A Future Blood Test to Detect Cerebral Aneurysms.

Intracranial aneurysms are reported to affect 2-5% of the population. Despite advances in the surgical management of this disease, diagnostic technologies have marginally improved and still rely on expensive or invasive imaging procedures. Currently, there is no blood-based test to detect cerebral aneurysm formation or quantify the risk of rupture. The aim of this review is to summarize current literature on the mechanism of aneurysm formation, specifically studies relating to inflammation, and provide a rationale and commentary on a hypothetical future blood-based test. Efforts should be focused on clinical-translational approaches to create an assay to screen for cerebral aneurysm presence and risk-stratify patients to allow for superior treatment timing and management. Cerebral Aneurysm Blood Test Considerations: There are multiple caveats to development of a putative blood test to detect cerebral aneurysm presence.

Pseudopeptosomes: non-lipidated vesicular assemblies from bispidine-appended pseudopeptides.

We report a novel molecular topology-based approach for creating reproducible vesicular assemblies in different solvent environments (including aqueous) using specifically designed pseudopeptides. Deviating from the classical "polar head group and hydrophobic tail" model of amphiphiles, we showed (reversible) self-assembly of synthesized pseudopeptides into vesicles. Naming these new type/class of vesicles "pseudopetosomes", we characterized them by high-resolution microscopy (scanning electron, transmission electron, atomic force, epifluorescence and confocal) along with dynamic light scattering. While accounting for hydropathy index of the constituent amino acids (side chains) of pseudopeptides, we probed molecular interactions, resulting in assembly of pseudopeptosomes by spectroscopy (fourier-transform infrared and fluorescence). Molecular characterization by X-ray crystallography and circular dichroism revealed "tryptophan (Trp)-Zip" arrangements and/or hydrogen-bonded one-dimensional assembly depending on specific pseudopeptides and solvent environments. Our data indicated that pseudopeptosomes are formed in solutions by self-assembly of bispidine pseudopeptides (of Trp, leucine and alanine amino-acid constituents) into sheets that transform into vesicular structures. Thus, we showed that assembly of pseudopeptosomes utilizes the full spectrum of all four weak interactions essential in biological systems. Our findings have direct implications in chemical and synthetic biology, but may also provide a new avenue of investigations on origins of life via pseudopeptosome-like assemblies. We also showed that these designer peptides can act as carriers for cellular transport.

Molecular dynamics simulation-based trinucleotide and tetranucleotide level structural and energy characterization of the functional units of genomic DNA.

Genomes of most organisms on earth are written in a universal language of life, made up of four units - adenine (A), thymine (T), guanine (G), and cytosine (C), and understanding the way they are put together has been a great challenge to date. Multiple efforts have been made to annotate this wonderfully engineered string of DNA using different methods but they lack a universal character. In this article, we have investigated the structural and energetic profiles of both prokaryotes and eukaryotes by considering two essential genomic sites, viz., the transcription start sites (TSS) and exon-intron boundaries. We have characterized these sites by mapping the structural and energy features of DNA obtained from molecular dynamics simulations, which considers all possible trinucleotide and tetranucleotide steps. For DNA, these physicochemical properties show distinct signatures at the TSS and intron-exon boundaries. Our results firmly convey the idea that DNA uses the same dialect for prokaryotes and eukaryotes and that it is worth going beyond sequence-level analyses to physicochemical space to determine the functional destiny of DNA sequences.

Interaction of admission platelet count with current medications and the risk for chronic subdural recurrence.

OBJECTIVE: Chronic subdural hematoma (cSDH) has a reported 10%-24% rate of recurrence after surgery, and prognostic models for recurrence have produced equivocal results. The objective of this study was to leverage a data mining algorithm, chi-square automatic interaction detection (CHAID), which can incorporate continuous, nominal, and binary data into a decision tree, to identify the most robust predictors of repeat surgery for cSDH patients. METHODS: This was a retrospective cohort study of all patients with SDH from two level 1 trauma centers at a single institution. All patients underwent cSDH evacuation performed by 15 neurosurgeons between 2011 and 2020. The primary outcome was the rate of repeat surgery for recurrent cSDH following the initial evacuation. The authors used CHAID to identify relevant predictors of repeat surgery, including age, sex, comorbidities, postsurgical complications, platelet count prior to the first procedure, midline shift prior to the first procedure, hematoma volume, and preoperative use of anticoagulants, antiplatelets, or statins. RESULTS: Sixty (13.8%) of 435 study-eligible patients (average age 74.0 years) had a cSDH recurrence. These patients had 2.0 times greater odds of having used anticoagulants. The final CHAID model had an overall accuracy of 87.4% and an area under the curve of 0.76. According to the model, the predictor with the strongest association with cSDH recurrence was admission platelet count. Approximately 26% of patients (n = 23/87) with an admission platelet count < 157 × 109/L had a cSDH recurrence, whereas none of the 44 patients with admission platelets > 313 × 109/L had a recurrence. Approximately 17% of patients in the 157-313 × 109/L platelet group who had used preoperative statins required a second procedure, which was associated with a 2.3 times increased risk for repeat surgery compared to those who had not used statins preoperatively. Among those who had not used preoperative statins, a platelet count ≤ 179 × 109/L on admission for the first procedure was the strongest differentiator for a second surgery (n = 5/22 [23%]), which increased the risk of recurrence by 4.5 times. Among the patients using preoperative statins, the use of anticoagulants was the strongest differentiator for requiring repeat surgery (n = 11/33 [33%]). CONCLUSIONS: The described model identified platelet count on admission as the most important predictor of repeat cSDH surgery, followed by preoperative statin use and anticoagulant use. Critical cutoffs for platelet count were identified, which future studies should evaluate to determine if they are modifiable or reflective of underlying disease states.

Arachnoid webs causing rostral syrinx due to ball-valve effect: an illustrative report of two cases.

An arachnoid web is a pathological formation of the arachnoid membrane. It is a rare phenomenon but is known to lead to syrinx formation in the spinal cord along with pain and neurological deficits. On imaging, the 'scalpel sign' is pathognomonic for an arachnoid web. The etiology of syrinx formation from an arachnoid web is currently unknown. This report documents the only two cases of arachnoid webs with an extensive syrinx in which a likely pathophysiologic mechanism is identified. Both cases presented with motor deficits. The patients had no history of trauma or infection. After extensive workup in both patients and observation of the scalpel sign an arachnoid web was suspected. In both cases, the patients were treated surgically after an arachnoid web was suspected. Intra-operative ultrasound visualized in both cases demonstrates a fenestration in the web that allowed passage of cerebrospinal fluid in a rostral-caudal direction due to a ball-valve effect.

A Three-Dimensional-Based Morphometric Analysis of a Standardized Overcorrection Technique for Fronto-Orbital Advancement in Metopic Craniosynostosis.

INTRODUCTION: The concept of "overcorrection" for trigonocephaly has been reported to achieve both anterior cranial fossa expansion and normalization of craniofacial form. The purpose of this study is to describe in detail a standardized technique to fronto-orbital advancement utilizing the concept of "overcorrection" and objectively evaluate intermediate results. METHODS: This retrospective study included patients with isolated metopic synostosis who underwent surgery via the proposed surgical technique and age and sex-matched unaffected controls. Craniofacial morphometric analysis was performed on pre-, immediate post-, and intermediate postoperative (>2 years) three-dimensional (3D)-rendered computed tomographic (CT) scans and photographs. Key CT-based measurements included interzygomaticofrontal suture distance (IZFS), endocranial bifrontal angle (ECA), and temporal expansion. 3D photogrammetry was performed using established measurements and associated Z-scores converted. A Paired t-test and analysis of variance were performed when appropriate. RESULTS: Forty-one patients were included. A comparison of pre- and immediate postoperative CT scans demonstrated statistically significant increases in all measurements. Subset analysis of 12 patients with intermediate follow-up (age: 39.6 ± 3.6 months) demonstrated significant differences from preoperative values except for IZFS, which decreased from immediate postoperative values and was smaller than age- and sex-matched controls. 3D photogrammetry demonstrated a mean Z-score above the norm for frontal breath. 3D photogrammetry is also positively correlated with CT-based measurements. CONCLUSIONS: This standardized "overcorrection" approach for trigonocephaly can provide the appropriate changes to maintain a normal ECA despite a reduction in bifrontal width over time. 3D photogrammetry positively correlated with CT-based measurements and may provide useful information when following patients clinically. Long-term follow-up assessment to determine the necessary degree of overcorrection at skeletal mature is needed.

The Clinical Significance of Clinocephaly in Late-Presentation Sagittal Craniosynostosis.

The diagnosis of late-presentation sagittal suture craniosynostosis (SCS) can be challenging, especially in the setting of subtle physical exam findings. The clinical significance of clinocephaly-a retro-coronal concavity along the midvault-in this context remains unknown. The aim of this study is to evaluate the predictive value of clinocephaly in identifying late-presentation SCS.A retrospective chart review of all patients >1 year old presenting to the craniofacial clinic with a concern for SCS was performed. The presence or absence of SCS in the setting of clinocephaly was recorded following diagnostic imaging. Student's t test, Chi Square test, and multivariate logistic regression analysis were performed to determine predictors for SCS.75 patients met inclusion criteria. 32 patients (42.7%, 6% female) were diagnosed with SCS. No difference in age between patients with and without SCS was detected. Stratification of patients by age (1-2, 2-4, and >4 years) revealed a higher rate of SCS in younger patients (P = 0.04). The cephalic index (C.I.) of those with sagittal synostosis was significantly smaller but within the normal range, indicating a more scaphocephalic shape (P = 0.003). Logistic regression analysis revealed that C.I. was a strong predictor for SCS (P = 0.003). Of those with SCS, a mix of complete and partial fusion of the sagittal suture was appreciated.This study found that 42.7% of patients with clinocephaly had SCS. C.I. was the only predictor for SCS and unique suture fusion patterns were identified in those with SCS. This study suggests that clinocephaly should be considered a core component of the exam and work-up for SCS. Future studies aimed at evaluating the positive predictive value of this exam finding and identifying risk factors associated with late-presentation SCS are underway.

Aspects of Biological Replication and Evolution Independent of the Central Dogma: Insights from Protein-Free Vesicular Transformations and Protein-Mediated Membrane Remodeling.

Biological membrane remodeling is central to living systems. In spite of serving as "containers" of whole-living systems and functioning as dynamic compartments within living systems, biological membranes still find a "blue collar" treatment compared to the "white collar" nucleic acids and proteins in biology. This may be attributable to the fact that scientific literature on biological membrane remodeling is only 50 years old compared to ~ 150 years of literature on proteins and a little less than 100 years on nucleic acids. However, recently, evidence for symbiotic origins of eukaryotic cells from data only on biological membranes was reported. This, coupled with appreciation of reproducible amphiphilic self-assemblies in aqueous environments (mimicking replication), has already initiated discussions on origins of life beyond nucleic acids and proteins. This work presents a comprehensive compilation and meta-analyses of data on self-assembly and vesicular transformations in biological membranes-starting from model membranes to establishment of Influenza Hemagglutinin-mediated membrane fusion as a prototypical remodeling system to a thorough comparison between enveloped mammalian viruses and cellular vesicles. We show that viral membrane fusion proteins, in addition to obeying "stoichiometry-driven protein folding", have tighter compositional constraints on their amino acid occurrences than general-structured proteins, regardless of type/class. From the perspective of vesicular assemblies and biological membrane remodeling (with and without proteins) we find that cellular vesicles are quite different from viruses. Finally, we propose that in addition to pre-existing thermodynamic frameworks, kinetic considerations in de novo formation of metastable membrane structures with available "third-party" constituents (including proteins) were not only crucial for origins of life but also continue to offer morphological replication and/or functional mechanisms in modern life forms, independent of the central dogma.

Computed tomography associated radiation exposure in children with craniosynostosis.

BACKGROUND: The role of computed tomography (CT) for diagnosis and surgical planning for craniosynostosis (CS) is well-established. The aim of this study was to quantify the cumulative medical radiation exposure from CT in patients with CS at a tertiary care children's hospital. METHODS: Medical records of patients who presented at < 2 years of age and underwent surgical intervention for CS were examined for demographic information. Effective radiation dose (ERD) in mSv was calculated for each head CT. Descriptive statistics and ANOVA were performed. Mean ± SD is reported; p < 0.05 was considered significant. RESULTS: Two hundred seventy-two patients met inclusion criteria: 241 nonsyndromic and 31 with syndromic diagnoses. For nonsyndromic patients, mean age at first head CT was 6.0 ± 4.9 months, mean number of CT scans obtained was 2.1 ± 1.1, and the mean total combined ERD was 9.1 ± 4.8 mSv. CT scans obtained at < 6 months of age had a significantly greater ERD than those obtained at > 6 months, 5.3 ± 1.9 versus 4.3 ± 1.4 mSv, respectively (p = 0.001). CONCLUSIONS: Patients with nonsyndromic CS undergo 2 CT scans on average related to their diagnosis, with a mean total ERD of 9.1 mSv; this is equivalent to 1.5 years of the average annual background radiation dose a person living in the USA will encounter from environmental radiation, medical exposures, and consumer products. A CT obtained at < 6 months is associated with a higher ERD; thus, we recommend delaying imaging from the initial presentation to the time of pre-operative planning when possible.

Quantification of pain in sickle mice using facial expressions and body measurements.

Pain is a hallmark feature of sickle cell disease (SCD). Subjects typically quantify pain by themselves, which can be biased by other factors leading to overtreatment or under-treatment. Reliable and accurate quantification of pain, in real time, might enable to provide appropriate levels of analgesic treatment. The mouse grimace scale (MGS), a standardized behavioral coding system with high accuracy and reliability has been used to quantify varied types of pain. We hypothesized that addition of the objective parameters of body length and back curvature will strengthen the reproducibility of MGS. We examined MGS scores and body length and back curvature of transgenic BERK sickle and control mice following cold treatment or following treatment with analgesic cannabinoid CP55,940. We observed that sickle mice demonstrated decreased length and increased back curvature in response to cold. These observations correlate with changes in facial expression for the MGS score. CP55,940 treatment of sickle mice showed an increase in body length and a decrease in back curvature concordant with MGS scores indicative of an analgesic effect. Thus, body parameters combined with facial expressions may provide a quantifiable unbiased method for objective measure of pain in SCD.

Evidence for the involvement of nematocidal toxins of Purpureocillium lilacinum 6029 cultured on Karanja deoiled cake liquid medium.

In present study, in vitro nematocidal bioassays, FT-IR and HPLC analysis were employed to demonstrate the involvement of toxins of Purpureocillium lilacinum in killing root-knot nematodes (Meloidogyne incognita). During growth study, maximum mycelial biomass (10.52 g/l) in de-oiled Karanja cake medium was achieved on 8th day while complete mortality of nematodes was obtained by 6th day filtrate (FKSM). Maximum production of crude nematocidal toxin was recorded on 7th day suggesting that the toxin production was paralleled with growth of the fungus. The median lethal concentration (LC50) determined for the crude toxin from 6th day to 10th day ranged from 89.41 to 43.21 ppm. The median lethal time (LT50) for the crude toxin of FKSM was found to be 1.46 h. This is the first report of implementing a comparative infra-red spectroscopy coupled with HPLC analysis to predict the presence of nematocidal toxin in the fungal filtrate cultured on Karanja deoiled cake liquid medium.

D2N: Distance to the native.

Root-mean-square-deviation (RMSD), of computationally-derived protein structures from experimentally determined structures, is a critical index to assessing protein-structure-prediction-algorithms (PSPAs). The development of PSPAs to obtain 0Å RMSD from native structures is considered central to computational biology. However, till date it has been quite challenging to measure how far a predicted protein structure is from its native - in the absence of a known experimental/native structure. In this work, we report the development of a metric "D2N" (distance to the native) - that predicts the "RMSD" of any structure without actually knowing the native structure. By combining physico-chemical properties and known universalities in spatial organization of soluble proteins to develop D2N, we demonstrate the ability to predict the distance of a proposed structure to within ±1.5Ǻ error with a remarkable average accuracy of 93.6% for structures below 5Ǻ from the native. We believe that this work opens up a completely new avenue towards assigning reliable structures to whole proteomes even in the absence of experimentally determined native structures. The D2N tool is freely available at http://www.scfbio-iitd.res.in/software/d2n.jsp.

Capturing native/native like structures with a physico-chemical metric (pcSM) in protein folding.

Specification of the three dimensional structure of a protein from its amino acid sequence, also called a "Grand Challenge" problem, has eluded a solution for over six decades. A modestly successful strategy has evolved over the last couple of decades based on development of scoring functions (e.g. mimicking free energy) that can capture native or native-like structures from an ensemble of decoys generated as plausible candidates for the native structure. A scoring function must be fast enough in discriminating the native from unfolded/misfolded structures, and requires validation on a large data set(s) to generate sufficient confidence in the score. Here we develop a scoring function called pcSM that detects true native structure in the top 5 with 93% accuracy from an ensemble of candidate structures. If we eliminate the native from ensemble of decoys then pcSM is able to capture near native structure (RMSD<=5Ǻ) in top 10 with 86% accuracy. The parameters considered in pcSM are a C-alpha Euclidean metric, secondary structural propensity, surface areas and an intramolecular energy function. pcSM has been tested on 415 systems consisting 142,698 decoys (public and CASP-largest reported hitherto in literature). The average rank for the native is 2.38, a significant improvement over that existing in literature. In-silico protein structure prediction requires robust scoring technique(s). Therefore, pcSM is easily amenable to integration into a successful protein structure prediction strategy. The tool is freely available at http://www.scfbio-iitd.res.in/software/pcsm.jsp.

Comparative genomic and proteomic analyses of PE/PPE multigene family of Mycobacterium tuberculosis H37Rv and H37Ra reveal novel and interesting differences with implications in virulence.

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading infectious disease taking one human life every 15 s globally. The two well-characterized strains H(37)Rv and H(37)Ra, derived from the same parental strain M. tuberculosis H(37), show dramatically different pathogenic phenotypes. PE/PPE gene family, comprising of 176 open reading frames and present exclusively in genus Mycobacterium, accounts for ∼10% of the M. tuberculosis genome. Our comprehensive in silico analyses of PE/PPE family of H(37)Ra and virulent H(37)Rv strains revealed genetic differences between these strains in terms of several single nucleotide variations and InDels and these manifested in changes in physico-chemical properties, phosphorylation sites, and protein: protein interacting domains of the corresponding proteomes. Similar comparisons using the 13 sigma factor genes, 36 members of the mammalian cell entry family, 13 mycobacterial membrane protein large family members and 11 two-component signal transduction systems along with 5 orphaned response regulators and 2 orphaned sensor kinases failed to reveal very significant difference between H(37)Rv and H(37)Ra, reinforcing the importance of PE/PPE genes. Many of these changes between H(37)Rv and H(37)Ra can be correlated to differences in pathogenesis and virulence of the two strains.

Pleomorphism in Biological Units of Life: Morphological Heterogeneity in Cells Does Not Translate Uniformly to Subcellular Components.

The interplay of the three-dimensional (3D) distribution of various subcellular components and their interactions are expected to control overall cellular morphology in biology. In this study, we aimed to determine whether the pleomorphy observed at the whole-cell level is being reflected by the components constituting the cells by focusing on the 3D distribution of pixel intensities at the single-cell level of the whole (cell) and its parts (the seven subcellular components of the cells-self-assemblies of smaller units). We rigorously acquired and analyzed the image data of RAW264.7 cells at the single-cell level. We report asymmetries in the spatial distribution of pixel intensities at the whole-cell and subcellular component levels along with the occurrence of alterations when pleomorphism is reduced by synchronization of the cell cycle. From our repertoire of seven subcellular components, we report ER, mitochondria, and tubulin to be independent of whole-cell apico-basal heterogeneity of optical density while nuclear, plasma membrane, lysosomal, and actin fluorescence distributions are found to contribute to the apico-basal polarity of the whole cell. While doing so, we have also developed an image analysis algorithm utilizing 2D segmentation to analyze the single cells in 3D using confocal microscopy, a technique that allows us to analyze cellular states in their native hydrated state.

(Re-)Viewing Role of Intracellular Glucose Beyond Extracellular Regulation of Glucose-Stimulated Insulin Secretion by Pancreatic Cells.

For glucose-stimulated insulin secretion (GSIS) by pancreatic ß-cells in animals, it is believed that ATP generated from glucose metabolism is primarily responsible. However, this ignores two well-established aspects in literature: (a) intracellular ATP generation from other sources resulting in an overall pool of ATP, regardless of the original source, and (b) that intracellular glucose transport is 10- to 100-fold higher than intracellular glucose phosphorylation in ß-cells. The latter especially provides an earlier unaddressed, but highly appealing, observation pertaining to (at least transient) the presence of intracellular glucose molecules. Could these intracellular glucose molecules be responsible for the specificity of GSIS to glucose (instead of the widely believed ATP production from its metabolism)? In this work, we provide a comprehensive compilation of literature on glucose and GSIS using various cellular systems - all studies focus only on the extracellular role of glucose in GSIS. Further, we carried out a comprehensive analysis of differential gene expression in Mouse Insulinoma 6 (MIN6) cells, exposed to low and high extracellular glucose concentrations (EGC), from the existing whole transcriptome data. The expression of other genes involved in glycolysis, Krebs cycle, and electron transport chain was found to be unaffected by EGC, except Gapdh, Atp6v0a4, and Cox20. Remarkably, 3 upregulated genes (Atp6v0a4, Cacnb4, Kif11) in high EGC were identified to have an association with cellular secretion. Using glucose as a possible ligand for the 3 proteins, computational investigations were carried out (that will require future 'wet validation', both in vitro and in vivo, e.g., using primary islets and animal models). The glucose-affinity/binding scores (in kcal/mol) obtained were also compared with glucose binding scores for positive controls (GCK and GLUT2), along with negative controls (RPA1, KU70-80, POLA1, ACAA1A, POLR1A). The binding affinity scores of glucose molecules for the 3 proteins were found to be closer to positive controls. Therefore, we report the glucose binding ability of 3 secretion-related proteins and a possible direct role of intracellular glucose molecules in GSIS.

Subarachnoid Hemorrhage Outcomes in an Endovascular Right of First Refusal Neurosurgical Environment.

BACKGROUND: Randomized controlled trials demonstrate that endovascular techniques yield improved outcomes compared with microsurgical approaches. However, not all patients are suitable candidates for endovascular management. This study aimed to determine if healthy patients managed microsurgically could achieve functional outcomes comparable to patients managed endovascularly. METHODS: Patients treated for ruptured aneurysmal subarachnoid hemorrhage at 2 level 1 stroke centers from January 2012 through December 2020 were retrospectively reviewed. All cases were evaluated in an endovascular right of first refusal neurosurgical environment. We collected relevant clinical and follow-up data and created a generalized linear model to identify differences between patients treated endovascularly versus microsurgically. A propensity score model accounting for these differences was used to predict patient outcomes. Functional outcomes were independently assessed using the modified Rankin Scale (mRS) with good functional outcome defined as modified Rankin Scale score <3. RESULTS: The study included 588 patients (211 microsurgical, 377 endovascular); median age was 58 years (interquartile range: 40-86 years); in-hospital mortality was 13%. Age, aneurysm size, and aneurysm location significantly predicted treatment modality (all P < 0.05). After greedy-type matching (210 microsurgical, 210 endovascular), patients managed microsurgically were less likely to be discharged home (odds ratio = 0.6, 95% confidence interval 0.4-0.9, P = 0.01). Functional differences disappeared over time; patients in the 2 treatment arms had similar functional outcomes at 3 months (odds ratio = 1.1, 95% confidence interval 0.7-1.8, P = 0.66) and 1 year after subarachnoid hemorrhage (odds ratio = 1.3, 95% confidence interval 0.8-2.1, P = 0.38). CONCLUSIONS: In an endovascular right of first refusal neurosurgical environment, practitioners can treat patients who are not good endovascular candidates microsurgically and achieve functional outcomes comparable to patients managed endovascularly.

Automated Preoperative and Postoperative Volume Estimates Risk of Retreatment in Chronic Subdural Hematoma: A Retrospective, Multicenter Study.

BACKGROUND AND OBJECTIVES: Several neurosurgical pathologies, ranging from glioblastoma to hemorrhagic stroke, use volume thresholds to guide treatment decisions. For chronic subdural hematoma (cSDH), with a risk of retreatment of 10%-30%, the relationship between preoperative and postoperative cSDH volume and retreatment is not well understood. We investigated the potential link between preoperative and postoperative cSDH volumes and retreatment. METHODS: We performed a retrospective chart review of patients operated for unilateral cSDH from 4 level 1 trauma centers, February 2009-August 2021. We used a 3-dimensional deep learning, automated segmentation pipeline to calculate preoperative and postoperative cSDH volumes. To identify volume thresholds, we constructed a receiver operating curve with preoperative and postoperative volumes to predict cSDH retreatment rates and selected the threshold with the highest Youden index. Then, we developed a light gradient boosting machine to predict the risk of cSDH recurrence. RESULTS: We identified 538 patients with unilateral cSDH, of whom 62 (12%) underwent surgical retreatment within 6 months of the index surgery. cSDH retreatment was associated with higher preoperative (122 vs 103 mL; P < .001) and postoperative (62 vs 35 mL; P < .001) volumes. Patients with >140 mL preoperative volume had nearly triple the risk of cSDH recurrence compared with those below 140 mL, while a postoperative volume >46 mL led to an increased risk for retreatment (22% vs 6%; P < .001). On multivariate modeling, our model had an area under the receiver operating curve of 0.76 (95% CI: 0.60-0.93) for predicting retreatment. The most important features were preoperative and postoperative volume, platelet count, and age. CONCLUSION: Larger preoperative and postoperative cSDH volumes increase the risk of retreatment. Volume thresholds may allow identification of patients at high risk of cSDH retreatment who would benefit from adjunct treatments. Machine learning algorithm can quickly provide accurate estimates of preoperative and postoperative volumes.

Advances in biomarkers for vasospasm - Towards a future blood-based diagnostic test.

Objective: Cerebral vasospasm and the resultant delayed cerebral infarction is a significant source of mortality following aneurysmal SAH. Vasospasm is currently detected using invasive or expensive imaging at regular intervals in patients following SAH, thus posing a risk of complications following the procedure and financial burden on these patients. Currently, there is no blood-based test to detect vasospasm. Methods: PubMed, Web of Science, and Embase databases were systematically searched to retrieve studies related to cerebral vasospasm, aneurysm rupture, and biomarkers. The study search dated from 1997 to 2022. Data from eligible studies was extracted and then summarized. Results: Out of the 632 citations screened, only 217 abstracts were selected for further review. Out of those, only 59 full text articles met eligibility and another 13 were excluded. Conclusions: We summarize the current literature on the mechanism of cerebral vasospasm and delayed cerebral ischemia, specifically studies relating to inflammation, and provide a rationale and commentary on a hypothetical future bloodbased test to detect vasospasm. Efforts should be focused on clinical-translational approaches to create such a test to improve treatment timing and prediction of vasospasm to reduce the incidence of delayed cerebral infarction.