The challenge of unprecedented floods and droughts in risk management.

Risk management has reduced vulnerability to floods and droughts globally1,2, yet their impacts are still increasing3. An improved understanding of the causes of changing impacts is therefore needed, but has been hampered by a lack of empirical data4,5. On the basis of a global dataset of 45 pairs of events that occurred within the same area, we show that risk management generally reduces the impacts of floods and droughts but faces difficulties in reducing the impacts of unprecedented events of a magnitude not previously experienced. If the second event was much more hazardous than the first, its impact was almost always higher. This is because management was not designed to deal with such extreme events: for example, they exceeded the design levels of levees and reservoirs. In two success stories, the impact of the second, more hazardous, event was lower, as a result of improved risk management governance and high investment in integrated management. The observed difficulty of managing unprecedented events is alarming, given that more extreme hydrological events are projected owing to climate change3.

Future of Endovascular and Surgical Treatments of Atherosclerotic Intracranial Stenosis.

Intracranial atherosclerotic disease and resultant intracranial stenosis is a global leading cause of stroke, and poses an ongoing treatment challenge. Among patients with intracranial stenosis, those with hemodynamic compromise are at high risk for recurrent stroke despite medical therapy and risk factor modification. Revascularization of the hypoperfused territory is the most plausible treatment strategy for these high-risk patients, yet surgical and endovascular therapies have not yet shown to be sufficiently safe and effective in randomized controlled trials. Advances in diagnostic and therapeutic technologies have led to a resurgence of interest in surgical and endovascular treatment strategies, with a growing body of evidence to support their further evaluation in the treatment of select patient populations. This review outlines the current and emerging endovascular and surgical treatments and highlights promising future management strategies.

Salivary, lacrimal and nasal (SALANS) measure to assess side effects following radioactive iodine treatment: development, psychometric properties, and factor structure.

PURPOSE: This study aimed to develop and psychometrically evaluate a patient-reported outcome measure (PROM), SAlivary, LAcrimal, NaSal (SALANS), to document patients' symptoms after radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC). METHODS: We generated and iteratively revised SALANS items based on expert input, focus group discussions and feedback from cognitive testing (n = 17). We administered an initial SALANS measure with 39 items to patients diagnosed with DTC in the past two years (n = 105). Exploratory factor analysis (EFA) examined the factor structure of the SALANS items. We assessed the consistency reliability and related the total and subscale scores of the final SALANS to existing PROMs to assess validity. RESULTS: The final SALANS consisted of 33 items and six subscales (sialadenitis, taste, xerostomia, dry eyes, epiphora, and nasal) with six factors extracted by EFA. The six subscales demonstrated good internal reliability (α range = 0.87-0.92). The SALANS total score showed good convergent validity with the Xerostomia Inventory (r = 0.86) and good discriminant validity with a measure of spirituality (r = - 0.05). The mean SALANS total score was significantly higher (d = 0.5, p < 0.04) among patients who had RAI compared to those who did not have RAI. CONCLUSION: Preliminary evidence suggests that SALANS is a novel and reliable PROM to assess the type and frequency all symptoms experienced after RAI treatment for DTC. Future work is needed to further validate and develop the scale.

Changes in blood serum parameters in farmed rainbow trout (Oncorhynchus mykiss) during a piscine lactococcosis outbreak.

The aquaculture sector plays a vital role in global food security, yet it grapples with significant challenges posed by infectious diseases. Piscine lactococcosis is one of the significant threats in rainbow trout aquaculture due to its potential to cause severe economic losses through mortalities, reduced growth rates, and increased susceptibility to other pathogens. It poses challenges in disease management strategies, impacting the sustainability and profitability of rainbow trout farming. The current study focuses on the variations in serum blood parameters of farmed rainbow trout Oncorhynchus mykiss during a lactococcosis outbreak caused by Lactococcus garvieae. Blood samples were collected for biochemical analysis, fish were examined for parasites and bacteria, and DNA from bacterial colonies was PCR-amplified and sequenced for identification. Overall, 13 biochemical parameters, including proteins, enzymes, lipids, chemicals, and minerals, were measured in serum blood samples from both diseased and healthy fish. The results indicate significant alterations in the levels of these parameters during the outbreak, highlighting the impact of infections on the blood profile of farmed rainbow trout. Urea levels were significantly higher in diseased fish compared to controls, and creatinine, phosphorus, and magnesium also showed similar trends. Alanine aminotransferase and total protein levels were higher in control fish. Chloride levels differed significantly between groups. Iron levels were higher in controls and lower in diseased fish. No significant differences were found in other parameters. This study reveals significant changes in serum blood parameters of rainbow trout during a lactococcosis outbreak caused by L. garvieae. These changes highlight the potential of these parameters as tools for monitoring health status, stress, and aquaculture management. Continuous monitoring can provide valuable insights into disease severity and overall fish health, aiding in the development of improved management practices. The presented data contribute to understanding the pathophysiology of piscine lactococcosis and developing effective mitigation strategies for farmed rainbow trout.

GPR Mapping of Cavities in Complex Scenarios with a Combined Time-Depth Conversion.

The paper deals with a combined time-depth conversion strategy able to improve the reconstruction of voids embedded in an opaque medium, such as cavities, caves, empty hypogeal rooms, and similar targets. The combined time-depth conversion accounts for the propagation velocity of the electromagnetic waves both in free space and in the embedding medium, and it allows better imaging and interpretation of the underground scenario. To assess the strategy's effectiveness, ground penetrating radar (GPR) data referred to as an experimental test in controlled conditions are accounted for and processed by two different approaches to achieve focused images of the scenario under test. The first approach is based on a classical migration algorithm, while the second one faces the imaging as a linear inverse scattering approach. The results corroborate that the combined time-depth conversion improves the imaging in both cases.

Functional Intraregional and Interregional Heterogeneity between Myenteric Glial Cells of the Colon and Duodenum in Mice.

Enteric glia are a unique population of peripheral neuroglia that regulate homeostasis in the enteric nervous system (ENS) and intestinal functions. Despite existing in functionally diverse regions of the gastrointestinal tract, enteric glia have been approached scientifically as a homogeneous group of cells. This assumption is at odds with the functional specializations of gastrointestinal organs and recent data suggesting glial heterogeneity in the brain and ENS. Here, we used calcium imaging in transgenic mice of both sexes expressing genetically encoded calcium sensors in enteric glia and conducted contractility studies to investigate functional diversity among myenteric glia in two functionally distinct intestinal organs: the duodenum and the colon. Our data show that myenteric glia exhibit regionally distinct responses to neuromodulators that require intercellular communication with neurons to differing extents in the duodenum and colon. Glia regulate intestinal contractility in a region-specific and pathway-specific manner, which suggests regionally diverse engagement of enteric glia in local motor patterns through discrete signaling pathways. Further, functional response profiles delineate four unique subpopulations among myenteric glia that are differentially distributed between the colon and duodenum. Our findings support the conclusion that myenteric glia exhibit both intraregional and interregional heterogeneity that contributes to region-specific mechanisms that regulate digestive functions. Glial heterogeneity adds an unexpected layer of complexity in peripheral neurocircuits, and understanding the specific functions of specialized glial subtypes will provide new insight into ENS physiology and pathophysiology.SIGNIFICANCE STATEMENT Enteric glia modulate gastrointestinal functions through intercellular communication with enteric neurons. Whether heterogeneity exists among neuron-glia interactions in the digestive tract is not understood. Here, we show that myenteric glia display regional heterogeneity in their responses to neuromodulators in the duodenum and the colon, which are functionally distinct organs. Glial-mediated control of intestinal motility is region and pathway specific. Four myenteric glial subtypes are present within a given gut region that are differently distributed between gut regions. These data provide functional and regional insights into enteric circuit specificity in the adult enteric nervous system.

Outcomes in diabetic patients treated with SGLT2-Inhibitors with acute myocardial infarction undergoing PCI: The SGLT2-I AMI PROTECT Registry.

AIMS: To investigate in-hospital and long-term prognosis in T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-I versus other oral anti-diabetic agents (non-SGLT2-I users). METHODS: In this multicenter international registry all consecutive diabetic AMI patients undergoing percutaneous coronary intervention between 2018 and 2021 were enrolled and, based on the admission anti-diabetic therapy, divided into SGLT-I users versus non-SGLT2-I users. The primary endpoint was defined as a composite of cardiovascular death, recurrent AMI, and hospitalization for HF (MACE). Secondary outcomes included i) in-hospital cardiovascular death, recurrent AMI, occurrence of arrhythmias, and contrast-induced acute kidney injury (CI-AKI); ii) long-term cardiovascular mortality, recurrent AMI, heart failure (HF) hospitalization. RESULTS: The study population consisted of 646 AMI patients (with or without ST-segment elevation): 111 SGLT2-I users and 535 non-SGLT-I users. The use of SGLT2-I was associated with a significantly lower in-hospital cardiovascular death, arrhythmic burden, and occurrence of CI-AKI (all p < 0.05). During a median follow-up of 24 ± 13 months, the primary composite endpoint, as well as cardiovascular mortality and HF hospitalization were lower for SGLT2-I users compared to non-SGLT2-I patients (p < 0.04 for all). After adjusting for confounding factors, the use of SGLT2-I was identified as independent predictor of reduced MACE occurrence (HR=0.57; 95%CI:0.33-0.99; p = 0.039) and HF hospitalization (HR=0.46; 95%CI:0.21-0.98; p = 0.041). CONCLUSIONS: In T2DM AMI patients, the use of SGLT2-I was associated with a lower risk of adverse cardiovascular outcomes during index hospitalization and long-term follow-up. Our findings provide new insights into the cardioprotective effects of SGLT2-I in the setting of AMI. REGISTRATION: Data are part of the observational international registry: SGLT2-I AMI PROTECT. CLINICALTRIALS: gov Identifier: NCT05261867.

How we do it: the Zurich Microsurgery Lab technique for placenta preparation.

BACKGROUND: Perfused placentas provide an excellent and accessible model for microvascular dissection, microsuturing and microanastomosis training - particularly in the early microsurgical learning curve. This way, a significant amount of live animals can be spared. METHOD: We present the Zurich Microsurgery Lab protocol, detailing steps for obtaining, selecting, cleaning, flushing, cannulating, and preserving human placentas - as well as microsurgical training examples - in a tried-and-true, safe, cost-effective, and high-yield fashion. CONCLUSION: Our technique enables highly realistic microsurgical training (microdissection, microvascular repair, microanastomosis) based on readily available materials. Proper handling, preparation, and preservation of the perfused placenta models is key.

Adaptive Response in Rat Retinal Cell Cultures Irradiated with γ-rays.

Retina can receive incidental γ-ray exposure from various sources. For example, although radiation therapy is a crucial tool for managing head and neck tumors, patients may develop ocular complications as collateral damage from accidental irradiation. Recently, there has been concern that retinal irradiation during space flight may compromise mission goals and long-term quality of life after space travel. Previously, in our in vitro model, we proved that immature retinal cells are more vulnerable to γ-radiation than differentiated neurons. Here, we investigate if a low-dose pre-irradiation (0.025 Gy), known to have a protective effect in various contexts, can affect DNA damage and oxidative stress in cells exposed to a high dose of γ-rays (2 Gy). Our results reveal that pre-irradiation reduces 2 Gy effects in apoptotic cell number, H2AX phosphorylation and oxidative stress. These defensive effects are also evident in glial cells (reduction in GFAP and ED1 levels) and antioxidant enzymes (catalase and CuZnSOD). Overall, our results confirm that rat retinal cultures can be an exciting tool to study γ-irradiation toxic effects on retinal tissue and speculate that low irradiation may enhance the skill of retinal cells to reduce damage induced by higher doses.

Effectiveness of Flattening-Filter-Free versus Flattened Beams in V79 and Glioblastoma Patient-Derived Stem-like Cells.

Literature data on the administration of conventional high-dose beams with (FF) or without flattening filters (FFF) show conflicting results on biological effects at the cellular level. To contribute to this field, we irradiated V79 Chinese hamster lung fibroblasts and two patient-derived glioblastoma stem-like cell lines (GSCs-named #1 and #83) using a clinical 10 MV accelerator with FF (at 4 Gy/min) and FFF (at two dose rates 4 and 24 Gy/min). Cell killing and DNA damage induction, determined using the γ-H2AX assay, and gene expression were studied. No significant differences in the early survival of V79 cells were observed as a function of dose rates and FF or FFF beams, while a trend of reduction in late survival was observed at the highest dose rate with the FFF beam. GSCs showed similar survival levels as a function of dose rates, both delivered in the FFF regimen. The amount of DNA damage measured for both dose rates after 2 h was much higher in line #1 than in line #83, with statistically significant differences between the two dose rates only in line #83. The gene expression analysis of the two GSC lines indicates gene signatures mimicking the prognosis of glioblastoma (GBM) patients derived from a public database. Overall, the results support the current use of FFF and highlight the possibility of identifying patients with candidate gene signatures that could benefit from irradiation with FFF beams at a high dose rate.

S100B Affects Gut Microbiota Biodiversity.

This in vivo study in mice addresses the relationship between the biodiversity of the microbiota and the levels of S100B, a protein present in enteroglial cells, but also in foods such as milk. A positive significant correlation was observed between S100B levels and Shannon values, which was reduced after treatment with Pentamidine, an inhibitor of S100B function, indicating that the correlation was influenced by the modulation of S100B activity. Using the bootstrap average method based on the distribution of the S100B concentration, three groups were identified, exhibiting a significant difference between the microbial profiles. Operational taxonomic units, when analyzed by SIMPER analysis, showed that genera regarded to be eubiotic were mainly concentrated in the intermediate group, while genera potentially harboring pathobionts often appeared to be more concentrated in groups where the S100B amounts were very low or high. Finally, in a pilot experiment, S100B was administered orally, and the microbial profiles appeared to be modified accordingly. These data may open novel perspectives involving the possibility of S100B-mediated regulation in the intestinal microbiota.

Intrarectal Administration of Adelmidrol plus Hyaluronic Acid Gel Ameliorates Experimental Colitis in Mice and Inhibits Pro-Inflammatory Response in Ex Vivo Cultured Biopsies Derived from Ulcerative Colitis-Affected Patients.

Improving clinical outcomes and delaying disease recrudescence in Ulcerative Colitis (UC) patients is crucial for clinicians. In addition to traditional and new pharmacological therapies that utilize biological drugs, the development of medical devices that can ameliorate UC and facilitate the remission phase should not be overlooked. Drug-based therapy requires time to be personalized and to evaluate the benefit/risk ratio. However, the increasing number of diagnosed UC cases worldwide necessitates the exploration of new strategies to enhance clinical outcomes. By incorporating medical devices alongside pharmacological treatments, clinicians can provide additional support to UC patients, potentially improving their condition and slowing down the recurrence of symptoms. Chemically identified as an azelaic acid derivative and palmitoylethanolamide (PEA) analog, adelmidrol is a potent anti-inflammatory and antioxidant compound. In this study, we aimed to evaluate the effect of an intrarectal administration of 2% adelmidrol (Ade) and 0.1% hyaluronic acid (HA) gel formulation in both the acute and resolution phase of a mouse model of colitis induced via DNBS enema. We also investigated its activity in cultured human colon biopsies isolated from UC patients in the remission phase at follow-up when exposed in vitro to a cytomix challenge. Simultaneously, with its capacity to effectively alleviate chronic painful inflammatory cystitis when administered intravesically to urological patients such as Vessilen, the intrarectal administration of Ade/HA gel has shown remarkable potential in improving the course of colitis. This treatment approach has demonstrated a reduction in the histological damage score and an increase in the expression of ZO-1 and occludin tight junctions in both in vivo studies and human specimens. By acting independently on endogenous PEA levels and without any noticeable systemic absorption, the effectiveness of Ade/HA gel is reliant on a local antioxidant mechanism that functions as a "barrier effect" in the inflamed gut. Building on the findings of this preliminary study, we are confident that the Ade/HA gel medical device holds promise as a valuable adjunct in supporting traditional anti-UC therapies.

Mesenchymal Stem Cells in Soft Tissue Regenerative Medicine: A Comprehensive Review.

Soft tissue regeneration holds significant promise for addressing various clinical challenges, ranging from craniofacial and oral tissue defects to blood vessels, muscle, and fibrous tissue regeneration. Mesenchymal stem cells (MSCs) have emerged as a promising tool in regenerative medicine due to their unique characteristics and potential to differentiate into multiple cell lineages. This comprehensive review explores the role of MSCs in different aspects of soft tissue regeneration, including their application in craniofacial and oral soft tissue regeneration, nerve regeneration, blood vessel regeneration, muscle regeneration, and fibrous tissue regeneration. By examining the latest research findings and clinical advancements, this article aims to provide insights into the current state of MSC-based therapies in soft tissue regenerative medicine.

Trends in Literature on Cerebral Bypass Surgery: A Systematic Review.

INTRODUCTION: Ever since the beginning of cerebral bypass surgery, the role of the bypass has been debated and indications have changed over the last 5 decades. This systematic literature research analysed all clinical studies on cerebral bypass that have been published from January 1959 to January 2020 for their year of publication, country of origin, citation index, role of and indication for bypass, bypass technique, revascularized territory, flow capacity, and title (for word cloud analysis per decade). METHODS: A systematic literature research was conducted using PubMed, Web of Science, EMBASE, and SCOPUS databases. All studies that have been published until January 1, 2020, were included. RESULTS: Of 6,013 identified studies, 2,585 were included in the analysis. Of these, n = 1,734 (67%) studies addressed flow-augmentation bypass and n = 701 (27%) addressed flow-preservation bypass. The most common indication reported for flow augmentation is moyamoya (n = 877, 51%), followed by atherosclerotic steno-occlusive disease (n = 753, 43%). For flow preservation, the most common indication is studies reporting on cerebral aneurysm surgery (n = 659, 94%). The increasing popularity of reporting on these bypass operations almost came to an end with the FDA approval of flow diverters for aneurysm treatment in 2011. Japan is the country with the most bypass studies (cumulatively published 933 articles), followed by the USA (630 articles) and China (232 articles). DISCUSSION/CONCLUSION: Clinical studies on cerebral bypass surgery have become increasingly popular in the past decades. Since the introduction of moyamoya as a distinct pathologic entity, Asian countries in particular have a very active community regarding this disease, with an increasing number of articles published every year. Studies on bypass for chronic steno-occlusive disease peaked in the 1980s but have remained the main focus of bypass research, particularly in many European departments. The number of reports published on these bypass operations significantly decreased after the FDA approval of flow diverters for aneurysm treatment in 2011.

Machine Learning and Intracranial Aneurysms: From Detection to Outcome Prediction.

Machine learning (ML) is a rapidly rising research tool in biomedical sciences whose applications include segmentation, classification, disease detection, and outcome prediction. With respect to traditional statistical methods, ML algorithms have the potential to learn and improve their predictive performance when fed with large data sets without the need of being specifically programmed. In recent years, this technology has been increasingly applied for tackling clinical issues in intracranial aneurysm (IA) research. Several studies attempted to provide reliable models for enhanced aneurysm detection. Convolutional neural networks trained with variable degrees of human interaction on data from diverse imaging modalities showed high sensitivity in aneurysm detection tasks, also outperforming expert image analysis. Algorithms were also shown to differentiate ruptured from unruptured IAs, with however limited clinical relevance. For prediction of rupture and stability assessment, ML was preliminarily shown to achieve better performance compared to conventional statistical methods and existing risk scores. ML-based complication and functional outcome prediction in the event of SAH have been more extensively reported, in contrast with periprocedural outcome investigation in unruptured IA patients. ML has the potential to be a game changer in IA patient management. Currently clinical translation of experimental results is limited.

First report of totally robotically assisted hybrid coronary artery revascularization combining RE-MIDCAB and R-PCI: Case report.

A 62-year-old man presents to the Cardiology Department with a history of angina on exertion. Invasive coronary angiography revealed a severe three vessels coronary artery disease. The "Hybrid Heart Team" successfully performed a fully robotically assisted hybrid revascularization combining robotically enhanced-minimally invasive direct coronary artery bypass on the left anterior descending (LAD) and robotically assisted percutaneous coronary intervention on non-LAD lesions.

Segmentation techniques of brain arteriovenous malformations for 3D visualization: a systematic review.

BACKGROUND: Visualization, analysis and characterization of the angioarchitecture of a brain arteriovenous malformation (bAVM) present crucial steps for understanding and management of these complex lesions. Three-dimensional (3D) segmentation and 3D visualization of bAVMs play hereby a significant role. We performed a systematic review regarding currently available 3D segmentation and visualization techniques for bAVMs. METHODS: PubMed, Embase and Google Scholar were searched to identify studies reporting 3D segmentation techniques applied to bAVM characterization. Category of input scan, segmentation (automatic, semiautomatic, manual), time needed for segmentation and 3D visualization techniques were noted. RESULTS: Thirty-three studies were included. Thirteen (39%) used MRI as baseline imaging modality, 9 used DSA (27%), and 7 used CT (21%). Segmentation through automatic algorithms was used in 20 (61%), semiautomatic segmentation in 6 (18%), and manual segmentation in 7 (21%) studies. Median automatic segmentation time was 10 min (IQR 33), semiautomatic 25 min (IQR 73). Manual segmentation time was reported in only one study, with the mean of 5-10 min. Thirty-two (97%) studies used screens to visualize the 3D segmentations outcomes and 1 (3%) study utilized a heads-up display (HUD). Integration with mixed reality was used in 4 studies (12%). CONCLUSIONS: A golden standard for 3D visualization of bAVMs does not exist. This review describes a tendency over time to base segmentation on algorithms trained with machine learning. Unsupervised fuzzy-based algorithms thereby stand out as potential preferred strategy. Continued efforts will be necessary to improve algorithms, integrate complete hemodynamic assessment and find innovative tools for tridimensional visualization.

Reduced Environmental Dose Rates Are Responsible for the Increased Susceptibility to Radiation-Induced DNA Damage in Larval Neuroblasts of Drosophila Grown inside the LNGS Underground Laboratory.

A large amount of evidence from radiobiology studies carried out in Deep Underground Laboratories support the view that environmental radiation may trigger biological mechanisms that enable both simple and complex organisms to cope with genotoxic stress. In line with this, here we show that the reduced radiation background of the LNGS underground laboratory renders Drosophila neuroblasts more sensitive to ionizing radiation-induced (but not to spontaneous) DNA breaks compared to fruit flies kept at the external reference laboratory. Interestingly, we demonstrate that the ionizing radiation sensitivity of flies kept at the LNGS underground laboratory is rescued by increasing the underground gamma dose rate to levels comparable to the low-LET reference one. This finding provides the first direct evidence that the modulation of the DNA damage response in a complex multicellular organism is indeed dependent on the environmental dose rate.

Next-Generation Probiotics for Inflammatory Bowel Disease.

Engineered probiotics represent a cutting-edge therapy in intestinal inflammatory disease (IBD). Genetically modified bacteria have provided a new strategy to release therapeutically operative molecules in the intestine and have grown into promising new therapies for IBD. Current IBD treatments, such as corticosteroids and immunosuppressants, are associated with relevant side effects and a significant proportion of patients are dependent on these therapies, thus exposing them to the risk of relevant long-term side effects. Discovering new and effective therapeutic strategies is a worldwide goal in this research field and engineered probiotics could potentially provide a viable solution. This review aims at describing the proceeding of bacterial engineering and how genetically modified probiotics may represent a promising new biotechnological approach in IBD treatment.

Increased Ipsilateral Posterior Cerebral Artery P2-Segment Flow Velocity Predicts Hemodynamic Impairment.

BACKGROUND AND PURPOSE: Increased Transcranial Doppler flow velocity in the ipsilateral P2-segment of the posterior cerebral artery (PCA-P2: cm/second) is associated with recurrent cerebrovascular events in patients with unilateral internal carotid artery occlusion. However, its predictive value and correlation with hemodynamic impairment in an overall stroke patient cohort remains to be determined. METHODS: Transcranial doppler PCA-P2 flow velocity was measured in 88 patients with symptomatic unilateral steno-occlusive disease who also underwent blood oxygenation-level dependent cerebrovascular reactivity imaging (blood oxygenation-level dependent [BOLD]-cerebrovascular reactivity [CVR]). A multivariate linear regression was used to evaluate the independent correlation between the ipsilateral PCA-P2 flow velocity measurements and hemispheric BOLD-CVR. Follow-up BOLD-CVR imaging data, available in 25 patients, were used to evaluate the temporal evolution of the BOLD-CVR and PCA-P2 flow velocity association using a mixed-effect model. Furthermore, a transcranial doppler cutoff for hemodynamic failure stage 2 was determined. RESULTS: The ipsilateral systolic PCA-P2 flow velocity strongly correlated with hemispheric BOLD-CVR (R=0.79; R2=0.61), which remained unchanged when evaluating the follow-up data. Using a PCA-P2 systolic flow velocity cutoff value of 85 cm/second, patients with BOLD-CVR based hemodynamic failure stage 2 were diagnosed with an area under the curve of 95. CONCLUSIONS: In patients with symptomatic unilateral steno-occlusive disease, increased ipsilateral transcranial doppler PCA-P2 systolic flow velocity independently correlates with BOLD-CVR based hemodynamic failure. A cutoff value of 85 cm/second appears to indicate hemodynamic failure stage 2, but this finding needs to be validated in an independent patient cohort.