Secondary Infarction Research Articles

Long-term all-cause mortality of metabolic-dysfunction associated steatotic liver disease based on body weight phenotypes following acute myocardial infarction: A retrospective cohort study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity increases risk of cardiovascular disease. This cohort study examines the prognostic value of MASLD, across body weight categories, in a secondary preventative acute myocardial infarction (AMI) cohort. Patients with AMI were stratified into four phenotypes-obesity MASLD, non-obesity MASLD, obesity non-MASLD, non-obesity non-MASLD. The primary outcome was all-cause mortality. Cox regression analysis was performed to investigate determinants of long-term all-cause mortality. Of 5702 patients, majority were in the non-obesity non-MASLD group (66.7%), followed by obesity MASLD (16.1%), non-obesity MASLD (11.2%) and non-obesity MASLD (6.0%). Across the four phenotypes, obesity MASLD had the highest cardiometabolic burden, followed by non-obesity MASLD. Non-obesity MASLD had the highest risk of heart failure (p = 0.034), cardiogenic shock (p < 0.001), and all-cause long-term mortality (p = 0.019). The non-obesity MASLD (HR 1.400, 95%CI 1.077-1.820, p = 0.012) and obesity MASLD phenotypes (HR 1.222, 95%CI 1.005-1.485, p = 0.044) were independently associated with long-term all-cause mortality. Obesity and non-obesity MASLD phenotypes were predictors of all-cause mortality following AMI, with an even larger magnitude of mortality risk in the non-obesity MASLD group. The recognition of MASLD and its body weight phenotypes will be beneficial in the prognostication following AMI.

Implications of a new clinical classification of acute myocardial infarction

Abstract Background The Universal Definition of Myocardial Infarction has provided standardisation of the diagnostic criteria for myocardial infarction. However, there remain significant challenges in adopting some of the current recommendations in practice. The diagnostic criteria for type 2 myocardial infarction identify a heterogenous group of patients with variable clinical outcomes and no clear treatment implications to date. Purpose To determine the implications of a new clinical classification for myocardial infarction with more objective diagnostic criteria using cardiac imaging.(1) Methods In a prospective cohort study,(2) patients with type 2 myocardial infarction underwent coronary angiography and cardiac magnetic resonance imaging or echocardiography. The new classification was applied to identify (a) spontaneous myocardial infarction due to acute coronary pathology, (b) secondary myocardial infarction precipitated by acute illness in the presence of obstructive coronary artery disease, a new regional wall motion abnormality or infarct pattern scarring, and (c) no myocardial infarction in the absence of obstructive disease or new myocardial abnormality. The diagnostic outcome was the proportion of patients with type 2 myocardial infarction reclassified as having spontaneous, secondary or no myocardial infarction by the new clinical classification. The prognostic outcome was a composite of all-cause death, any recurrent myocardial infarction, or heart failure hospitalisation during follow up. Results In 100 patients (65 years, 43% women) with type 2 myocardial infarction, the new classification identified 25 and 31 patients with spontaneous and secondary myocardial infarction, respectively, and 44 without myocardial infarction (Figure 1). Compared to patients without myocardial infarction, those with secondary myocardial infarction were older, had more risk factors, and higher troponin concentrations (P&amp;lt;0.05 for all). In patients who underwent cardiac magnetic resonance imaging, there was evidence of infarct-pattern late gadolinium enhancement in 95% (19/20) and 60% (15/25) of patients with spontaneous and secondary myocardial infarction, respectively, which was more likely to be transmural in the former. In patients reclassified as secondary myocardial infarction, just 45% and 58% were established on aspirin or a lipid lowering therapy. During a median follow up of 4.4 years, death, myocardial infarction or heart failure hospitalization was more common in secondary myocardial infarction compared to those without myocardial infarction (55% [17/31] versus 16% [7/44], P&amp;lt;0.001; Figure 2). Conclusions A new clinical classification of myocardial infarction informed by cardiac imaging would reduce the diagnosis of myocardial infarction in acute illness and identify those patients at highest risk who are most likely to benefit from treatment.Figure 1:Alluvial plotFigure 2:Kaplan Meier curve

Sex differences in secondary prevention and outcomes post-myocardial infarction in Scotland

Abstract Background Sex differences in outcomes after myocardial infarction (MI) are of increasing interest. Differential receipt of evidence-based treatments may contribute to such disparities. Purpose In this study, we investigate sex differences in the burden of risk factors, in-hospital and long-term treatment and outcomes in contemporary practice in Scotland, by analysing a nationwide sample of consecutive MI admissions. Methods All MI admissions centrally recorded between 2010-2016 by Public Health Scotland were included and followed up until the end of 2021. Poisson regressions analysed in-hospital outcomes (percutaneous coronary intervention (PCI), mortality and post-discharge secondary prevention medication). Models were adjusted for age, co-morbidities and ST-elevation on the electrocardiogram. Royston-Parmar models analysed long-term outcomes (all-cause and cardiovascular mortality, major adverse cardiovascular events (MACE)) and were sequentially adjusted for confounders (age, comorbidities, secondary prevention medications). A 2:1 age and sex-matched general population were included as controls. Results Of a total 47,063 MI patients, 15,776 (33.5%) were women. They were matched with 81,641 controls free of major cardiovascular disease. Median (interquartile range) age was 64 (56-72) years for men and 69 (60-75) years for women. Obesity, hypertension and renal disease were the risk factors more prevalent amongst women, while men had higher rates of previous MI, peripheral vascular disease and atrial fibrillation. Compared to men, women were less likely to undergo PCI (risk ratio (95% confidence interval) – 0.87 (0.86-0.89)) or receive secondary prevention (0.94 (0.93-0.95)), but had similar in-hospital mortality (1.06 (0.99-1.13)), after multi-variable adjustment. Over a median follow-up of 8.4 (6.8-10.2) years, women had higher raw rates of adverse outcomes. However, after full confounder adjustment, this translated into lower risk for women of all cause-mortality 0.92 (0.89-0.95), cardiovascular mortality 0.82 (0.78-0.87) and MACE 0.92 (0.88-0.95) (Figure 1). The female survival advantage was attenuated post-MI in comparison to controls free of significant cardiovascular disease (Figure 2). Conclusions Women and men have different MI risk factor profiles. Women had overall worse crude outcome rates after MI, driven by age and comorbidities. This may have been driven further by undertreatment after MI, including PCI and secondary prevention. Urgent identification of drivers for such disparities in care is warranted in order to improve outcomes and ensure health equity.

Role of clipping in aneurysmal subarachnoid hemorrhage: a post hoc analysis of the Earlydrain trial

The choice between clipping and coiling of ruptured cerebral aneurysms in subarachnoid hemorrhage (SAH) remains controversial. The recently published Earlydrain trial provides the opportunity to analyze the latest clip-to-coil ratio in German-speaking countries and to evaluate vasospasm incidence and explorative outcome measures in both treatment modalities. We performed a post hoc analysis of the Earlydrain trial, a multicenter randomized controlled trial investigating the use of an additional lumbar drain in aneurysmal SAH. The decision whether to clip or to coil the ruptured aneurysm was left to the discretion of the participating centers, providing a real-world insight into current aneurysm treatment strategies. Earlydrain was performed in 19 centers in Germany, Switzerland, and Canada, recruiting 287 patients with aneurysmal SAH of all severity grades. Of these, 140 patients (49%) received clipping and 147 patients (51%) coiling. Age and clinical severity based on Hunt-Hess/WFNS grades and radiological criteria were similar. Clipping was more frequently used for anterior circulation aneurysms (55%), whereas posterior circulation aneurysms were mostly coiled (86%, p < 0.001). In high-volume recruiting centers, 56% of patients were treated with clipping, compared to 38% in other centers. A per-year analysis showed a stable and balanced clipping/coiling ratio over time. Regarding vasospasm, 60% of clipped versus 43% of coiled patients showed elevated transcranial Doppler criteria (p = 0.007), reflected in angiographic vasospasm rates (51% vs. 38%, p = 0.03). In contrast to the Earlydrain main results establishing the superiority of an additional lumbar drain, explorative outcomes after clipping and coiling measured by secondary infarctions, mortality, modified Rankin Score, Glasgow Outcome Scale Extended, or Barthel-Index showed no significant differences after discharge and at six months. In clinical practice, aneurysm clipping is still a frequently used method in aneurysmal SAH. Apart from a higher rate of vasospasm in the clipping group, an exploratory outcome analysis showed no difference between the two treatment methods. Further development of periprocedural treatment modalities for clipped ruptured aneurysms to reduce vasospasm is warranted.

Duration of spreading depression is the electrophysiological correlate of infarct growth in malignant hemispheric stroke.

Spreading depolarizations (SD) contribute to lesion progression after experimental focal cerebral ischemia while such correlation has never been shown in stroke patients. In this prospective, diagnostic study, we investigate the association of SDs and secondary infarct progression after malignant hemispheric stroke. SDs were continuously monitored for 3-9 days with electrocorticography after decompressive hemicraniectomy for malignant hemispheric stroke. To ensure valid detection and analysis of SDs, a threshold based on the electrocorticographic baseline activity was calculated to identify valid electrocorticographic recordings. Subsequently SD characteristics were analyzed in association to infarct progression based on serial MRI. Overall, 62 patients with a mean stroke volume of 289.6 ± 68 cm3 were included. Valid electrocorticographic recordings were found in 44/62 patients with a mean recording duration of 139.6 ± 26.5 hours and 52.5 ± 39.5 SDs per patient. Infarct progression of more than 5% was found in 21/44 patients. While the number of SDs was similar between patients with and without infarct progression, the SD-induced depression duration per day was significantly longer in patients with infarct progression (593.8 vs. 314.1 minutes; *p = 0.046). Therefore, infarct progression is associated with a prolonged SD-induced depression duration. Real-time analysis of electrocorticographic recordings may identify secondary stroke progression and help implementing targeted management strategies.

Association of Fluid Balance and Hemoglobin Decline With Neurological Outcome After Aneurysmal Subarachnoid Hemorrhage.

To explore the relationship between fluid balance and hemoglobin decline with secondary infarctions and neurologic outcome in aneurysmal subarachnoid hemorrhage (aSAH) patients. Secondary analysis of the Earlydrain trial, a prospective randomized controlled study investigating prophylactic lumbar drain use in aSAH patients. Patients with aSAH treated in ICUs at 19 tertiary hospitals in Germany, Switzerland, and Canada. From January 2011 to January 2016, 287 patients were enrolled in the Earlydrain trial. Only files with complete information on both daily hemoglobin and balance values were used, leaving 237 patients for analysis. Investigation of fluid balance management and hemoglobin levels during the initial 8 days post-aSAH to establish thresholds for unfavorable outcomes and assess their impact on secondary infarctions and 6-month neurologic outcome on the modified Rankin Scale (mRS). Patients with unfavorable outcome after 6 months (mRS > 2) showed greater hemoglobin decline and increased cumulative fluid balance. A significant inverse relationship existed between fluid balance and hemoglobin decline. Thresholds for unfavorable outcome were 10.4 g/dL hemoglobin and 4894 mL cumulative fluid balance in the first 8 days. In multivariable analysis, fluid balance, but not fluid intake, remained significantly associated with unfavorable outcome, while the influence of hemoglobin lessened. Fluid balance but not hemoglobin related to secondary infarctions, with the effect being significant after inverse probability of treatment weighting. Transfusion was associated with unfavorable outcomes. Increased fluid balance influences hemoglobin decline through hemodilution. Fluid overload, rather than a slight decrease in hemoglobin levels, appears to be the primary factor contributing to poor outcomes in aSAH patients. The results suggest aiming for euvolemia and that a modest hemoglobin decline may be tolerated. It may be advisable to adopt a restrictive approach to transfusions, as they can potentially have a negative effect on outcome.

Ketamine-induced prevention of SD-associated late infarct progression in experimental ischemia

Spreading depolarizations (SDs) occur frequently in patients with malignant hemispheric stroke. In animal-based experiments, SDs have been shown to cause secondary neuronal damage and infarct expansion during the initial period of infarct progression. In contrast, the influence of SDs during the delayed period is not well characterized yet. Here, we analyzed the impact of SDs in the delayed phase after cerebral ischemia and the potential protective effect of ketamine. Focal ischemia was induced by distal occlusion of the left middle cerebral artery in C57BL6/J mice. 24 h after occlusion, SDs were measured using electrocorticography and laser-speckle imaging in three different study groups: control group without SD induction, SD induction with potassium chloride, and SD induction with potassium chloride and ketamine administration. Infarct progression was evaluated by sequential MRI scans. 24 h after occlusion, we observed spontaneous SDs with a rate of 0.33 SDs/hour which increased during potassium chloride application (3.37 SDs/hour). The analysis of the neurovascular coupling revealed prolonged hypoemic and hyperemic responses in this group. Stroke volume increased even 24 h after stroke onset in the SD-group. Ketamine treatment caused a lesser pronounced hypoemic response and prevented infarct growth in the delayed phase after experimental ischemia. Induction of SDs with potassium chloride was significantly associated with stroke progression even 24 h after stroke onset. Therefore, SD might be a significant contributor to delayed stroke progression. Ketamine might be a possible drug to prevent SD-induced delayed stroke progression.

Analysis of Cerebral Spinal Fluid Drainage and Intracranial Pressure Peaks in Patients with Subarachnoid Hemorrhage

BackgroundAfter aneurysmal subarachnoid hemorrhage (aSAH), elevated intracranial pressure (ICP) due to disrupted cerebrospinal fluid (CSF) dynamics is a critical concern. An external ventricular drainage (EVD) is commonly employed for management; however, optimal strategies remain debated. The randomized controlled Earlydrain trial showed that an additional prophylactic lumbar drainage (LD) after aneurysm treatment improves neurological outcome. We performed a post hoc investigation on the impact of drainage volumes and critical ICP values on patient outcomes after aSAH.MethodsUsing raw patient data from Earlydrain, we analyzed CSF drainage amounts and ICP measurements in the first 8 days after aSAH. Outcomes were the occurrence of secondary infarctions and the score on the modified Rankin scale after 6 months, dichotomized in values of 0–2 as favorable and 3–6 as unfavorable. Repeated measurements were considered with generalized estimation equations.ResultsEarlydrain recruited 287 patients, of whom 221 received an EVD and 140 received an LD. Higher EVD volumes showed a trend to more secondary infarctions (p = 0.09), whereas higher LD volumes were associated with less secondary infarctions (p = 0.009). The mean total CSF drainage was 1052 ± 659 mL and did not differ concerning infarction and neurological outcome. Maximum ICP values were higher in patients with poor outcomes but not related to drainage volumes via EVD. After adjustment for aSAH severity and total CSF drainage, higher LD volume was linked to favorable outcome (per 100 mL: odds ratio 0.61 (95% confidence interval 0.39–0.95), p = 0.03), whereas higher EVD amounts were associated with unfavorable outcome (per 100 mL: odds ratio 1.63 (95% confidence interval 1.05–2.54), p = 0.03).ConclusionsFindings indicate that effects of CSF drainage via EVD and LD differ. Higher amounts and higher proportions of LD volumes were associated with better outcomes, suggesting a potential quantity-dependent protective effect. Optimizing LD volume and mitigating ICP spikes may be a strategy to improve patient outcomes after aSAH.Clinical trial registration: ClinicalTrials.gov identifier: NCT01258257.

OxyHbMeter-a novel bedside medical device for monitoring cell-free hemoglobin in the cerebrospinal fluid-proof of principle.

Delayed cerebral ischemia (DCI) occurs in up to one third of patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). Untreated, it leads to secondary cerebral infarctions and is frequently associated with death or severe disability. After aneurysm rupture, erythrocytes in the subarachnoid space lyse and liberate free hemoglobin (Hb), a key driver for the development of DCI. Hemoglobin in the cerebrospinal fluid (CSF-Hb) can be analyzed through a two-step procedure of centrifugation to exclude intact erythrocytes and subsequent spectrophotometric quantification. This analysis can only be done in specialized laboratories but not at the bedside in the intensive care unit. This limits the number of tests done, increases the variability of the results and restricts accuracy. Bedside measurements of CSF-Hb as a biomarker with a point of care diagnostic test system would allow for a continuous monitoring for the risk of DCI in the individual patient. In this study, a microfluidic chip was explored that allows to continuously separate blood particles from CSF or plasma based on acoustophoresis. An in vitro test bench was developed to test in-line measurements with the developed microfluidic chip and a spectrometer. The proof of principle for a continuous particle separation device has been established with diluted blood and CSF samples from animals and aSAH patients, respectively. Processing 1 mL of blood in our microfluidic device was achieved within around 70 min demonstrating only minor deviations from the gold standard centrifugation (7% average error of patient samples), while saving several hours of processing time and additionally the reduction of deviations in the results due to manual labor.

Early Complications and Outcome After Treatment of Ruptured Aneurysms in Patients with Subarachnoid Hemorrhage–A Post Hoc Analysis of the EARLYDRAIN Trial

Aneurysmal subarachnoid hemorrhage (aSAH) from a ruptured intracranial aneurysm is a severe, life-threatening condition, with high morbidity and mortality. The current treatment often involves surgical clipping or endovascular treatment within the first 24-48 hours. Although there is ample evidence of complications in treating unruptured aneurysms, similar data in patients with acutely ruptured aneurysms are limited. The recently completed EARLYDRAIN trial showed improved neurologic results from lumbar drainage after aneurysm treatment in patients with aSAH. Using this data set, we aim to study the frequency and effects of complications and identify associated risk factors. A substudy was carried out of the prospective multicenter randomized controlled EARLYDRAIN trial. We analyzed treatment-associated complications (bleeding and/or infarctions) detected on computed tomography on day 1 after aneurysm occlusion. Outcomes were the occurrence of postprocedural complications, secondary infarctions in the acute phase, and the modified Rankin Scale score after 6 months. The EARLYDRAIN trial recruited 287 patients in 19 centers. Of these patients, 56 (19.5%) experienced a treatment complication. Twenty-five patients (8.7%) experienced postprocedural intracranial hemorrhage and 34 patients (11.8%) experienced a treatment-associated infarction. Patients with a complication showed more secondary infarctions (P= 0.049) and worse neurologic outcomes after 180 days (P= 0.025) compared with patients with no complication. Aneurysm location, rebleeding before the treatment, number of patients recruited per center, and the day of the treatment were independent risk factors for the occurrence of complications. The present study shows that patients with aSAH frequently experience intervention-associated complications associated with aneurysm occlusion required to prevent recurrent hemorrhage. Consequently, patients with aSAH with treatment-related complications more often experience a worse clinical course and poor outcome.

Risk factors of pulmonary cavitation in COVID-19 pneumonia

To identify the risk factors of pulmonary cavitation in COVID-19 pneumonia. A retrospective study included 8261 patients with COVID-19 between April 2020 and March 2022. Inclusion criteria: age >18 years, COVID-19 confirmed by polymerase chain reaction. Two cohorts of patients were formed: 40 patients with pulmonary cavitation and 40 patients without these lesions. Both groups were comparable in age, lung lesion volume and oxygenation. Sex, age, length of hospital-stay, CT grade of lung lesion, comorbidities, treatment, respiratory support, oxygen saturation and in-hospital outcomes were evaluated. The highest lung lesion volume during hospitalization was assessed. CT was performed upon admission and approximately every 5 days for evaluation of treatment. Statistical analysis was performed using the IBM SPSS Statistics software (IBM Corporation, USA). Patients with pulmonary cavitation significantly differed in age, SpO2, lung lesion volume, more common non-invasive ventilation and prolonged hospital-stay. Cardiovascular diseases were more common in both groups. Univariate logistic regression analysis revealed age, cardiovascular diseases, CT-based severity of lung damage, absence of biological therapy and non-invasive ventilation as risk factors of pulmonary cavitation. According to multivariate logistic regression analysis, these predictors were CT-based severity of lung damage and absence of biological therapy. Univariate logistic regression analysis showed that pulmonary cavitation had no significant effect on mortality (OR=2.613, 95% CI: 0.732-9.322, p=0.139). The risk of pulmonary cavitation in COVID-19 is directly related to advanced lung damage and untimely or absent biological therapy with IL-6 inhibitors. Pulmonary cavitation in COVID-19 is not a typical manifestation of disease and can be caused by some factors: fungal infection, secondary bacterial infection, tuberculosis and pulmonary infarction. Further study of this problem is required to develop diagnostic algorithms and treatment tactics.

Innovative prognostication: a novel nomogram for post-interventional aneurysmal subarachnoid hemorrhage patients.

Spontaneous aneurysmal subarachnoid hemorrhage (aSAH) is a common acute cerebrovascular disease characterized by severe illness, high mortality, and potential cognitive and motor impairments. We carried out a retrospective study at Fujian Provincial Hospital to establish and validate a model for forecasting functional outcomes at 6 months in aSAH patients who underwent interventional embolization. 386 aSAH patients who underwent interventional embolization between May 2012 and April 2022 were included in the study. We established a logistic regression model based on independent risk factors associated with 6-month adverse outcomes (modified Rankin Scale Score ≥ 3, mRS). We evaluated the model's performance based on its discrimination, calibration, clinical applicability, and generalization ability. Finally, the study-derived prediction model was also compared with other aSAH prognostic scales and the model's itself constituent variables to assess their respective predictive efficacy. The predictors considered in our study were age, the World Federation of Neurosurgical Societies (WFNS) grade of IV-V, mFisher score of 3-4, secondary cerebral infarction, and first leukocyte counts on admission. Our model demonstrated excellent discrimination in both the modeling and validation cohorts, with an area under the curve of 0.914 (p < 0.001, 95%CI = 0.873-0.956) and 0.947 (p < 0.001, 95%CI = 0.907-0.987), respectively. Additionally, the model also exhibited good calibration (Hosmer-Lemeshow goodness-of-fit test: X2 = 9.176, p = 0.328). The clinical decision curve analysis and clinical impact curve showed favorable clinical applicability. In comparison to other prediction models and variables, our model displayed superior predictive performance. The new prediction nomogram has the capability to forecast the unfavorable outcomes at 6 months after intervention in patients with aSAH.

Development and validation of a new model for the early diagnosis of tuberculous meningitis in adults based on simple clinical and laboratory parameters

BackgroundThe differential diagnosis between tuberculous meningitis (TBM) and viral meningitis (VM) or bacterial meningitis (BM) remains challenging in clinical practice, particularly in resource-limited settings. This study aimed to establish a diagnostic model that can accurately and early distinguish TBM from both VM and BM in adults based on simple clinical and laboratory parameters.MethodsPatients diagnosed with TBM or non-TBM (VM or BM) between January 2012 and October 2021 were retrospectively enrolled from the General Hospital (derivation cohort) and Branch Hospital (validation cohort) of Ningxia Medical University. Demographic characteristics, clinical symptoms, concomitant diseases, and cerebrospinal fluid (CSF) parameters were collated. Univariable logistic analysis was performed in the derivation cohort to identify significant variables (P < 0.05). A multivariable logistic regression model was constructed using these variables. We verified the performance including discrimination, calibration, and applicability of the model in both derivation and validation cohorts.ResultsA total of 222 patients (70 TBM and 152 non-TBM [75 BM and 77 VM]) and 100 patients (32 TBM and 68 non-TBM [31 BM and 37 VM]) were enrolled as derivation and validation cohorts, respectively. The multivariable logistic regression model showed that disturbance of consciousness for > 5 days, weight loss > 5% of the original weight within 6 months, CSF lymphocyte ratio > 50%, CSF glucose concentration < 2.2 mmol/L, and secondary cerebral infarction were independently correlated with the diagnosis of TBM (P < 0.05). The nomogram model showed excellent discrimination (area under the curve 0.959 vs. 0.962) and great calibration (P-value in the Hosmer–Lemeshow test 0.128 vs. 0.863) in both derivation and validation cohorts. Clinical decision curve analysis showed that the model had good applicability in clinical practice and may benefit the entire population.ConclusionsThis multivariable diagnostic model may help clinicians in the early discrimination of TBM from VM and BM in adults based on simple clinical and laboratory parameters.

Perfusion Computed Tomography as a Screening Tool for Pending Delayed Cerebral Ischemia in Comatose Patients After Aneurysmal Subarachnoid Hemorrhage: A Retrospective Cohort Study

BackgroundAneurysmal subarachnoid hemorrhage (aSAH) is frequently complicated by delayed cerebral ischemia (DCI), leading to poor outcomes. Early diagnosis of DCI is crucial for improving survival and outcomes but remains challenging in comatose patients. In this study, we aimed to evaluate computed tomography with angiography and perfusion (P-CT) as a screening modality on postictal days four and eight for impending DCI after aSAH in comatose patients using vasospasm with hypoperfusion (hVS) as a surrogate and DCI-related infarction as an outcome measure. Two objectives were set: (1) to evaluate the screening’s ability to accurately risk stratify patients and (2) to assess the validity of P-CT screening.MethodsWe conducted a retrospective review of the records of comatose patients with aSAH from January 2019 to December 2021 who were monitored with P-CT scans on days four and eight. The event rates of DCI-related infarction, hVS, and endovascular rescue therapy (ERT) were analyzed, and the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for DCI were calculated. DCI-related infarction was defined as new secondary cerebral infarction > 48 h < 6 weeks post aSAH not attributable to other causes, and hVS was defined as arterial narrowing with corresponding hypoperfusion on P-CT.ResultsFifty-six comatose patients were included, and 98 P-CT scans were performed. The incidence of DCI-related infarction was 40%. Screening P-CT on days four and eight found vasospasm in 23% of all patients, including 11% with hVS. A positive hVS on day four or eight revealed a relative risk of 2.4 [95% confidence interval (CI) 1.13–5.11, p = 0.03], sensitivity of 23% (95% CI 8–45, p = 0.03), specificity of 95% (95% CI 36–100, p = 0.03), PPV of 0.83 (95% CI 0.36–1.00, p = 0.03), and NPV of 0.65 (95% CI 0.50–0.78). Six positive P-CT scans led to digital subtraction angiography in five patients, three of whom received ERT. All ERT-intervened patients developed DCI-related infarction.ConclusionsP-CT resulted in few interventions and often resulted in late detection of DCI at an irreversible stage. Although a positive P-CT result accurately predicts impending DCI-related infarction, screening on days four and eight alone in comatose patients with aSAH often fails to timely detect impending DCI. Based on our analysis, we cannot recommend P-CT as a screening modality. P-CT is likely best used as a confirmatory test prior to invasive interventions when guided by continuous multimodal monitoring; however, prospective studies with comparison groups are warranted. The need for a reliable continuous screening modality is evident because of the high rate of deterioration and narrow treatment window.

Retrospective study of spontaneous subarachnoid haemorrhage: vasospasm and other complications (Part III)

Background. Acute subarachnoid haemorrhage (SAH) is a dangerous condition: roughly 50% of patients die within 30 days, nearly 25% develop significant neuropsychological and cognitive deficits, about 10% suffer from other complications, and only around 15% recover fully. One of the main causes of mortality is cerebral vasospasm (CVS), a cause of delayed cerebral ischaemia (DCI), which can lead to secondary cerebral infarction. Thus, early detection of CVS is crucial for improving patient outcomes.The aim of this study was to analyse the demographic and clinical (including complications) data of patients diagnosed with SAH, to evaluate the diagnostic methods, and to investigate the prevalence and treatment of complications.Materials and methods. This retrospective study included 102 patients diagnosed with spontaneous SAH, aged at least 18 years, who were treated in the Vilnius University Hospital Santaros Klinikos (VUL SK) in 2014-2017. The obtained VUL SK data were selected by the I60 ICD-10-CM code and depersonalized. Head computerized tomography (CT), CT angiography (CTA), digital subtraction angiography (DSA), transcranial color-coded duplex sonography (TCCS), and magnetic resonance angiography (MRA) were used to evaluate the cerebral arteries.Results. In 102 patients (mean age 58±16 years; 55% female), the most common cause of spontaneous SAH was ruptured aneurysm, the most common arterial sites were the middle cerebral artery (36%), anterior cerebral artery and/or communicating artery (together 33%), and internal carotid artery (20%). In-hospital mortality was as high as 21%. All patients underwent head CT, 78% CTA, 33% DSA, 8% TCCS, and 1% MRA. 71% patients experienced SAH complications: 66% acute, 27% chronic. The most common acute complications were cerebral oedema (34%), rebleeding (29%), and acute ischaemia (23%), the most common chronic complications hydrocephalus (11%), DCI (9%), and CVS (8%).Conclusions. CVS was diagnosed considerably less frequently in this study compared to other studies. While the diagnosis rates of ischaemia and hyponatremia were likewise significantly lower in this study compared to those in others, they are in line with the CVS diagnosis rate. Aside from the CVS and CVS-related complications, all the other SAH complications were roughly within the range of the other studies.

Predictive value of whole-brain CT perfusion combined with ABCD3 score for short-term secondary cerebral infarction after TIA.

To investigate the predictive value of Whole Brain CT Perfusion (WB-CTP) combined with the ABCD3 score in patients with transient ischemic attack (TIA). A total of 336 TIA patients with TIA underwent WB-CTP and ABCD3 score assessment within 48 h of admission. Spearman correlation test was performed to analyze the relationship between the degree of vascular stenosis, relative perfusion values, and ABCD3 score. Logistic regression analysis was used to identify independent risk factors for secondary cerebral infarction. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of relative cerebral blood flow (rCBF), degree of vascular stenosis, ABCD3 score, and the WB-CTP-ABCD3 combined model for secondary cerebral infarction after TIA. Calibration curves and H-L tests were used to evaluate the predictive efficacy of the model. Among the 336 TIA patients, 143 showed abnormal perfusion areas and 146 had responsible vessel stenosis. The degree of vascular stenosis, relative time-to-maximum (rTmax), and relative mean transit time (rMTT) were positively correlated with the ABCD3 score, while rCBF and relative cerebral blood volume (rCBV) were negatively correlated with the ABCD3 score. ROC curve analysis identified a cutoff value of 0.8205 for rCBF, with a sensitivity of 84.10% and specificity of 58.10% for distinguishing the cerebral infarction group from the non-cerebral infarction group. Furthermore, rCBF ≤ 0.8205, degree of vascular stenosis, and ABCD3 score > 6 were identified as independent risk factors for secondary cerebral infarction in TIA patients within 90 days in TIA patients. The AUC of the WB-CTP-ABCD3 combined model for predicting secondary cerebral infarction within 90 days was 0.836. The model risk was assessed by plotting calibration curves. The value of p for the H-L goodness of fit test was 0.366 (p > 0.05), which indicated that the difference between the obtained model and the perfect model were statistically insignificant. The combined model of WB-CTP-ABCD3 shows promise as a valuable method for predicting secondary cerebral infarction within 90 days following TIA.

Effectiveness of Lumbar Cerebrospinal Fluid Drain Among Patients With Aneurysmal Subarachnoid Hemorrhage

After aneurysmal subarachnoid hemorrhage, the use of lumbar drains has been suggested to decrease the incidence of delayed cerebral ischemia and improve long-term outcome. To determine the effectiveness of early lumbar cerebrospinal fluid drainage added to standard of care in patients after aneurysmal subarachnoid hemorrhage. The EARLYDRAIN trial was a pragmatic, multicenter, parallel-group, open-label randomized clinical trial with blinded end point evaluation conducted at 19 centers in Germany, Switzerland, and Canada. The first patient entered January 31, 2011, and the last on January 24, 2016, after 307 randomizations. Follow-up was completed July 2016. Query and retrieval of data on missing items in the case report forms was completed in September 2020. A total of 20 randomizations were invalid, the main reason being lack of informed consent. No participants meeting all inclusion and exclusion criteria were excluded from the intention-to-treat analysis. Exclusion of patients was only performed in per-protocol sensitivity analysis. A total of 287 adult patients with acute aneurysmal subarachnoid hemorrhage of all clinical grades were analyzable. Aneurysm treatment with clipping or coiling was performed within 48 hours. A total of 144 patients were randomized to receive an additional lumbar drain after aneurysm treatment and 143 patients to standard of care only. Early lumbar drainage with 5 mL per hour was started within 72 hours of the subarachnoid hemorrhage. Primary outcome was the rate of unfavorable outcome, defined as modified Rankin Scale score of 3 to 6 (range, 0 to 6), obtained by masked assessors 6 months after hemorrhage. Of 287 included patients, 197 (68.6%) were female, and the median (IQR) age was 55 (48-63) years. Lumbar drainage started at a median (IQR) of day 2 (1-2) after aneurysmal subarachnoid hemorrhage. At 6 months, 47 patients (32.6%) in the lumbar drain group and 64 patients (44.8%) in the standard of care group had an unfavorable neurological outcome (risk ratio, 0.73; 95% CI, 0.52 to 0.98; absolute risk difference, -0.12; 95% CI, -0.23 to -0.01; P = .04). Patients treated with a lumbar drain had fewer secondary infarctions at discharge (41 patients [28.5%] vs 57 patients [39.9%]; risk ratio, 0.71; 95% CI, 0.49 to 0.99; absolute risk difference, -0.11; 95% CI, -0.22 to 0; P = .04). In this trial, prophylactic lumbar drainage after aneurysmal subarachnoid hemorrhage lessened the burden of secondary infarction and decreased the rate of unfavorable outcome at 6 months. These findings support the use of lumbar drains after aneurysmal subarachnoid hemorrhage. ClinicalTrials.gov Identifier: NCT01258257.

Repurposing the KCa3.1 Blocker Senicapoc for Ischemic Stroke

Senicapoc, a small molecule inhibitor of the calcium-activated potassium channel KCa3.1, was safe and well-tolerated in clinical trials for sickle cell anemia. We previously reported proof-of-concept data suggesting that both pharmacological inhibition and genetic deletion of KCa3.1 reduces infarction and improves neurologic recovery in rodents by attenuating neuroinflammation. Here we evaluated the potential of repurposing senicapoc for ischemic stroke. In cultured microglia, senicapoc inhibited KCa3.1 currents with an IC50 of 7 nM, reduced Ca2+ signaling induced by the purinergic agonist ATP, suppressed expression of pro-inflammatory cytokines and enzymes (iNOS and COX-2), and prevented induction of the inflammasome component NLRP3. When transient middle cerebral artery occlusion (tMCAO, 60 min) was induced in male C57BL/6 J mice, twice daily administration of senicapoc at 10 and 40 mg/kg starting 12 h after reperfusion dose-dependently reduced infarct area determined by T2-weighted magnetic resonance imaging (MRI) and improved neurological deficit on day 8. Ultra-high-performance liquid chromatography/mass spectrometry analysis of total and free brain concentrations demonstrated sufficient KCa3.1 target engagement. Senicapoc treatment significantly reduced microglia/macrophage and T cell infiltration and activation and attenuated neuronal death. A different treatment paradigm with senicapoc started at 3 h and MRI on day 3 and day 8 revealed that senicapoc reduces secondary infarct growth and suppresses expression of inflammation markers, including T cell cytokines in the brain. Lastly, we demonstrated that senicapoc does not impair the proteolytic activity of tissue plasminogen activator (tPA) in vitro. We suggest that senicapoc could be repurposed as an adjunctive immunocytoprotective agent for combination with reperfusion therapy for ischemic stroke.

Application of Myocardial Contrast-Enhanced Ultrasound in Heart Transplantation in Patients with Acute Myocardial Infarction：A Case Report

Background: MCE is a safe and effective myocardial perfusion assessment technique; it is used for the assessment of post MI viability. Case Presentation: A 52-year-old male with cardiogenic shock caused by secondary acute myocardial infarction and successful coronary stent implantation with ECMO, IABP and ventilator assistance and with no significant recovery of postoperative cardiac function. The result of MCE was also reported. The allograft was successfully performed 8 days after ECMO-assisted support. The patient was successfully transferred to the general ward 8 days after surgery and successfully discharged on day 86 of admission. Conclusions: ECMO provides effective mechanical assistance support for patients with end-stage heart failure, buys time for heart transplantation surgery, and was an effective cardiopulmonary support treatment. An evaluation of myocardial perfusion and survival quantity was an important reference for emergency heart transplantation.

Man With Left Flank Pain

An 81-year-old man with a peripheral vascular disease presented to the emergency department with acute left flank pain for several hours that resolved after oral analgesia. He was hemodynamically stable, and his abdomen and flank were soft and nontender. Laboratory tests included an acutely increased creatinine level of 1.5 mg/dL. A bedside ultrasound demonstrated a hyperechoic left kidney with perinephric fluid and an abdominal aortic aneurysm of 8 cm (Figure 1). Abdominal computed tomography demonstrated an abdominal aortic aneurysm with aorto-left retroaortic renal vein fistula and secondary renal vein infarction with decreased parenchemal enhancement and perinephric fluid (Figure 2).