisingly, molecularly more like TCMR than active-ABMR.

Prevalence and Associations of Cognitive Impairment in Adult Patients with Moyamoya Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Cognitive impairment, and in the long term Alzheimer's disease, vascular, or mixed dementia, are potential complications of moyamoya disease (MMD), of which the prevalence and associations are not well established. OBJECTIVE: We performed a systematic review and meta-analysis to investigate the prevalence of cognitive impairment in adult patients with MMD as well as its clinical and demographic correlates. METHODS: We performed a systematic search of four electronic databases: PubMed (MEDLINE), EMBASE, Scopus, and Cochrane Library, profiling studies from inception until 7 May 2023. Clinical data consisting of population characteristics, comorbidities, cognitive assessment tools used, and prevalence of cognitive impairment was extracted. RESULTS: Seventeen studies were included in the meta-analysis, with a total study population of 1,190 patients. All studies assessed cognition, and the overall prevalence of cognitive impairment in MMD patients was 54.59%. A subgroup analysis identified that the prevalence of executive dysfunction in MMD patients was 31.55%. We performed a meta-regression analysis which identified that cognitive impairment was not associated with age, education level, or a history of ischemic or hemorrhagic stroke. CONCLUSIONS: A substantial proportion of MMD patients have cognitive impairment, and cognitive impairment was found to have no association with a history of stroke. Further research is necessary to investigate the longitudinal relationship of MMD and cognitive impairment, and the impact of bypass surgery on cognitive impairment.

Postoperative Closed-Suction Drain in Anterior Orbitotomy.

Purpose To evaluate the role of a closed-suction drain in orbital mass excision following anterior orbitotomy. Methods This is a prospective, randomized comparative study of consecutive patients undergoing anterior orbitotomy and mass excision enrolled into two groups: group A (with drain) and group B (without drain). Clinical data included visual acuity assessment, proptosis measured by exophthalmometry, pain score assessment, eyelid swelling, and ocular motility. Postoperative data were compared for one to five days and at 14 and 30-day follow-ups in the two groups to evaluate the efficacy of closed-suction drain in orbital mass excision. Results Twenty-five patients planned for anterior orbitotomy were divided into two groups: group A (drain, n = 12) and group B (without drain, n = 13). The subsidence of proptosis (p = 0.041), eyelid swelling (p = 0.04), and restoration of ocular motility (p = 0.04) were faster in the drain group as compared to the non-drain group, which was observed as statistically significant. The outcomes at 30 days were comparable in both groups and none of the patients developed any long-term complications. Conclusion The use of orbital drains aids early postoperative recovery with faster subsidence of proptosis and eyelid edema, and rapid recovery of ocular movements but does not affect the final outcome. Orbital surgeons can individualize the use of closed-suction drains after anterior orbitotomy in cases with expected postoperative edema.

Combat ocular trauma in counterinsurgency operations.

PURPOSE: To identify the pattern, distribution, and causes of ocular injuries among the security personnel participating in counterinsurgency operations (CIOps). METHODS: This was a multicentric, retrospective review of chart records of patients reporting to three hospitals located in the geographic region affected by CIOps. The hospital registry was examined for all patients diagnosed with any type of ocular trauma between January 1, 2016, and December 31, 2019. A standardized proforma was filled out using the case records, and entries were validated. RESULTS: A total of 131 ocular injuries fulfilled the criteria of the study. The mean age of the patients was 32.46 ± 10.2 years. All the patients were males. The causes of the injuries were explosive blasts in 60 eyes (45.80%), gunshot wounds in 15 eyes (11.42%), stone pelting in 16 eyes (12.21%), training-related causes in 26 eyes (29.84%), vehicular accidents in 13 eyes (9.92%), and battery blast in one eye (0.76%). Among the type of injuries, open globe injuries included 66 eyes (50.38%), closed globe injuries included 35 eyes (26.72%), isolated lid lacerations included 14 eyes (10.68%), and isolated chemical injury was seen in two eyes (1.52%). Optic nerve head avulsion was seen in two eyes (1.52%). CONCLUSION: The study revealed a considerable number of ocular injuries related to combat, with explosive bursts being the leading cause. The incidence of ocular injuries was found to be highest in zone 1. This study emphasizes the importance of the need for soldiers deployed in active CIOps regions to wear protective eyewear, such as ballistic goggles or military combat eye protection, to reduce the risk of ocular injuries.

Clinical characteristics and outcomes of patients with post-stroke epilepsy: protocol for an individual patient data meta-analysis from the International Post-stroke Epilepsy Research Repository (IPSERR).

INTRODUCTION: Despite significant advances in managing acute stroke and reducing stroke mortality, preventing complications like post-stroke epilepsy (PSE) has seen limited progress. PSE research has been scattered worldwide with varying methodologies and data reporting. To address this, we established the International Post-stroke Epilepsy Research Consortium (IPSERC) to integrate global PSE research efforts. This protocol outlines an individual patient data meta-analysis (IPD-MA) to determine outcomes in patients with post-stroke seizures (PSS) and develop/validate PSE prediction models, comparing them with existing models. This protocol informs about creating the International Post-stroke Epilepsy Research Repository (IPSERR) to support future collaborative research. METHODS AND ANALYSIS: We utilised a comprehensive search strategy and searched MEDLINE, Embase, PsycInfo, Cochrane, and Web of Science databases until 30 January 2023. We extracted observational studies of stroke patients aged ≥18 years, presenting early or late PSS with data on patient outcome measures, and conducted the risk of bias assessment. We did not apply any restriction based on the date or language of publication. We will invite these study authors and the IPSERC collaborators to contribute IPD to IPSERR. We will review the IPD lodged within IPSERR to identify patients who developed epileptic seizures and those who did not. We will merge the IPD files of individual data and standardise the variables where possible for consistency. We will conduct an IPD-MA to estimate the prognostic value of clinical characteristics in predicting PSE. ETHICS AND DISSEMINATION: Ethics approval is not required for this study. The results will be published in peer-reviewed journals. This study will contribute to IPSERR, which will be available to researchers for future PSE research projects. It will also serve as a platform to anchor future clinical trials. TRIAL REGISTRATION NUMBER: NCT06108102.

Propensity-score matched analysis of patent foramen ovale closure in real-world study cohort with cryptogenic ischemic stroke.

INTRODUCTION: Patent foramen ovale (PFO) occurs in 25% of the general population and in 40% of cryptogenic ischemic stroke patients. Recent trials support PFO closure in selected patients with cryptogenic stroke. We examined the outcomes of transcatheter PFO closure in a real-world study cohort with cryptogenic stroke. METHODS: Consecutive ischemic stroke patients who were classified as cryptogenic on the TOAST aetiology and diagnosed with a PFO were included. All patients underwent either transcatheter PFO closure or medical therapy. A 2:1 propensity score matching by sex and Risk-of-Paradoxical-Embolism (RoPE) score was performed. Multivariable regression models adjusted for sex and RoPE score. RESULTS: Our cohort comprised 232 patients with mean age 44.3 years (SD 10.8) and median follow-up 1486.5 days. 33.2% were female. PFO closure (n=84) and medical therapy (n=148) groups were well-matched with <10% mean-difference in sex and RoPE score. Two patients in the treated group (2.4%) and seven in the control group (4.7%) had a recurrent ischemic stroke event. Multivariable Cox regression demonstrated a hazard-ratio of 0.26 (95%CI 0.03-2.13, P=0.21) for PFO closure compared to control. The incidence of atrial fibrillation (AF) detected post-PFO closure was similar between the treated and control (1.19% vs 1.35%, multivariable logistic regression odds-ratio 0.90, 95%CI 0.04-9.81, P=0.94). There were no major periprocedural complications documented. The difference in restricted mean survival-time free from stroke at two years between treated and control was 26.2 days (95%CI 5.52-46.85, P=0.013). CONCLUSIONS: In this Asian cohort, we report a low incidence of ischemic stroke recurrence and new-onset AF in patients who underwent PFO closure. When compared to the medical therapy group, there was no significant difference in the incidence of stroke recurrence and new-onset AF. Further studies involving larger real-world cohorts are warranted to identify patients who are more likely to benefit from PFO closure.

Ischemic and hemorrhagic strokes in young adults: Comparison of functional outcomes and return to work after stroke.

BACKGROUND: Functional recovery and return to work (RTW) after stroke are important rehabilitation goals that have significant impact on quality of life. Comparisons of functional outcomes and RTW between ischemic stroke (IS) and hemorrhagic stroke (HS), especially among young adults with stroke, have either been limited or yielded inconsistent results. We aimed to assess functional outcomes and ability to RTW in young adults with IS and HS, specifically primary spontaneous intracranial hemorrhage (SICH). METHODS: Young adults with IS or SICH aged 18-50-years-old were included. Outcome measures were modified Rankins score (mRS) on discharge and 3-months and RTW at 3-months after stroke. Good functional outcome was defined as an mRS of 0-2. RESULTS: We included 459 patients (71.5% male) with a mean age of 43.3 ± 5.7 years, comprising 49.2% IS and 50.8% SICH. Patients with SICH were more likely to have unfavourable shifts in ordinal mRS on discharge (OR 7.52, CI 5.18-10.87, p < 0.001) and at 3-months (OR 6.41, CI 4.17-9.80, p < 0.001). Patients with IS more likely achieved good functional outcomes (80.2% vs. 51.8%, p < 0.001) and were able to RTW at 3-months (54.4% vs. 36.3%, p = 0.004). Among all stroke patients with good functional outcomes, one-third did not RTW at 3-months. Patients with longer length of hospitalisation and higher National Institutes of Health Stroke Scale (NIHSS) score on admission, especially in the domain categories of level of consciousness, vision, motor function, language and neglect, were less likely to RTW at 3-months. CONCLUSION: Patients with IS were more likely to RTW when compared to SICH patients. Many young stroke patients did not RTW despite good functional outcomes. Further research should therefore address differences in prognosis and identify predictors that influence ability to RTW after stroke in the young adult population.