BioASQ Synergy: a dialogue between question-answering systems and biomedical experts for promoting COVID-19 research.

OBJECTIVE: This article presents the novel BioASQ Synergy research process which aims to facilitate the interaction between biomedical experts and automated question-answering systems. MATERIALS AND METHODS: The proposed research allows systems to provide answers to emerging questions, which in turn are assessed by experts. The assessment of the experts is fed back to the systems, together with new questions. With this iteration, we aim to facilitate the incremental understanding of a developing problem and contribute to solution discovery. RESULTS: The results suggest that the proposed approach can assist researchers to navigate available resources. The experts seem to be very satisfied with the quality of the ideal answers provided by the systems, suggesting that such systems are already useful in answering open research questions. DISCUSSION: BioASQ Synergy aspires to provide a tool that gives the experts easy and personalized access to the latest findings in a fast-growing corpus of material. CONCLUSION: In this article, we envisioned BioASQ Synergy as a continuous dialogue between experts and systems to issue open questions. We ran an initial proof-of-concept of the approach, in order to evaluate its usefulness, both from the side of the experts, as well as from the side of the participating systems.

Digital Phenotyping for Monitoring and Disease Trajectory Prediction of Patients With Cancer: Protocol for a Prospective Observational Cohort Study.

BACKGROUND: Timely recognition of cancer progression and treatment complications is important for treatment guidance. Digital phenotyping is a promising method for precise and remote monitoring of patients in their natural environments by using passively generated data from sensors of personal wearable devices. Further studies are needed to better understand the potential clinical benefits of digital phenotyping approaches to optimize care of patients with cancer. OBJECTIVE: We aim to evaluate whether passively generated data from smartphone sensors are feasible for remote monitoring of patients with cancer to predict their disease trajectories and patient-centered health outcomes. METHODS: We will recruit 200 patients undergoing treatment for cancer. Patients will be followed up for 6 months. Passively generated data by sensors of personal smartphone devices (eg, accelerometer, gyroscope, GPS) will be continuously collected using the developed LAIMA smartphone app during follow-up. We will evaluate (1) mobility data by using an accelerometer (mean time of active period, mean time of exertional physical activity, distance covered per day, duration of inactive period), GPS (places of interest visited daily, hospital visits), and gyroscope sensors and (2) sociability indices (frequency of duration of phone calls, frequency and length of text messages, and internet browsing time). Every 2 weeks, patients will be asked to complete questionnaires pertaining to quality of life (European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire [EORTC QLQ-C30]), depression symptoms (Patient Health Questionnaire-9 [PHQ-9]), and anxiety symptoms (General Anxiety Disorder-7 [GAD-7]) that will be deployed via the LAIMA app. Clinic visits will take place at 1-3 months and 3-6 months of the study. Patients will be evaluated for disease progression, cancer and treatment complications, and functional status (Eastern Cooperative Oncology Group) by the study oncologist and will complete the questionnaire for evaluating quality of life (EORTC QLQ-C30), depression symptoms (PHQ-9), and anxiety symptoms (GAD-7). We will examine the associations among digital, clinical, and patient-reported health outcomes to develop prediction models with clinically meaningful outcomes. RESULTS: As of July 2023, we have reached the planned recruitment target, and patients are undergoing follow-up. Data collection is expected to be completed by September 2023. The final results should be available within 6 months after study completion. CONCLUSIONS: This study will provide in-depth insight into temporally and spatially precise trajectories of patients with cancer that will provide a novel digital health approach and will inform the design of future interventional clinical trials in oncology. Our findings will allow a better understanding of the potential clinical value of passively generated smartphone sensor data (digital phenotyping) for continuous and real-time monitoring of patients with cancer for treatment side effects, cancer complications, functional status, and patient-reported outcomes as well as prediction of disease progression or trajectories. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/49096.

Directionally encoded color track density imaging in brain tumor patients: A potential application to neuro-oncology surgical planning.

BACKGROUND: Diffusion magnetic resonance imaging white matter tractography, an increasingly popular preoperative planning modality used for pre-surgical planning in brain tumor patients, is employed with the goal of maximizing tumor resection while sparing postoperative neurological function. Clinical translation of white matter tractography has been limited by several shortcomings of standard diffusion tensor imaging (DTI), including poor modeling of fibers crossing through regions of peritumoral edema and low spatial resolution for typical clinical diffusion MRI (dMRI) sequences. Track density imaging (TDI) is a post-tractography technique that uses the number of tractography streamlines and their long-range continuity to map the white matter connections of the brain with enhanced image resolution relative to the acquired dMRI data, potentially offering improved white matter visualization in patients with brain tumors. The aim of this study was to assess the utility of TDI-based white matter maps in a neurosurgical planning context compared to the current clinical standard of DTI-based white matter maps. METHODS: Fourteen consecutive brain tumor patients from a single institution were retrospectively selected for the study. Each patient underwent 3-Tesla dMRI scanning with 30 gradient directions and a b-value of 1000 s/mm2. For each patient, two directionally encoded color (DEC) maps were produced as follows. DTI-based DEC-fractional anisotropy maps (DEC-FA) were generated on the scanner, while DEC-track density images (DEC-TDI) were generated using constrained spherical deconvolution based tractography. The potential clinical utility of each map was assessed by five practicing neurosurgeons, who rated the maps according to four clinical utility statements regarding different clinical aspects of pre-surgical planning. The neurosurgeons rated each map according to their agreement with four clinical utility statements regarding if the map 1 identified clinically relevant tracts, (2) helped establish a goal resection margin, (3) influenced a planned surgical route, and (4) was useful overall. Cumulative link mixed effect modeling and analysis of variance were performed to test the primary effect of map type (DEC-TDI vs. DEC-FA) on rater score. Pairwise comparisons using estimated marginal means were then calculated to determine the magnitude and directionality of differences in rater scores by map type. RESULTS: A majority of rater responses agreed with the four clinical utility statements, indicating that neurosurgeons found both DEC maps to be useful. Across all four investigated clinical utility statements, the DEC map type significantly influenced rater score. Rater scores were significantly higher for DEC-TDI maps compared to DEC-FA maps. The largest effect size in rater scores in favor of DEC-TDI maps was observed for clinical utility statement 2, which assessed establishing a goal resection margin. CONCLUSION: We observed a significant neurosurgeon preference for DEC-TDI maps, indicating their potential utility for neurosurgical planning.

Stereotactic Radiosurgery for Vestibular Schwannoma in Neurofibromatosis Type 2: An International Multicenter Case Series of Response and Malignant Transformation Risk.

BACKGROUND: Vestibular schwannomas (VSs) related to neurofibromatosis type 2 (NF2) are challenging tumors. The increasing use of stereotactic radiosurgery (SRS) necessitates further investigations of its role and safety. OBJECTIVE: To evaluate tumor control, freedom from additional treatment (FFAT), serviceable hearing preservation, and radiation-related risks of patients with NF2 after SRS for VS. METHODS: We performed a retrospective study of 267 patients with NF2 (328 VSs) who underwent single-session SRS at 12 centers participating in the International Radiosurgery Research Foundation. The median patient age was 31 years (IQR, 21-45 years), and 52% were male. RESULTS: A total of 328 tumors underwent SRS during a median follow-up time of 59 months (IQR, 23-112 months). At 10 and 15 years, the tumor control rates were 77% (95% CI: 69%-84%) and 52% (95% CI: 40%-64%), respectively, and the FFAT rate were 85% (95% CI: 79%-90%) and 75% (95% CI: 65%-86%), respectively. At 5 and 10 years, the serviceable hearing preservation rates were 64% (95% CI: 55%-75%) and 35% (95% CI: 25%-54%), respectively. In the multivariate analysis, age (hazards ratio: 1.03 [95% CI: 1.01-1.05]; P = .02) and bilateral VSs (hazards ratio: 4.56 [95% CI: 1.05-19.78]; P = .04) were predictors for serviceable hearing loss. Neither radiation-induced tumors nor malignant transformation were encountered in this cohort. CONCLUSION: Although the absolute volumetric tumor progression rate was 48% at 15 years, the rate of FFAT related to VS was 75% at 15 years after SRS. None of the patients with NF2-related VS developed a new radiation-related neoplasm or malignant transformation after SRS.

Comparison of the accuracy of the 7-item HADS Depression subscale and 14-item total HADS for screening for major depression: A systematic review and individual participant data meta-analysis.

The seven-item Hospital Anxiety and Depression Scale Depression subscale (HADS-D) and the total score of the 14-item HADS (HADS-T) are both used for major depression screening. Compared to the HADS-D, the HADS-T includes anxiety items and requires more time to complete. We compared the screening accuracy of the HADS-D and HADS-T for major depression detection. We conducted an individual participant data meta-analysis and fit bivariate random effects models to assess diagnostic accuracy among participants with both HADS-D and HADS-T scores. We identified optimal cutoffs, estimated sensitivity and specificity with 95% confidence intervals, and compared screening accuracy across paired cutoffs via two-stage and individual-level models. We used a 0.05 equivalence margin to assess equivalency in sensitivity and specificity. 20,700 participants (2,285 major depression cases) from 98 studies were included. Cutoffs of ≥7 for the HADS-D (sensitivity 0.79 [0.75, 0.83], specificity 0.78 [0.75, 0.80]) and ≥15 for the HADS-T (sensitivity 0.79 [0.76, 0.82], specificity 0.81 [0.78, 0.83]) minimized the distance to the top-left corner of the receiver operating characteristic curve. Across all sets of paired cutoffs evaluated, differences of sensitivity between HADS-T and HADS-D ranged from -0.05 to 0.01 (0.00 at paired optimal cutoffs), and differences of specificity were within 0.03 for all cutoffs (0.02-0.03). The pattern was similar among outpatients, although the HADS-T was slightly (not nonequivalently) more specific among inpatients. The accuracy of HADS-T was equivalent to the HADS-D for detecting major depression. In most settings, the shorter HADS-D would be preferred. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Laser Interstitial Thermal Therapy for the Treatment of Primary and Metastatic Brain Tumors: A Systematic Review and Meta-Analysis.

BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive treatment option for intracranial tumors that are challenging to treat via traditional methods; however, its safety and efficacy are not yet well validated in the literature. The objectives of the study were to assess the available evidence of the indications and adverse events (AEs) of LITT and 1-year progression-free survival and 1-year overall survival in the treatment of primary and secondary brain tumors. METHODS: A comprehensive literature search was conducted through the databases PubMed, Embase, and the Cochrane Library until October 2021. Comparative and descriptive studies, except for case reports, were included in the meta-analysis. Separate analyses by tumor type (high-grade gliomas, including World Health Organization grade 4 astrocytomas [which include glioblastomas] as a specific subgroup; low-grade gliomas; and brain metastases) were conducted. Pooled effect sizes and their 95% confidence intervals (CI) were generated via random-effects models. RESULTS: Forty-five studies met the inclusion criteria, yielding 826 patients for meta-analysis. There were 829 lesions in total, of which 361 were classified as high-grade gliomas, 116 as low-grade gliomas, 337 as metastatic brain tumors, and 15 as nonglial tumors. Indications for offering LITT included deep/inaccessible tumor (12 studies), salvage therapy after failed radiosurgery (9), failures of ≥2 treatment options (3), in pediatric patients (4), patient preference (1); indications were nonspecific in 12 studies. Pooled incidence of all (minor or major) procedure-related AEs was 30% (95% CI, 27%-40%) for all tumors. Pooled incidence of neurologic deficits (minor or major) was 16% (12%-22%); postprocedural edema 14% (8%-22%); seizure 6% (4%-9%); hematoma 20% (14%-29%); deep vein thrombosis 19% (11%-30%); hydrocephalus 8% (5%-12%); and wound infection 5% (3%-7%). One-year progression-free survival was 18.6% (11.3%-29.0%) in high-grade gliomas, 16.9% (11.6%-24.0%) among the grade 4 astrocytomas; and 51.2% (36.7%-65.5%) in brain metastases. One-year overall survival was 43.0% (36.0%-50.0%) in high-grade glioma, 45.9% (95% CI, 37.9%-54%) in grade 4 astrocytomas; 93.0% (42.3%-100%) in low-grade gliomas, and 56.3% (47.0%-65.3%) in brain metastases. CONCLUSIONS: New neurologic deficits and postprocedural edema were the most reported AEs after LITT, albeit mostly transient. This meta-analysis provides the best statistical estimates of progression and survival outcomes based on the available information. LITT is generally a safe procedure for selected patients, and future well-designed comparative studies on its outcomes versus the current standard of care should be performed.

Smartphone sensors for evaluating COVID-19 fear in patients with cancer: a prospective study.

Objective: This study aimed to analyze the association between the behavior of cancer patients, measured using passively and continuously generated data streams from smartphone sensors (as in digital phenotyping), and perceived fear of COVID-19 and COVID-19 vaccination status. Methods: A total of 202 patients with different cancer types and undergoing various treatments completed the COVID-19 Fears Questionnaire for Chronic Medical Conditions, and their vaccination status was evaluated. Patients' behaviors were monitored using a smartphone application that passively and continuously captures high-resolution data from personal smartphone sensors. In all, 107 patients were monitored for at least 2 weeks. The study was conducted between August 2022 and August 2023. Distributions of clinical and demographical parameters between fully vaccinated, partially vaccinated, and unvaccinated patients were compared using the Chi-squared test. The fear of COVID-19 among the groups was compared using the Mann-Whitney and the Kruskal-Wallis criteria. Trajectories of passively generated data were compared as a function of fear of COVID-19 and COVID-19 vaccination status using local polynomial regression. Results: In total, 202 patients were included in the study. Most patients were fully (71%) or partially (13%) vaccinated and 16% of the patients were unvaccinated for COVID-19. Fully vaccinated or unvaccinated patients reported greater fear of COVID-19 than partially vaccinated patients. Fear of COVID-19 was higher in patients being treated with biological therapy. Patients who reported a higher fear of COVID-19 spent more time at home, visited places at shorter distances from home, and visited fewer places of interest (POI). Fully or partially vaccinated patients visited more POI than unvaccinated patients. Local polynomial regression using passively generated smartphone sensor data showed that, although at the beginning of the study, all patients had a similar number of POI, after 1 week, partially vaccinated patients had an increased number of POI, which later remained, on average, around four POI per day. Meanwhile, fully vaccinated or unvaccinated patients had a similar trend of POI and it did not exceed three visits per day during the entire treatment period. Conclusion: The COVID-19 pandemic continues to have an impact on the behavior of cancer patients even after the termination of the global pandemic. A higher perceived fear of COVID-19 was associated with less movement, more time spent at home, less time spent outside of home, and a lower number of visited places. Unvaccinated patients visited fewer places and were moving less overall during a 14-week follow-up as compared to vaccinated patients.

Cortisol response to psychosocial stress, mental distress, fatigue and quality of life in coronary artery disease patients.

We aimed to explore the relationship between cortisol response to psychosocial stress, mental distress, fatigue and health related quality of life (HRQoL) in individuals with coronary artery disease (CAD) after recent acute coronary syndrome (ACS). A cross-sectional study initially included 113 subjects (88% men, 53 ± 7 years) 1-3 weeks after ACS. Cortisol response was assessed by measuring salivary cortisol during Trier Social Stress Test. Mental distress was measured with Hospital Anxiety and Depression Scale, State-Trait Anxiety Inventory, and Type D Scale-14. Fatigue symptoms were evaluated using Multidimensional Fatigue Inventory 20-items, while HRQoL was assessed with 36-Item Short Form Medical Outcome Questionnaire. After conducting multivariable linear regression analyses, diminished cortisol response sampled after Public speech (T3-T1, + 15 min) was significantly associated with higher anxiety symptoms (ß = -0.224; p = 0.035), while diminished cortisol response sampled after preparation time (T2-T1, + 10 min) was significantly linked with the presence of Type D personality (ß = -0.290; p = 0.006; ß = -0.282; p = 0.008 respectively), even after controlling for confounders (i.e., sex, age, education, New York Heart Association functional class, beta-blockers and baseline levels of cortisol measures). We found that mental distress, but not fatigue and HRQoL, was linked with blunted cortisol response during anticipation time of psychosocial stress, independently of potential covariates.

Associations of miR-181a with Health-Related Quality of Life, Cognitive Functioning, and Clinical Data of Patients with Different Grade Glioma Tumors.

Gliomas are central nervous system tumors with a lethal prognosis. Small micro-RNA molecules participate in various biological processes, are tissue-specific, and, therefore, could be promising targets for cancer treatment. Thus, this study aims to examine miR-181a as a potent biomarker for the diagnosis and prognosis of glioma patients and, for the first time, to find associations between the expression level of miR-181a and patient quality of life (QoL) and cognitive functioning. The expression level of miR-181a was analyzed in 78 post-operative II-IV grade gliomas by quantitative real-time polymerase chain reaction. The expression profile was compared with patient clinical data (age, survival time after the operation, tumor grade and location, mutation status of isocitrate dehydrogenase 1 (IDH1), and promoter methylation of O-6-methylguanine methyltransferase). Furthermore, the health-related QoL was assessed using the Karnofsky performance scale and the quality of life questionnaires; while cognitive assessment was assessed by the Hopkins verbal learning test-revised, trail-making test, and phonemic fluency tasks. The expression of miR-181a was significantly lower in tumors of grade III and IV and was associated with IDH1 wild-type gliomas and a worse prognosis of patient overall survival. Additionally, a positive correlation was observed between miR-181a levels and functional status and QoL of glioma patients. Therefore, miR-181a is a unique molecule that plays an important role in gliomagenesis, and is also associated with changes in patients' quality of life.

Contribution of Obstructive Sleep Apnoea to Cognitive Functioning of Males With Coronary Artery Disease: A Relationship With Endocrine and Inflammatory Biomarkers.

Introduction: Our exploratory study aimed to determine whether obstructive sleep apnoea (OSA) could affect cognitive functioning in males with coronary artery disease (CAD), and whether such impact could be associated with changes in thyroid hormones and inflammatory marker regulation on cognitive functioning. Method: We evaluated different endocrine and inflammatory biomarkers, including free triiodothyronine [fT3], free tetraiodothyronine [fT4], N-terminal pro-B-type natriuretic peptide [NT-pro-BNP], and high-sensitivity C-reactive protein [hs-CRP] serum levels in 328 males ( x ¯ = 57 ± 10 years), undergoing cardiac rehabilitation after an acute coronary event. Participants underwent full-night polysomnography and were classified in mild/non-OSA (n = 253) and OSA (n = 75) according to an apnoea-hypopnoea index ≥ 15 event/h. Cognitive functioning testing included the Digit Span Test, Digit Symbol Test (DSST), and Trail Making Test. Analyses of variance assessed the impact of OSA on cognitive functioning and possible relationships of fT3/fT4, NT-pro-BNP and with hs-CRP on cognitive measures. Results: Significant group (OSA, mild/non-OSA) × NT-pro-BNP (<157.0 vs. ≥157.0, ng/L) interactions were found for the DSST raw score (F (2,324) = 3.58, p = 0.014). Decomposition of interactions showed that the DSST scores of the OSA group with NT-pro-BNP ≥ 157.0 ng/L (M = 33.2; SD = 8.1) were significantly lower, p = 0.031, than those of the mild/non-OSA with NT-pro-BNP < 157.0 ng/L (M = 37.7; SD = 8.9). Conclusion: These findings indicate that males with OSA and clinically elevated NT-pro-BNP levels experienced inferior psychomotor performance compared to those without OSA and reduced NT-pro-BNP levels.

Thyroid Hormones and Health-Related Quality of Life in Normal Pressure Hydrocephalus Patients before and after the Ventriculoperitoneal Shunt Surgery: A Longitudinal Study.

OBJECTIVE: The aim of this study was to explore the serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3), and to correlate the hormone levels among iNPH patients with their self-reported quality of life before and three months after the surgery. METHODS: Twenty-five patients (52% women), mean age 63.5 (SD 9.5) years, were operated on by inserting a VP shunt. Patients with FT3 level ≤3.34 pmol/L were diagnosed as having low T3 syndrome. RESULTS: The changes in thyroid hormones resulted in a U-shaped curve throughout the follow-up period. The significant changes occurred the next day after the surgery, including a decrease in TSH, FT3, and an increase in FT4. Additionally, the decrease occurred in mean FT3 for six patients with preoperative low T3 syndrome. Three months after the surgery, thyroid hormones were restored to their baseline and/or normal values. All six patients with preoperative low T3 syndrome had significant improvement in all SF-36 subscales (except for the role emotional and physical). Patients with preoperative normal high FT3 and low FT4 had increased FT3/FT4 ratio which was associated with deterioration in all SF-36 subscales 3 months after the surgery. CONCLUSION: Routine assessment of the FT3/FT4 ratio might be a simple and effective tool for the risk stratification of iNPH patients before VP shunt surgery.

Health related quality of life trajectories after stereotactic radiosurgery for brain metastases: a systematic review.

PURPOSE: Health related quality of life (HRQoL) is often used as an outcome measure of cancer treatment. Stereotactic radiosurgery (SRS) is a mainstay treatment of brain metastases (BMs) with constantly improving treatment envelope. The goal of this systematic review was to evaluated HRQoL trajectories after SRS, identify important predictors of HRQoL after SRS, and to evaluate clinical importance of post-SRS HRQoL trajectories of BM patients treated with SRS. METHODS: A systematic literature review according to the PRISMA guidelines analyzing HRQoL trajectories after SRS for BM published in the Pubmed/MEDLINE database before January, 2022. RESULTS: We identified 18 studies that evaluated HRQoL before and at least once after SRS for BMs. The majority of studies were single-institution retrospective series and included patients with different cancer types. Different instruments were used to assess HRQoL. In the majority of studies (n = 10) at group level, there was no significant change in global HRQoL after SRS. Stability, improvement, and deterioration of HRQoL global and subscale scores at individual patient level were common. Post-SRS HRQoL deterioration was predicted by worse functional status, greater number of BMs, delayed SRS, symptomatic BMs, and presence of seizures and cognitive impairment. Shorter post-SRS survival and adverse radiation effects (AREs) were associated with worse HRQoL. CONCLUSIONS: SRS for BMs is often associated with sustained preservation of HRQoL. Individual variation of HRQoL domains after SRS is common. Shorter survival and AREs are associated with worse HRQoL. Worse functional status and greater disease burden predict unfavorable HRQoL trajectories after SRS for BMs.

Quantitative Evans index estimation using ultrasonographic measurement of the optic nerve sheath diameter in supine and upright position.

OBJECTIVES: We aimed to quantitatively assess Evans index (EI) using ultrasonographic optic nerve sheath diameter (ONSD) measurements in supine and upright position in normal pressure hydrocephalus (NPH) patients. METHODS: Ultrasonographically ONSD was measured in a supine and upright position before and 4-5 days after the ventriculoperitoneal shunt surgery. The changes of the ONSD between supine and upright positions were calculated as ∆ONSD = sONSD-uONSD and as the variation ONSD_V = 100% × [(sONSD - uONSD)/sONSD]. Multiple linear regression analyses were conducted to assess associations between EI and the variation of ONSD. We derived the mathematical function to predict EI. Bland-Altman analysis was applied to evaluate the accuracy and precision of the EI prediction. RESULTS: Thirteen adult patients (mean age 61.8 ± 11.1 (SD) years; 6 (46%) female) undergone VP shunt implantation for NPH. The mean EI was 0.432 (95% CI, 0.393-0.471) preoperatively and 0.419 (95% CI, 0.373-0.466) postoperatively (p = 0.066). There is a decrease of the ONSD during positional changes from supine to upright position and pre- and postoperative EI correlated with preoperative variation ONSD_V1 (r = - 0.610 and - 0.648, p < 0.05). The mathematical function for preoperative EI estimation was EIpreop = 0.504 - 0.022 × ONSD_V1 + 0.101 × gender (M = 0; W = 1), (Durbin-Watson value = 1.94), and for postoperative was EIpostop = 0.487 - 0.022 × ONSD_V1 + 0.117 × gender; (Durbin-Watson value 2.23). CONCLUSIONS: Ultrasonographic ONSD measurements in supine and upright position provide a potential method to quantify EI that can be conducted at the bedside.

Comparison of Active Surveillance to Stereotactic Radiosurgery for the Management of Patients with an Incidental Frontobasal Meningioma-A Sub-Analysis of the IMPASSE Study.

Meningioma is a common incidental finding, and clinical course varies based on anatomical location. The aim of this sub-analysis of the IMPASSE study was to compare the outcomes of patients with an incidental frontobasal meningioma who underwent active surveillance to those who underwent upfront stereotactic radiosurgery (SRS). Data were retrospectively collected from 14 centres. The active surveillance (n = 28) and SRS (n = 84) cohorts were compared unmatched and matched for age, sex, and duration of follow-up (n = 25 each). The study endpoints included tumor progression, new symptom development, and need for further intervention. Tumor progression occurred in 52.0% and 0% of the matched active surveillance and SRS cohorts, respectively (p < 0.001). Five patients (6.0%) treated with SRS developed treatment related symptoms compared to none in the active monitoring cohort (p = 0.329). No patients in the matched cohorts developed symptoms attributable to treatment. Three patients managed with active surveillance (10.7%, unmatched; 12.0%, matched) underwent an intervention for tumor growth with no persistent side effects after treatment. No patients subject to SRS underwent further treatment. Active monitoring and SRS confer a similarly low risk of symptom development. Upfront treatment with SRS improves imaging-defined tumor control. Active surveillance and SRS are acceptable treatment options for incidental frontobasal meningioma.

Stereotactic Radiosurgery Compared With Active Surveillance for Asymptomatic, Parafalcine, and Parasagittal Meningiomas: A Matched Cohort Analysis From the IMPASSE Study.

BACKGROUND: The optimal management of asymptomatic, presumed WHO grade I meningiomas remains controversial. OBJECTIVE: To define the safety and efficacy of stereotactic radiosurgery (SRS) compared with active surveillance for the management of patients with asymptomatic parafalcine/parasagittal (PFPS) meningiomas. METHODS: Data from SRS-treated patients from 14 centers and patients managed conservatively for an asymptomatic, PFPS meningioma were compared. Local tumor control rate and new neurological deficits development were evaluated in the active surveillance and the SRS-treated cohorts. RESULTS: There were 173 SRS-treated patients and 98 patients managed conservatively in the unmatched cohorts. After matching for patient age and tumor volume, there were 98 patients in each cohort. The median radiological follow-up period was 43 months for the SRS cohort and 36 months for the active surveillance cohort (P = .04). The median clinical follow-up for the SRS and active surveillance cohorts were 44 and 36 months, respectively. Meningioma control was noted in all SRS-treated patients and in 61.2% of patients managed with active surveillance (P < .001). SRS-related neurological deficits occurred in 3.1% of the patients (n = 3), which were all transient. In the active surveillance cohort, 2% of patients (n = 2) developed neurological symptoms because of tumor progression (P = 1.0), resulting in death of 1 patient (1%). CONCLUSION: Up-front SRS affords superior radiological PFPS meningioma control as compared with active surveillance and may lower the risk of meningioma-related permanent neurological deficit and/or death.

Stereotactic radiosurgery for Rathke's cleft cysts: an international multicenter study.

OBJECTIVE: Rathke's cleft cysts (RCCs) are sellar collections from an incompletely regressed Rathke's pouch. Common symptoms of RCCs can include headaches, visual loss, and endocrinopathy. Surgery is required in some cases of symptomatic or growing RCCs. Recurrence after surgery is common (range 10%-40%). Stereotactic radiosurgery (SRS) has been used in an attempt to control growth and symptoms, but outcomes are not well known. The authors sought to study the outcomes of RCCs following Gamma Knife surgery for both salvage and initial treatment. METHODS: The outcomes of 25 patients with RCCs who underwent SRS between 2001 and 2020 were reviewed. Four patients received initial SRS and 21 were treated with salvage SRS. Diagnosis was based on imaging or histopathology. Cyst control was defined as stability or regression of the cyst. Kaplan-Meier analysis was used to determine time to recurrence and determine potential factors for recurrence. RESULTS: The respective median clinical follow-up and margin dose were 6.5 years and 12 Gy. Overall control was achieved in 19 (76%) of 25 patients, and 4 recurrences required further intervention. The average time to recurrence was 35.6 months in those RCCs that recurred. Visual recovery occurred in 14 (93.3%) of 15 patients and no new post-SRS visual deficits occurred. The presence of a pretreatment visual deficit was often an indicator of RCC regrowth. All 3 patients with pretreatment hyperprolactinemia experienced resolution after SRS. New endocrinopathy related to SRS was noted in 5 (20%) of 25 patients, all of which were thyroid and/or cortisol axis related. Upfront SRS was used in 4 patients. No new endocrinopathies or visual deficits developed after upfront SRS, and the 1 patient with a pretreatment visual deficit recovered. One of the 4 patients with upfront SRS experienced a recurrence after 7.5 years. CONCLUSIONS: SRS produced effective recovery of visual deficits and carries a low risk for new visual deficits. Cyst control was achieved in approximately three-fourths of the patients. Following SRS, patients without pretreatment visual deficits are less likely to have RCC regrowth. Endocrinopathy can occur after SRS, similar to other sellar mass lesions. Initial SRS shows the potential for long-term cyst control, with improvement of symptoms and a low risk for complications.

Psychometric properties of The COVID-19 Fears Questionnaire for Chronic Medical Conditions in patients with pre-existing medical conditions.

Fear of COVID-19 can have adverse mental health consequences in vulnerable patients with pre-existing conditions. We aimed to validate The COVID-19 Fears Questionnaire for Chronic Medical Conditions in Lithuania and to evaluate fears of COVID-19 in patients with pre-existing conditions. Between October and December, 2020, 371 respondents with pre-existing conditions completed an online survey including the 10-item COVID-19 Fears Questionnaire for Chronic Medical Conditions (COVID-19 fears), Patient Health Questionnaire-8 (PHQ-8; depressive symptoms), Generalised Anxiety Disorders-7 (GAD-7; anxiety symptoms) and Impact of Events Scale Revised (IES-R; posttraumatic stress symptoms). The majority of participants were women (84%) and from 41 to 60 years old (46%). The most common pre-existing conditions were respiratory diseases (33%) and diabetes (22%). Mean total score on the COVID-19 Fears Questionnaire was 24.89 ± 8.79. Exploratory factor analysis yielded one-factor solution with the Cronbach's coefficient alpha of 0.913. The highest rated COVID-19 fears were infection of close people, inability to receive treatment for COVID-19 and pre-existing condition and fear of severe complications because of the pre-existing condition. There was moderate to strong correlation of the 10-item COVID-19 Fears Questionnaire for Chronic Medical Conditions score with scores on the PHQ-8 (r = 0.371), GAD-7 (r = 0.358) and IES-R (r = 0.553; all p < 0.001). Test-retest reliability was adequate. The 10-item COVID-19 Fears Questionnaire for Chronic Medical Conditions has good psychometric properties in patients with pre-existing conditions and greater fear is associated with worse mental health. Consideration of COVID-19 fears is important for optimised care of patients with pre-existing during the pandemic.

Predictive value of baseline cognitive functioning on health-related quality of life in individuals with coronary artery disease: a 5-year longitudinal study.

AIMS: Emerging studies suggest an association exists between coronary artery disease (CAD) and the development of neurodegenerative diseases, with CAD acting as a precursor. Our study aimed to investigate the relationship between baseline measures of cognitive functioning and long-term health-related quality of life (HRQoL) in individuals with CAD with specification to Type D personality traits and sex. METHODS AND RESULTS: This prospective observational cohort study consisted of 864 participants (mean age 58 SD = 9 years, 74.0% men) with CAD after acute coronary syndrome. Baseline characteristics included comprehensive cognitive testing, measures of sociodemographic and clinical factors, and psychological assessment scales, such as Type D personality scale and the Hospital Anxiety and Depression scale. The Minnesota Living with Heart Failure Questionnaire assessed participants' HRQoL, conducted through phone interviews at baseline, every 6 months for up to 2 years, and after 5 years. Cognitive functioning correlated with HRQoL at all time intervals over the 5-year follow-up. Regarding sex and Type D personality, significant differences emerged in associations between impaired cognitive functioning at baseline and HRQoL measured over the period of 5 years. Men participants with characteristics of Type D personality were especially vulnerable to impaired cognitive functioning affecting the 5-year quality of life. CONCLUSION: Men with CAD who obtained scores indicating characteristics of Type D personality were significantly more likely to have lower baseline cognitive functions and long-term HRQoL outcomes. This information could inform healthcare practitioners to screen for personality characteristics and closely follow-up those at a greater risk.

Sonodynamic therapy for gliomas.

INTRODUCTION: Glioma remains incurable and a life limiting disease with an urgent need for effective therapies. Sonodynamic therapy (SDT) involves systemic delivery of non-toxic chemical agents (sonosensitizers) that accumulate in tumor cells or environment and are subsequently activated by exposure to low-frequency ultrasound to become cytotoxic agents. Herein, we discuss proposed mechanisms of action of SDT and provide recommendation for future research and clinical applications of SDT for gliomas. METHODS: Review of literature of SDT in glioma cell cultures and animal models published in Pubmed/MEDLINE before January, 2021. RESULTS: Different porphyrin and xanthene derivatives have proven to be effective sonosensitizers. Generation of reactive oxygen species and free radicals from water pyrolysis or sonosensitizers, or physical destabilization of cell membrane, have been identified as mechanisms of SDT leading to cell death. Numerous studies across glioma cell lines using various sonosensitizers and ultrasound parameters have documented tumoricidal effects of SDT. Studies in small animal glioma xenograft models have also consistently documented that SDT is associated with improved tumor control and longer survival of animals treated with SDT while avoiding damage of surrounding brain. There are no clinical trials completed to date regarding safety and efficacy of SDT in patients harboring gliomas, but some are beginning. CONCLUSIONS: Pre-clinical studies cell cultures and animal models indicate that SDT is a promising treatment approach for gliomas. Further studies should define optimal sonication parameters and sonosensitizers for gliomas. Clinical trials of SDT in patients harboring gliomas and other malignant brain tumors are currently underway.