Surgeon-led improvement in compliance with use of sequential compression devices in a neurosurgery patient population.

INTRODUCTION: Sequential compression devices (SCDs) are the mainstay of mechanical prophylaxis for venous thromboembolism in perioperative neurosurgical patients and are especially crucial when chemical prophylaxis is contraindicated. OBJECTIVES: This study aimed to characterise and improve SCD compliance in neurosurgery stepdown patients. METHODS: SCD compliance in a neurosurgical stepdown unit was tracked across 13 months (August 2022-August 2023). When not properly functioning, the missing element was documented. Compliance was calculated daily in all patients with SCD orders, and then averaged monthly. Most common barriers to compliance were identified. With nursing, we implemented a best practice alert to facilitate nursing education at month 3 and tracked compliance over 9 months, with two breaks in surveillance. At month 12, we implemented a patient-engagement measure through creating and distributing a patient-directed infographic and tracked compliance over 2 months. RESULTS: Compliance averaged 19.7% (n=95) during August and 38.4% (n=131) in September. After implementing the best practice alert and supply chain upgrades, compliance improved to 48.8% (n=150) in October, 41.2% (n=104) in March and 45.9% (n=76) in April. The infographic improved compliance to 51.4% (n=70) in July and 55.1% (n=34) in August. Compliance was significantly increased from baseline in August to October (z=4.5838, p<0.00001), sustained through March (z=3.2774, p=0.00104) and further improved by August (z=3.9025, p=0.0001). CONCLUSION: Beyond an initial Hawthorne effect, implementation of the best practice nursing alert facilitated sustained improvement in SCD compliance despite breaks in surveillance. SCD compliance nonetheless remained below 50% until implementation of patient-engagement measures which were dependent on physician involvement.

mcTFI QSM MRI ABC/2 intracranial hemorrhage to noncontrast head CT volume measurement equivalence.

BACKGROUND/OBJECTIVES: Intracranial hemorrhage (ICH) volume assessment is an important part of patient management and is routinely obtained by non-contrast head CT (NCHCT) using the validated ABC/2 measurement method. Because conventional MRI imaging sequences demonstrate variability in ICH appearance, volumetric analyses for MRI bleed volume in a standardized manner using ABC/2 is not possible. The recently introduced multiecho-complex total field inversion quantitative susceptibility mapping (mcTFI QSM) MRI technique, which maps brain tissue susceptibility to both depict brain tissue structures and quantify tissue susceptibility, may provide a viable alternative. In this study we evaluated mcTFI QSM ABC/2 ICH volume assessment relative to NCHCT. METHODS: Patients with ICH who had undergone NCHCT and MRI brain scans within 48 h were recruited for this retrospective study. The ABC/2 method was applied to estimate the bleed volume for both NCHCT and MRI by a CAQ-certified neuroradiologist with 10 years of experience and a trained laboratory assistant. Results were analyzed via Bland-Altman (B-A) and linear regression. RESULTS: 54 patients (27 females) who had undergone NCHCT and MRI within 48 h (<24 h., n = 31, 24-48 h, n = 10) were enrolled. mcTFI QSM ICH volume measurement method showed a positive correlation (99.5%) compared to NCHCT. B-A plot comparing ABC/2 ICH volume on NCHCT and mcTFI MRI done for patients within 24 h demonstrates a bias of -0.09%. CONCLUSIONS: ICH volume calculation using ABC/2 on mcTFI QSM showed a high correlation with NCHCT measurement. These results suggest mcTFI QSM is a promising MRI method for ABC/2 for bleed volume measurement.

Surgery in octogenarians with intracranial meningiomas improves functional outcome at 1 year.

PURPOSE: The population is aging, and age remains an important factor in deciding surgical candidacy for intracranial tumors. The natural history and surgical behavior of meningiomas in octogenarians are not well understood. We evaluated the surgical and functional outcomes, including survival, among octogenarians with intracranial meningiomas in a single institution. METHODS: The Tumor Registry (2004-2021) was used to identify octogenarian patients (ages 80-89) diagnosed with intracranial meningioma. Primary endpoints were 1-year survival and functional outcome measured with mRS postsurgery. Kaplan-Meier, univariable Log-rank tests, and multivariable Cox hazards proportional regression models were used for assessing factors associated with overall survival (OS) in octogenarians with meningiomas who underwent surgery; logistic regression and McNemar's were used to further characterize risk factors affecting functional surgical outcome at 1 year. RESULTS: Thirty octogenarians with intracranial meningioma who underwent surgery were identified. Median age was 82.5 years and 66.6% were female patients. The 1-year median postsurgical survival probability for all octogenarians with meningioma was 86.3% and no intraoperative mortality was observed. Frailty (mFI-5, p = 0.84), tumor grade (p = 0.11), tumor size (p = 0.22), extent of resection (p = 0.35), and Karnofsky scale on admission (p = 0.93) did not significantly affect the survival in octogenarians with meningiomas which were treated surgically. The 1-year postoperative functional status of octogenarian meningioma patients who underwent surgery was significantly improved compared to pre-op mRS (McNemar's chi-squared = 9.6, df = 1, p-value = 0.001946). CONCLUSION: In octogenarians with meningiomas, surgical intervention significantly improves the pre-operative modified Rankin Scale at 1 year postsurgery in this cohort.

Octogenarian Brain Tumor Registry: Single-Institution Surgical Outcomes and Mortality Study.

BACKGROUND: Surgical intervention for brain tumor patients aged 80 to 89 years is controversial, as the comorbidities and physiology associated with aging are often thought to increase surgical risks. Surgical outcomes, however, are not well characterized for octogenarians. This review therefore assessed the outcomes and mortality risk associated with tumor removal in octogenarians at our academic institution. METHODS: Retrospective review of patients aged 80 to 89 who underwent craniotomy for tumor resection (CTR) at our institution between 2004-2021 and who were diagnosed with meningioma, glioblastoma, or metastatic disease. Primary outcome was 30-day mortality. RESULTS: Sixty-one CTRs were included in analysis. Median age was 83 (interquartile range 81-85) years, and the most common preoperative comorbidity was hypertension (n=44). Most patients (n=35) had a preoperative modified Rankin Scale (mRS) score between 0-2. Seventeen (27.9%) patients experienced postoperative complications (i.e., urinary tract infection, deep venous thrombosis, etc.), and 26.2% (n=16) experienced new-onset neurologic deficits postoperatively (i.e., aphasia, motor deficits, etc.). Upon discharge, most patients (n=43) had an mRS score of 3-4. Within 30 days of surgery, 14.8% (n=9) of patients were readmitted to the hospital and 8.2% (n=5) of patients died: 2 with meningioma, 1 with glioblastoma, and 2 with metastatic disease. The most common cause of death was intracranial hemorrhage (n=3). Three-month mortality was 23.0% (n=14). Mean survival after surgery was 33 months for meningioma patients, 6.9 months for glioblastoma patients, and 15 months for patients with metastatic lesions. CONCLUSION: Our review found a 30-day mortality rate of 8.2% across all tumor types, and mean survival was similar to that previously reported for patients across all age groups. Surgical intervention for octogenarian tumor patients is therefore feasible, safe, and likely worthwhile for extending and improving lives.

Quantitative susceptibility mapping improves cerebral microbleed detection relative to susceptibility-weighted images.

BACKGROUND AND PURPOSE: Cerebral microbleed (CMB) detection impacts disease diagnosis and management. Susceptibility-weighted imaging (SWI) MRI depictions of CMBs are used with phase images (SWIP) to distinguish blood from calcification, via qualitative intensity evaluation (bright/dark). However, the intensities depicted for a single lesion can vary within and across consecutive SWIP image planes, impairing the classification of findings as a CMB. We hypothesize that quantitative susceptibility mapping (QSM) MRI, which maps tissue susceptibility, demonstrates less in- and through-plane intensity variation, improving the clinician's ability to categorize a finding as a CMB. METHODS: Forty-eight patients with acute intracranial hemorrhage who received multi-echo gradient echo MRI used to generate both SWI/SWIP and morphology-enabled dipole inversion QSM images were enrolled. Five hundred and sixty lesions were visually classified as having homogeneous or heterogeneous in-plane and through-plane intensity by a neuroradiologist and two diagnostic radiology residents using published rating criteria. When available, brain CT scans were analyzed for calcification or acute hemorrhage. Relative risk (RR) ratios and confidence intervals (CIs) were calculated using a generalized linear model with log link and binary error. RESULTS: QSM showed unambiguous lesion signal intensity three times more frequently than SWIP (RR = 0.3235, 95% CI 0.2386-0.4386, p<.0001). The probability of QSM depicting homogeneous lesion intensity was three times greater than SWIP for small (RR = 0.3172, 95% CI 0.2382-0.4225, p<.0001), large (RR = 0.3431, 95% CI 0.2045-0.5758, p<.0001), lobar (RR = 0.3215, 95% CI 0.2151-0.4805, p<.0001), cerebellar (RR = 0.3215, 95% CI 0.2151-0.4805, p<.0001), brainstem (RR = 0.3100, 95% CI 0.1192-0.8061, p = .0163), and basal ganglia (RR = 0.3380, 95% CI 0.1980-0.5769, p<.0001) lesions. CONCLUSIONS: QSM more consistently demonstrates interpretable lesion intensity compared to SWIP as used for distinguishing CMBs from calcification.

Intracranial venous malformation masquerading as a meningioma in PI3KCA-related overgrowth spectrum disorder.

Gain of function PIK3CA pathogenic variants have been identified in overgrowth syndromes collectively termed "PIK3CA-related overgrowth spectrum" (PROS). There are no previously reported cases of cerebrovascular venous malformations in PROS syndromes, though somatic activating PIK3CA variants have been identified in extracranial venous malformation. This study was approved by the Institutional Review Boar at Boston Children's Hospital. A 14-year-old female mosaic for the de novo p.R108H pathogenic variant in the PIK3CA gene was found to have a large tumor involving the superior sagittal sinus with mass effect on the motor cortex most consistent with a parafalcine meningioma. She underwent surgical resection with pathology demonstrating a venous malformation. PIK3CA pathogenic variants have been identified in nonsyndromic extracranial venous and lymphatic malformations as well in brain tumors, including glioma and meningioma. However, PIK3CA variants have not previously been identified in purely intracranial venous malformations. This distinction is relevant to treatment decisions, given that mTOR inhibitors may provide an alternative option for noninvasive therapy in cases of suspected venous malformation.

"Craniotomy Within Craniotomy" Technique for Safe Resection of an Intracranial Arteriovenous Malformation With Frontal Bony Erosion: 2-Dimensional Operative Video.

Surgical resection is one option in the treatment of large high-grade brain arteriovenous malformations (AVMs). Resection of AVMs with skull-eroding components can be challenging due to the risk of excessive bleeding from these components during craniotomy and bone flap removal. We present a case of a 25-yr-old woman who presented with an acute onset right-sided frontal headache. She was found to have a large, frontal Spetzler-Martin grade IV AVM with an associated dural AVM. The AVM had caused focal erosions of the right frontal bone by a venous varix traversing the region of the calvarial defect. An elective staged endovascular embolization followed by surgical resection was recommended considering the patient's young age and the large size of the AVM located in a noneloquent area. Given the high risk of intraoperative hemorrhage during the craniotomy portion of the procedure, a "craniotomy within craniotomy" approach was planned. During this approach, a small rectangle of bone, including the portion eroded by the venous varix, was left in place, while the larger bone flap surrounding it was removed for an initial approach to the AVM. The small bony piece was safely removed at later stages of resection once the arterial feeders had been reasonably obliterated. Immediate postoperative catheter angiogram demonstrated good filling of the intracranial vascular territories with no residual AVM. The patient developed mild left facial and left hand weakness postoperatively, which resolved after 2 wk of follow-up. The patient remained neurologically intact on further follow-up.

Quantitative Susceptibility Mapping for Staging Acute Cerebral Hemorrhages: Comparing the Conventional and Multiecho Complex Total Field Inversion magnetic resonance imaging MR Methods.

BACKGROUND: The perceived acuity of intracerebral hemorrhage (ICH) impacts the management of patients, both within emergent and outpatient/urgent settings. Morphology enabled dipole inversion (MEDI) quantitative susceptibility imaging (QSM) has improved characterization of ICH acuity, despite outstanding limitations in distinguishing blood products. PURPOSE/HYPOTHESIS: Using improved susceptibility quantification, novel postprocessing QSM method from multiecho complex total field inversion (mcTFI) may better discriminate between acute and subacute ICH, compared to MEDI. STUDY TYPE: Retrospective cohort study. SUBJECTS: A total of 121 subjects enrolled following positive computerized tomography (CT) findings for ICH. Subjects were grouped based on time between admission and MR imaging: hyperacute (<24 hours), acute (1-3 days), early subacute (3-7 days), and late subacute (7-18 days). FIELD STRENGTH/SEQUENCE: A multiecho gradient echo sequence at 3.0 T was paired with clinical noncontrast CT imaging. ASSESSMENT: A quantitative index (CTindex ) was derived based on relative intensities of blood on noncontrast CT. All images were co-registered, from which QSM parameters within the ICH area were assessed across groups, as well as the correlation with CTindex . STATISTICAL TESTS: Group differences were assessed using ANOVAs. Linear regressions between the CTindex , MEDI, and mcTFI measurements were used to assess their relationships. Statistical significance was set at P < 0.05. RESULTS: A total of 21 hyperacute, 72 acute, 21 early subacute, and 7 late-subacute patients were included in this analysis. Significant changes in blood susceptibility were found over time for the MEDI and mcTFI, although mcTFI better differentiated the hyperacute/acute from subacute stages. CTindex values within the ICH were more strongly correlated with mcTFI QSM (r = 0.727) than MEDI (r = 0.412) QSM. DATA CONCLUSION: McTFI susceptibility estimation demonstrated better correlation with ICH acuity as suggested by CT, providing an improved method to assess acuity of intracranial blood products in clinical settings to identify cases that may require acute intervention. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Automated Lateral Ventricular and Cranial Vault Volume Measurements in 13,851 Patients Using Deep Learning Algorithms.

BACKGROUND: No large dataset-derived standard has been established for normal or pathologic human cerebral ventricular and cranial vault volumes. Automated volumetric measurements could be used to assist in diagnosis and follow-up of hydrocephalus or craniofacial syndromes. In this work, we use deep learning algorithms to measure ventricular and cranial vault volumes in a large dataset of head computed tomography (CT) scans. METHODS: A cross-sectional dataset comprising 13,851 CT scans was used to deploy U-Net deep learning networks to segment and quantify lateral cerebral ventricular and cranial vault volumes in relation to age and sex. The models were validated against manual segmentations. Corresponding radiologic reports were annotated using a rule-based natural language processing framework to identify normal scans, cerebral atrophy, or hydrocephalus. RESULTS: U-Net models had high fidelity to manual segmentations for lateral ventricular and cranial vault volume measurements (Dice index, 0.878 and 0.983, respectively). The natural language processing identified 6239 (44.7%) normal radiologic reports, 1827 (13.1%) with cerebral atrophy, and 1185 (8.5%) with hydrocephalus. Age-based and sex-based reference tables with medians, 25th and 75th percentiles for scans classified as normal, atrophy, and hydrocephalus were constructed. The median lateral ventricular volume in normal scans was significantly smaller compared with hydrocephalus (15.7 vs. 82.0 mL; P < 0.001). CONCLUSIONS: This is the first study to measure lateral ventricular and cranial vault volumes in a large dataset, made possible with artificial intelligence. We provide a robust method to establish normal values for these volumes and a tool to report these on CT scans when evaluating for hydrocephalus.

A Spectral Approach to Model-Based Noninvasive Intracranial Pressure Estimation.

BACKGROUND: Intracranial pressure (ICP) normally ranges from 5 to 15 mmHg. Elevation in ICP is an important clinical indicator of neurological injury, and ICP is therefore monitored routinely in several neurological conditions to guide diagnosis and treatment decisions. Current measurement modalities for ICP monitoring are highly invasive, largely limiting the measurement to critically ill patients. An accurate noninvasive method to estimate ICP would dramatically expand the pool of patients that could benefit from this cranial vital sign. METHODS: This article presents a spectral approach to model-based ICP estimation from arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) measurements. The model captures the relationship between the ABP, CBFV, and ICP waveforms and utilizes a second-order model of the cerebral vasculature to estimate ICP. RESULTS: The estimation approach was validated on two separate clinical datasets, one recorded from thirteen pediatric patients with a total duration of around seven hours, and the other recorded from five adult patients, one hour and 48 minutes in total duration. The algorithm was shown to have an accuracy (mean error) of 0.4 mmHg and -1.5 mmHg, and a precision (standard deviation of the error) of 5.1 mmHg and 4.3 mmHg, in estimating mean ICP (range of 1.3 mmHg to 24.8 mmHg) on the pediatric and adult data, respectively. These results are comparable to previous results and within the clinically relevant range. Additionally, the accuracy and precision in estimating the pulse pressure of ICP on a beat-by-beat basis were found to be 1.3 mmHg and 2.9 mmHg respectively. CONCLUSION: These contributions take a step towards realizing the goal of implementing a real-time noninvasive ICP estimation modality in a clinical setting, to enable accurate clinical-decision making while overcoming the drawbacks of the invasive ICP modalities.

Factors Predictive of Adjacent Segment Disease After Lumbar Spinal Fusion.

OBJECTIVE: Adjacent segment disease (ASD) is a long-term complication of lumbar spinal fusion. This study aims to evaluate demographic and operative factors that influence development of ASD after fusion for lumbar degenerative pathologies. METHODS: A retrospective cohort study was performed on patients undergoing instrumented lumbar fusion for degenerative disorders (spondylolisthesis, stenosis, or intervertebral disk degeneration) with a minimum follow-up of 6 months. RESULTS: Our inclusion criteria were met by 568 patients; 29.4% of patients had developed surgical ASD. Median follow-up was 2.8 years. Multivariate logistic regression analysis showed that decompression of segments outside the fusion construct had higher ASD (odds ratio = 2.6; P < 0.001), and those undergoing fusion for spondylolisthesis had lower ASD (odds ratio = 0.47; P = 0.003). CONCLUSIONS: Results of our study show that the most important surgical factor contributing to ASD is decompression beyond fused levels. Hence caution should be exercised when decompressing spinal segments outside the fusion construct. Conversely, spondylolisthesis patients had the lowest ASD rates in our cohort.

A Frequency-domain Approach to Noninvasive Intracranial Pressure Estimation.

Intracranial pressure (ICP) is a cranial vital sign, crucial in the monitoring and treatment of several neurological injuries. The clinically accepted measurement modalities of ICP are highly invasive, carrying risks of infection and limiting the benefits of ICP measurement to a small subset of critically ill patients. This work aims to take a step towards developing an accurate noninvasive means of estimating ICP, by utilizing a model-based frequency-domain approach. The mean ICP and pulse pressures of ICP are estimated from arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) waveforms, and the estimates are validated on an adult population, comprising of around two hours of data from five patients. The algorithm was shown to have an accuracy (mean error) of -1.5 mmHg and a precision (standard deviation of the error) of 4.3 mmHg in estimating the mean ICP. These results are comparable to the previously reported errors among the currently accepted invasive measurement methods, and well within the clinically relevant range.

Intracranial hypertension after Chiari decompression resolving after removal of a levonorgestrel-releasing intrauterine device: case report.

Levonorgestrel-releasing intrauterine devices (LIUDs) are thought to release this progestin locally in the uterus to limit side effects. Authors here present a case of treatment-refractory hydrocephalus and pseudomeningocele (PMC), both of which fully resolved after LIUD removal.A 35-year-old woman with an implanted LIUD developed symptomatic PMC and hydrocephalus after suboccipital craniectomy for Chiari malformation type I. Over the next 8 months, she underwent ventriculoperitoneal shunt placement and two attempts at needle decompression of the fluid collection, which did not relieve her symptoms or the PMC, except for a few days at a time. Subsequently, she had her LIUD removed. Three weeks after removal of the LIUD, her symptoms as well as the fluid collection resolved completely without any further intervention. Thus, the increased intracranial pressure and associated persistence of the PMC may be partially attributed to the LIUD.This case indicates that a persistent problem (PMC and intracranial hypertension) that may be associated with the LIUD rapidly resolves after its removal. Implication of LIUDs as the cause of intracranial hypertension is still a matter of controversy. Further studies are needed to evaluate any potential causal relationship between LIUDs and intracranial hypertension, and physicians are advised to consider this scenario in their differential diagnosis.

Civilian Gunshot Wounds to the Head: Prognostic Factors Affecting Mortality: Meta-Analysis of 1774 Patients.

Civilian gunshot wounds to the head (cGSWH) are devastating, but there is no consensus regarding prognosis and management. Therefore, we conducted a meta-analysis to identify prognostic factors associated with mortality. PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library were queried for retrospective cohort studies of isolated cGSWH reporting mortality prognostic factors. Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were followed. Study quality was assessed using the Newcastle-Ottawa scale. Primary outcome was mortality. Pooled estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were derived using random-effects models. Seventeen (17) observational studies (1774 patients) were identified and included. Factors associated with mortality were: age >40 years (OR, 3.44; 95% CI [1.71-6.91]), suicide attempt (5.78; [3.07-10.87]), Glasgow Coma Scale (GCS) 3-8 compared with 9-15 (38.02; [21.98-65.77]), GCS 3-5 versus 6-8 (15.38; [6.72-35.23], bilateral fixed and dilated pupils versus normal (67.12; [16.67-270.22]), and versus unilateral fixed and dilated pupil (25.35; [5.82-110.41]), dural penetration (29.07; [4.30-196.53]) and bihemispheric (4.23; [2.32-7.68]), and multi-lobar injuries (6.53; [1.99-21.42]). Selection for operative management, according to expert neurosurgical opinion, was protective (0.06; [0.01-0.22]). This is the first meta-analysis on cGSWH mortality prognostic factors. Increasing age, suicide attempt, lower GCS, bilateral mydriasis, dural penetration, and bihemispheric and multi-lobar injury are associated with increased mortality. This study can serve as a guide to clinicians and will provide directions for future research to develop evidence-based management algorithms.

A Waveform Archiving System for the GE Solar 8000i Bedside Monitor.

OBJECTIVES: Our objective was to develop, deploy, and test a data-acquisition system for the reliable and robust archiving of high-resolution physiological waveform data from a variety of bedside monitoring devices, including the GE Solar 8000i patient monitor, and for the logging of ancillary clinical and demographic information. MATERIALS AND METHODS: The data-acquisition system consists of a computer-based archiving unit and a GE Tram Rac 4A that connects to the GE Solar 8000i monitor. Standard physiological front-end sensors connect directly to the Tram Rac, which serves as a port replicator for the GE monitor and provides access to these waveform signals through an analog data interface. Together with the GE monitoring data streams, we simultaneously collect the cerebral blood flow velocity envelope from a transcranial Doppler ultrasound system and a non-invasive arterial blood pressure waveform along a common time axis. All waveform signals are digitized and archived through a LabView-controlled interface that also allows for the logging of relevant meta-data such as clinical and patient demographic information. RESULTS: The acquisition system was certified for hospital use by the clinical engineering team at Boston Medical Center, Boston, MA, USA. Over a 12-month period, we collected 57 datasets from 11 neuro-ICU patients. The system provided reliable and failure-free waveform archiving. We measured an average temporal drift between waveforms from different monitoring devices of 1 ms every 66 min of recorded data. CONCLUSIONS: The waveform acquisition system allows for robust real-time data acquisition, processing, and archiving of waveforms. The temporal drift between waveforms archived from different devices is entirely negligible, even for long-term recording.

Intraocular Silicone Oil Migration into the Ventricles Resembling Intraventricular Hemorrhage: Case Report and Review of the Literature.

BACKGROUND: Intracranial silicone migration is a rare complication of ocular silicone oil endotamponade and may resemble intraventricular hemorrhage. The etiology of the phenomenon is challenging to understand. CASE DESCRIPTION: In an effort to shed light on this phenomenon, we report a case of a 67-year-old woman with ocular silicone oil endotamponade on the left eye due to retinal detachment who presented with headache to the emergency department. The imaging work-up revealed intraventricular silicone oil migration. CONCLUSIONS: The literature is reviewed through the perspective of pathophysiology. The migration of intraocular silicone oil into the ventricular system provides both an important complication for clinicians to be aware of, as well as a paradigm reminding us that cerebrospinal fluid spaces may have more extensive communications with other body compartments than previously thought.

Aquaporins in Brain Edema and Neuropathological Conditions.

The aquaporin (AQP) family of water channels are a group of small, membrane-spanning proteins that are vital for the rapid transport of water across the plasma membrane. These proteins are widely expressed, from tissues such as the renal epithelium and erythrocytes to the various cells of the central nervous system. This review will elucidate the basic structure and distribution of aquaporins and discuss the role of aquaporins in various neuropathologies. AQP1 and AQP4, the two primary aquaporin molecules of the central nervous system, regulate brain water and CSF movement and contribute to cytotoxic and vasogenic edema, where they control the size of the intracellular and extracellular fluid volumes, respectively. AQP4 expression is vital to the cellular migration and angiogenesis at the heart of tumor growth; AQP4 is central to dysfunctions in glutamate metabolism, synaptogenesis, and memory consolidation; and AQP1 and AQP4 adaptations have been seen in obstructive and non-obstructive hydrocephalus and may be therapeutic targets.

Sestrin-2 is significantly increased in malignant pleural effusions due to lung cancer and is potentially secreted by pleural mesothelial cells.

OBJECTIVES: Sestrin-2 (Sesn2) belongs to a family of highly conserved antioxidant proteins that were discovered as p53-inducible proteins and inhibits cell growth and proliferation. Our aim was to assess the levels of Sesn2 in malignant pleural effusions of lung cancer patients compared to benign pleural effusions. DESIGN AND METHODS: We enrolled 73 patients (55/males and 18/females) diagnosed with pleural effusion (PE). PEs were grouped as 44 malignant pleural effusions (MPEs; lung cancer) and 29 benign (BPE; 7 congestive heart failure, 9 tuberculosis, 13 parapneumonic). Pleural fluid (PF) Sesn2 levels were determined by enzyme-linked immunosorbent assay (ELISA) kit. Standard biochemical PF analysis was also performed and Sesn2 levels were correlated with PF lactate dehydrogenase (LDH), protein, cell counts and age. RESULTS: Sesn2 was detected in 24/44 patients with MPEs and in 3/29 patients with BPEs (p=0.0001). The mean value (mean±SEM) of Sesn2 in patients with MPEs was 0.54±0.22ng/mL while in BPEs it was 0.12±0.04ng/mL (p=0.0004). In MPEs Sesn2 pleural fluid levels did not correlate with PF LDH and cell counts (p=0.89 and p=0.64 respectively). CONCLUSIONS: Our study shows that Sesn2 is significantly increased in MPEs compared to BPEs. Moreover, the lack of correlation of Sesn2 levels with PF cell counts and PF LDH suggests that it is potentially secreted by pleural mesothelial cells.