The IJMS World Conference of Medical Student Research and an Overview of the IJMS Volume 10 Issue 2

We introduce the first IJMS World Conference of Medical Student Research as a unique opportunity for medical students and early-career scientists around the globe to share the results of their research in an online worldwide platform, aimed at increasing accessibility to research for medical students and creating bonds of collaborations between participants and future scientists and leaders of medical research education. This is also the second issue of the 10-year anniversary of the Journal, and we describe in summary the published research and experiences of this issue.&nbsp

Prediction of delayed reperfusion in patients with incomplete reperfusion following thrombectomy.

BACKGROUND The clinical course of patients with incomplete reperfusion after thrombectomy, defined as an expanded Thrombolysis in Cerebral Infarction (eTICI) score of 2a-2c, is heterogeneous. Patients showing delayed reperfusion (DR) have good clinical outcomes, almost comparable to patients with ad-hoc TICI3 reperfusion. We aimed to develop and internally validate a model that predicts DR occurrence in order to inform physicians about the likelihood of a benign natural disease progression. PATIENTS AND METHODS Single-center registry analysis including all consecutive, study-eligible patients admitted between 02/2015 and 12/2021. Preliminary variable selection for the prediction of DR was performed using bootstrapped stepwise backward logistic regression. Interval validation was performed with bootstrapping and the final model was developed using a random forests classification algorithm. Model performance metrics are reported with discrimination, calibration, and clinical decision curves. Primary outcome was concordance statistics as a measure of goodness of fit for the occurrence of DR. RESULTS A total of 477 patients (48.8% female, mean age 74 years) were included, of whom 279 (58.5%) showed DR on 24 follow-up. The model's discriminative ability for predicting DR was adequate (C-statistics 0.79 [95% CI: 0.72-0.85]). Variables with strongest association with DR were: atrial fibrillation (aOR 2.06 [95% CI: 1.23-3.49]), Intervention-To-Follow-Up time (aOR 1.06 [95% CI: 1.03-1.10]), eTICI score (aOR 3.49 [95% CI: 2.64-4.73]), and collateral status (aOR 1.33 [95% CI: 1.06-1.68]). At a risk threshold of R = 30%, use of the prediction model could potentially reduce the number of additional attempts in one out of four patients who will have spontaneous DR, without missing any patients who do not show spontaneous DR on follow-up. CONCLUSIONS The model presented here shows fair predictive accuracy for estimating chances of DR after incomplete thrombectomy. This may inform treating physicians on the chances of a favorable natural disease progression if no further reperfusion attempts are made

Association of Intravenous Thrombolysis with Delayed Reperfusion After Incomplete Mechanical Thrombectomy.

PURPOSE Treatment of distal vessel occlusions causing incomplete reperfusion after mechanical thrombectomy (MT) is debated. We hypothesized that pretreatment with intravenous thrombolysis (IVT) may facilitate delayed reperfusion (DR) of residual vessel occlusions causing incomplete reperfusion after MT. METHODS Retrospective analysis of patients with incomplete reperfusion after MT, defined as extended thrombolysis in cerebral infarction (eTICI) 2a-2c, and available perfusion follow-up imaging at 24 ± 12 h after MT. DR was defined as absence of any perfusion deficit on time-sensitive perfusion maps, indicating the absence of any residual occlusion. The association of IVT with the occurrence of DR was evaluated using a logistic regression analysis adjusted for confounders. Sensitivity analyses based on IVT timing (time between IVT start and the occurrence incomplete reperfusion following MT) were performed. RESULTS In 368 included patients (median age 73.7 years, 51.1% female), DR occurred in 225 (61.1%). Atrial fibrillation, higher eTICI grade, better collateral status and longer intervention-to-follow-up time were all associated with DR. IVT did not show an association with the occurrence of DR (aOR 0.80, 95% CI 0.44-1.46, even in time-sensitive strata, aOR 2.28 [95% CI 0.65-9.23] and aOR 1.53 [95% CI 0.52-4.73] for IVT to incomplete reperfusion following MT timing <80 and <100 min, respectively). CONCLUSION A DR occurred in 60% of patients with incomplete MT at ~24 h and did not seem to occur more often in patients receiving pretreatment IVT. Further research on potential associations of IVT and DR after MT is required

Bridging intravenous thrombolysis in patients with atrial fibrillation.

Background and purpose 40% of acute ischemic stroke patients treated by mechanical thrombectomy (MT) have a clinical history of atrial fibrillation (AF). The safety of bridging intravenous thrombolysis (IVT) (MT + IVT) is currently being discussed. We aimed to analyze the interaction between oral anticoagulation (OAC) status or AF with bridging IVT, regarding the occurrence of symptomatic intracranial hemorrhage (sICH) and functional outcome. Materials and Methods Multicentric observational cohort study (BEYOND-SWIFT registry) of consecutive patients undergoing MT between 2010 and 2018 (n = 2,941). Multinomial regression models were adjusted for prespecified baseline and plausible pathophysiological covariates identified on a univariate analysis to assess the association of AF and OAC status with sICH and good outcomes (90-day modified Rankin Scale score 0-2). Results In the total cohort (median age 74, 50.6% women), 1,347 (45.8%) patients had AF. Higher admission National Institutes of Health Stroke Scale (NIHSS) score (aOR 1.04 [95% 1.02-1.06], per point of increase) and prior medication with Vitamin K antagonists (VKA) (aOR 2.19 [95% 1.27-3.66]) were associated with sICH. Neither AF itself (aOR 0.71 [95% 0.41-1.24]) nor bridging IVT (aOR 1.08 [0.67-1.75]) were significantly associated with increased sICH. Receiving bridging IVT (aOR 1.61 [95% 1.24-2.11]) was associated with good 90-day outcome, with no interaction between AF and IVT (p = 0.92). Conclusion Bridging IVT appears to be a reasonable clinical option in selected patients with AF. Given the increased sICH risk in patients with VKA, subgroup analysis of the randomized controlled trials should analyze whether patients with VKA might benefit from withholding bridging IVT. Registration clinicaltrials.gov; Unique identifier: NCT03496064

Importance of Delayed Reperfusions in Patients With Incomplete Thrombectomy.

BACKGROUND There is paucity of data regarding the effects of delayed reperfusion (DR) on clinical outcomes in patients with incomplete reperfusion following mechanical thrombectomy. We hypothesized that DR has a strong association with clinical outcome in patients with incomplete reperfusion after mechanical thrombectomy (expanded Thrombolysis in Cerebral Infarction, 2a-2c). METHODS Single-institution's stroke registry retrospective analysis of patients admitted from February 2015 to December 2020. DR was defined as the absence of any perfusion delay on ≈24-hour contrast-enhanced follow-up perfusion imaging, whereas persistent perfusion deficit denotes a perfusion delay corresponding to the catheter angiographic deficit directly after the intervention. The association of perfusion outcome (DR versus persistent perfusion deficit) with the occurrence of new infarcts and 90-day functional independence (modified Rankin Scale score 0-2) was evaluated using logistic regression analyses. Comparison of predictive accuracy was evaluated by calculating area under the curve for models with and without perfusion outcome. RESULTS In 566 patients (mean age 74, 49.6% female), new infarcts in the incomplete reperfusion areas were less common in DR versus persistent perfusion deficit patients (small punctiform: 17.1% versus 25%, large confluent: 7.9% versus 63.2%; P=0.001). After adjustment for confounders, DR was a strong predictor of functional independence (adjusted odds ratio, 2.37 [95% CI 1.34-4.23]). There was a significant improvement in predictive accuracy of functional independence when perfusion outcome was added to expanded Thrombolysis in Cerebral Infarction alone (area under the curve 0.57 versus 0.62, P=0.01). CONCLUSIONS Occurrence of DR is closely associated with tissue outcome and functional independence. DR may be an independent prognostic parameter, suggesting it as a potential outcome surrogate for medical rescue therapies

Perceived acceptable uncertainty regarding comparability of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment.

BACKGROUND Most trials comparing endovascular treatment (EVT) alone versus intravenous thrombolysis with alteplase (IVT) + EVT in directly admitted patients with a stroke are non-inferiority trials. However, the margin based on the level of uncertainty regarding non-inferiority of the experimental treatment that clinicians are willing to accept to incorporate EVT alone into clinical practice remains unknown. OBJECTIVE To characterize what experienced stroke clinicians would consider an acceptable level of uncertainty for hypothetical decisions on whether to administer IVT or not before EVT in patients admitted directly to EVT-capable centers. METHODS A web-based, structured survey was distributed to a cross-section of 600 academic neurologists/neurointerventionalists. For this purpose, a response framework for a hypothetical trial comparing IVT+EVT (standard of care) with EVT alone (experimental arm) was designed. In this trial, a similar proportion of patients in each arm achieved functional independence at 90 days. Invited physicians were asked at what level of certainty they would feel comfortable skipping IVT in clinical practice, considering these hypothetical trial results. RESULTS There were 180 respondents (response rate: 30%) and 165 with complete answers. The median chosen acceptable uncertainty suggesting reasonable comparability between both treatments was an absolute difference in the rate of day 90 functional independence of 3% (mode 5%, IQR 1-5%), with higher chosen margins observed in interventionalists (aOR 2.20, 95% CI 1.06 to 4.67). CONCLUSION Physicians would generally feel comfortable skipping IVT before EVT at different certainty thresholds. Most physicians would treat with EVT alone if randomized trial data suggested that the number of patients achieving functional independence at 90 days was similar between the two groups, and one could be sufficiently sure that no more than 3 out of 100 patients would not achieve functional independence at 90 days due to skipping IVT

Physical health trajectories of young people commenced on clozapine

Objectives:Clozapine is the most effective antipsychotic medication, but it has the highest propensity for metabolic side effects. A clozapine clinic was established within an early intervention for psychosis service to facilitate the timely commencement of clozapine and to manage the associated adverse effects. This study describes the changes in the weight, body mass index (BMI), waist circumference and blood pressure after 6 months in young people commenced on clozapine.Method:This was a prospective cohort study of all young people, aged 15-24 years, commenced on clozapine within an early intervention service in Melbourne, Australia, between 01.04.2016 and 30.06.2018. Continuous data were analyzed with paired t-test and categorical with Wilcoxon signed-rank test.Results:Twenty-six young people received 6 months of treatment with clozapine, of whom the mean age was 19.8 years (s.d. ±3.1) and 66.7% were male. After 6 months, the mean weight gain was 5.1 kg (s.d. ±10.1 kg) and over half (53.8%) gained clinically significant weight. The proportion of young people classified as either overweight or obese rose from 69.2% to 88.5% (p = 0.006). The proportion of young people with a waist circumference above the recommended parameters increased from 57.9% to 78.9% (p = 0.008). Hypertension was present in 30%, and after 6 months, 45% had hypertension (p = 0.64). Metformin was prescribed to 34.6%, typically to those with the greatest and most rapid weight gain.Conclusion:Among young people with treatment resistant psychosis, clozapine is associated with significant metabolic side effects in the early stages of commencement. More interventions aimed at attenuating this weight gain are needed