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.

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.

The impact of pre-existing conditions and perceived health status on mental health during the COVID-19 pandemic.

BACKGROUND: Patients with pre-existing conditions and poor health status are vulnerable for adverse health sequalae during the COVID-19 pandemic. We investigated the association of pre-existing medical conditions and self-perceived health status with the risk of mental health complications during the COVID-19 pandemic. METHODS: In October-December, 2020, 1036 respondents completed online survey that included assessment of pre-existing conditions, self-perceived health status, depressive (Patient Health Questionnaire-8 score ≥ 10), anxiety (Generalized Anxiety Disorders-7 score ≥ 10) and post-traumatic stress (Impact of Events Scale Revised) symptoms, alcohol use (AUDIT), and COVID-19 fear (COVID-19 Fears Questionnaires for Chronic Medical Conditions). RESULTS: Study participants were predominantly women (83%), younger than 61 years of age (94%). Thirty-six percent of respondents had a pre-existing condition and 5% considered their health status as bad or very bad. Pre-existing conditions and poor perceived health status were associated with increased risk for moderate to severe depressive and anxiety symptoms, fear of COVID-19 and post-traumatic stress symptoms, independently from respondents' age, gender, living area, smoking status, exercise, alcohol consumption and diet. CONCLUSIONS: Pre-existing medical conditions and poor perceived health status are associated with increased risk of poor mental health status during the COVID-19 pandemic.

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.

Stereotactic radiosurgery for asymptomatic petroclival region meningiomas: a focused analysis from the IMPASSE study.

BACKGROUND: The optimal management of asymptomatic, petroclival meningiomas remains incompletely defined. The purpose of this study was to evaluate the safety and efficacy of upfront stereotactic radiosurgery (SRS) for patients with asymptomatic, petroclival region meningiomas. METHODS: This retrospective, international, multicenter study involved patients treated with SRS for an asymptomatic, petroclival region meningioma. Study endpoints included local tumor control rate, procedural complications, and the emergence of new neurological deficits. RESULTS: There were 72 patients (22 males, mean age 59.53 years (SD ± 11.9)) with an asymptomatic meningioma located in the petroclival region who were treated with upfront SRS. Mean margin dose and maximum dose were 13.26 (SD ± 2.72) Gy and 26.14 (SD ± 6.75) Gy respectively. Median radiological and clinical follow-up periods post-SRS were 52.5 (IQR 61.75) and 47.5 months (IQR 69.75) respectively. At last follow-up, tumor control was achieved in all patients. SRS-related complications occurred in 6 (8.33%) patients, with 3 of them (4.17%) exhibiting new neurological deficits. CONCLUSIONS: Upfront SRS for asymptomatic, petroclival region meningiomas affords excellent local tumor control and does so with a relatively low risk of SRS-related complications. SRS can be considered at diagnosis of an asymptomatic petroclival region meningioma. If active surveillance is initially chosen, SRS should be recommended when growth is noted during radiological follow-up.

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.

Stereotactic radiosurgery for IDH wild type glioblastoma: an international, multicenter study.

OBJECTIVE: Isocitrate dehydrogenase (IDH) mutation status is recommended used for diagnosis and prognostication of glioblastoma patients. We studied efficacy and safety of stereotactic radiosurgery (SRS) for patients with recurrent IDH-wt glioblastoma. METHODS: Consecutive patients treated with SRS for IDH-wt glioblastoma were pooled for this retrospective observational international multi-institutional study from institutions participating in the International Radiosurgery Research Foundation. RESULTS: Sixty patients (median age 61 years) underwent SRS (median dose 15 Gy and median treatment volume: 7.01 cm3) for IDH-wt glioblastoma. All patients had histories of surgery and chemotherapy with temozolomide, and 98% underwent fractionated radiation therapy. MGMT status was available for 42 patients, of which half of patients had MGMT mutant glioblastomas. During median post-SRS imaging follow-up of 6 months, 52% of patients experienced tumor progression. Median post-SRS progression free survival was 4 months. SRS prescription dose of > 14 Gy predicted longer progression free survival [HR 0.357 95% (0.164-0.777) p = 0.009]. Fifty-percent of patients died during post-SRS clinical follow-up that ranged from 1 to 33 months. SRS treatment volume of > 5 cc emerged as an independent predictor of shorter post-SRS overall survival [HR 2.802 95% CI (1.219-6.444) p = 0.02]. Adverse radiation events (ARE) suggestive of radiation necrosis were diagnosed in 6/55 (10%) patients and were managed conservatively in the majority of patients. CONCLUSIONS: SRS prescription dose of > 14 Gy is associated with longer progression free survival while tumor volume of > 5 cc is associated with shorter overall survival after SRS for IDH-wt glioblastomas. AREs are rare and are typically managed conservatively.

Internal carotid artery stenosis and risk of cerebrovascular ischemia following stereotactic radiosurgery for recurrent or residual pituitary adenomas.

PURPOSE: To evaluate the incidence of internal carotid artery (ICA) stenosis and cerebrovascular accident in a series of patients treated with stereotactic radiosurgery (SRS) for recurrent or residual pituitary adenoma. METHODS: All patients treated with single fraction SRS in our institution for recurrent or residual non-functioning-, growth hormone- and ACTH-secreting pituitary adenomas were retrospectively identified and reviewed. A comprehensive literature review to identify studies reporting on ICA steno-occlusive disease following SRS for pituitary adenomas and compare the risks of carotid stenosis and ischemic stroke in the SRS treated group to the general population figures. RESULTS: 528 patients [312 women and 216 men; median age at SRS 46 years old (range 12-80 years)] treated with SRS at our institution met study inclusion criteria. Mean clinical and radiologic follow-ups were 68.87 (SD ± 43.29) and 55.99 months (SD ± 38.03), respectively, and there were no clinically evident cerebral ischemic events noted. Asymptomatic, post-SRS, ICA stenosis occurred in two patients. A total of eight patients with ICA steno-occlusive disease following pituitary adenoma radiosurgery have been reported. Two of them suffered from ischemic stroke with however excellent recovery. CONCLUSION: As compared to the general population, SRS for pituitary adenomas does not seem to confer appreciable increased risk for ICA steno-occlusive disease and ischemic stroke. However, post-SRS radiation vessel injuries do occur and physicians should be aware about this rare event. Prompt identification and management according to current guidelines are essential to prevent ischemic strokes.

Multidimensional Structure of the Alcohol Use Disorders Identification Test: Factorial Validity and Reliability in Patients With Anxiety and Mood Disorders in Lithuania.

AIMS: The current study aimed to evaluate the factorial structure of the Lithuanian version of the Alcohol Use Disorders Identification Test (AUDIT) in patients with anxiety and mood disorders (AMD). METHODS: The AUDIT was completed by 199 consecutive outpatients with AMD (21% men, mean age 39 ± 12 years), as defined by AMD criteria in DSM-5. The MINI International Neuropsychiatric Interview was used for current diagnosis of alcohol use disorder (AUD). Sociodemographic and clinical data were also collected. RESULTS: In patients with AMD, the AUDIT showed high internal consistency (Cronbach's alpha = 0.88) and good psychometric characteristics for identifying current AUD at a cut-off value of ≥9 (positive predictive value = 83.7%, sensitivity = 94.7%, specificity = 95.7%). The confirmatory factor analysis suggested a three-factor ('consumption', 'dependence' and 'related consequences') structure and indicated adequate fit to the model (comparative fit index = 0.966, normed fit index = 0.936, root mean square error of approximation = 0.072). CONCLUSIONS: The findings are in line with increasing evidence suggesting that the AUDIT measures three separate factors related to alcohol misuse level of consumption, dependence and alcohol-related consequences and support the utility of AUDIT as a screening instrument for AUD in AMD patients in Lithuania.

Endoscopic third ventriculostomy versus ventriculoperitoneal shunt in pediatric and adult population: a systematic review and meta-analysis.

Treatment options for hydrocephalus include endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS). Some ambiguity remains regarding indications, safety, and efficacy for these procedures in different clinical scenarios. The objective of the present study was to pool the available evidence to compare outcomes among patients with hydrocephalus undergoing ETV versus VPS. A systematic search of the literature was conducted via PubMed, EMBASE, and Cochrane Library through 11/29/2018 to identify studies evaluating failure and complication rates, following ETV or VPS. Pooled effect estimates were calculated using random effects. Heterogeneity was assessed by the Cochrane Q test and the I2 value. Heterogeneity sources were explored through subgroup analyses and meta-regression. Twenty-three studies (five randomized control trials (RCTs) and 18 observational studies) were meta-analyzed. Comparing ETV to VPS, failure rate was not statistically significantly different with a pooled relative risk (RR) of 1.48, 95%CI (0.85, 2.59) for RCTs and 1.17 (0.89, 1.53) for cohort studies; P-interaction: 0.44. Complication rates were not statistically significantly different between ETV and VPS in RCTs (RR: 1.34, 95%CI: 0.50, 3.59) but were statistically significant for prospective cohort studies (RR: 0.47, 95%CI: 0.30, 0.78); P-interaction: 0.07. Length of hospital stay was no different, when comparing ETV and VPS. These results remained unchanged when stratifying by intervention type and when regressing on age when possible. No significant differences in failure rate were observed between ETV and VPS. ETV was found to have lower complication rates than VPS in prospective cohort studies but not in RCTs. Further research is needed to identify the specific patient populations who may be better suited for one intervention versus another.

Safety and efficacy of prothrombin complex concentrate (PCC) for anticoagulation reversal in patients undergoing urgent neurosurgical procedures: a systematic review and metaanalysis.

Anticoagulant therapy poses a significant risk for patients undergoing emergency neurosurgery procedures, necessitating reversal with prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP). Data on PCC efficacy lack consistency in this setting. This systematic review and metaanalysis aimed to evaluate efficacy and safety of PCC for anticoagulation reversal in the context of urgent neurosurgery. Articles from PubMed, Embase, and Cochrane databases were screened according to the PRISMA checklist. Adult patients receiving anticoagulation reversal with PCC for emergency neurosurgical procedures were included. When available, patients who received FFP were included as a comparison group. Pooled estimates of observational studies were calculated for efficacy and safety outcomes via random-effects modeling. Initial search returned 4505 articles, of which 15 studies met the inclusion criteria. Anticoagulants used included warfarin (83%), rivaroxaban (6.8%), phenprocoumon (6.1%), apixaban (2.2%), and dabigatran (1.5%). The mean International Normalized Ratio (INR) prePCC administration ranged from 2.3 to 11.7, while postPCC administration from 1.1 to 1.4. All-cause mortality at 30 days was 27% (95%CI 21, 34%; I2 = 44.6%; p-heterogeneity = 0.03) and incidence of thromboembolic events was 6.00% among patients treated with PCC (95%CI 4.00, 10.0%; I2 = 0%; p-heterogeneity = 0.83). Results comparing PCC and FFP demonstrated no statistically significant differences in INR reversal, mortality, or incidence of thromboembolic events. This metaanalysis demonstrated adequate safety and efficacy for PCC in the reversal of anticoagulation for urgent neurosurgical procedures. There was no significant difference between PCC and FFP, though further trials would be useful in demonstrating the safety and efficacy of PCC in this setting.

Outcomes from treatment of asymptomatic skull base meningioma with stereotactic radiosurgery.

BACKGROUND: Optimal management of asymptomatic skull base meningiomas is controversial. We evaluated the safety and efficiency of Gamma Knife radiosurgery (GKRS) for the management of asymptomatic skull base meningiomas. METHODS: This retrospective study involved patients managed with GKRS for asymptomatic, skull base meningiomas from 1997 to 2019. Patient clinico-radiologic data, tumor characteristics, and procedural details were analyzed. Favorable outcome was defined as lack of procedure-related mortality or permanent neurologic morbidity and radiologic evidence of tumor control. Tumor progression and regression were defined as an increase or decrease of > 20% in volume from baseline to the last neuroimaging study respectively. Tumor volumes within ± 20% of baseline volume were considered stable. RESULTS: Thirty-seven patients (30 women), median age 68 years old (range 42-83 months) were managed with a single-session GKRS for 40 asymptomatic, skull base meningiomas. At a median clinical follow-up of 58.5 months (range 14-150 months), no mortality associated with the procedure or the treated tumor was noted. Permanent neurologic morbidity was 2.75%. There was a statistically significant decrease in mean tumor volume (p < 0.001) from 4.04 cc (SD 3.09 cc) prior to radiosurgery to 2.73 cc (SD 2.24 cc) at last follow-up. Higher margin dose was associated with tumor regression at last follow-up (HR = 1.351; 95%CI [1.094-1.669]; p = 0.05). CONCLUSION: As compared to natural history studies, GKRS affords long-standing tumor control and neurologic preservation in the vast majority of patients treated for asymptomatic, skull base meningiomas. Further study is necessary to identify the optimal management of asymptomatic skull base meningiomas.

Stereotactic radiosurgery before bilateral adrenalectomy is associated with lowered risk of Nelson's syndrome in refractory Cushing's disease patients.

BACKGROUND: Nelson's syndrome is a rare but challenging sequelae of Cushing's disease (CD) after bilateral adrenalectomy (BLA). We sought to determine if stereotactic radiosurgery (SRS) of residual pituitary adenoma performed before BLA can decrease the risk of Nelson's syndrome. METHODS: Consecutive patients with CD who underwent BLA after non-curative resection of ACTH secreting pituitary adenoma and had at least one follow-up visit after BLA were studied. Nelson's syndrome was diagnosed based on the combination of rising ACTH levels, increasing volume of the pituitary adenoma and/or hyperpigmentation. RESULTS: Fifty patients underwent BLA for refractory CD, and 43 patients (7 men and 36 women) had at least one follow-up visit after BAL. Median endocrine, imaging, and clinical follow-up were 66 months, 69 months, and 80 months, respectively. Nine patients (22%) were diagnosed with the Nelson's syndrome at median time after BLA at 24 months (range: 0.6-119.4 months). SRS before BLA was associated with reduced risk of the Nelson's syndrome (HR = 0.126; 95%CI [0.022-0.714], p=0.019), while elevated ACTH level within 6 months after BLA was associated with increased risk for the Nelson's syndrome (HR = 9.053; 95%CI [2.076-39.472], p=0.003). CONCLUSIONS: SRS before BLA can reduce the risk for the Nelson's syndrome in refractory CD patients requiring BLA and should be considered before proceeding to BLA. Elevated ACTH concentration within 6 months after BLA is associated with greater risk of the Nelsons' syndrome. When no prior SRS is administered, those with a high ACTH level shortly after BLA may benefit from early SRS.

Stereotactic radiosurgery for clinoid meningiomas: a multi-institutional study.

PURPOSE: Resection of clinoid meningiomas can be associated with significant morbidity. Experience with stereotactic radiosurgery (SRS) for clinoid meningiomas remains limited. We studied the safety and effectiveness of SRS for clinoid meningiomas. METHODS: From twelve institutions participating in the International Radiosurgery Research Foundation, we pooled patients treated with SRS for radiologically suspected or histologically confirmed WHO grade I clinoid meningiomas. RESULTS: Two hundred seven patients (median age: 56 years) underwent SRS for clinoid meningiomas. Median treatment volume was 8.02 cm3, and 87% of tumors were immediately adjacent to the optic apparatus. The median tumor prescription dose was 12 Gy, and the median maximal dose to the anterior optic apparatus was 8.5 Gy. During a median post-SRS imaging follow-up of 51.1 months, 7% of patients experienced tumor progression. Greater margin SRS dose (HR = 0.700, p = 0.007) and pre-SRS radiotherapy (HR = 0.004, p < 0.001) were independent predictors of better tumor control. During median visual follow-up of 48 months, visual function declined in 8% of patients. Pre-SRS visual deficit (HR = 2.938, p = 0.048) and maximal radiation dose to the optic apparatus of ≥ 10 Gy (HR = 11.297, p = 0.02) independently predicted greater risk of post-SRS visual decline. Four patients experienced new post-SRS cranial nerve V neuropathy. CONCLUSIONS: SRS allows durable control of clinoid meningiomas and visual preservation in the majority of patients. Greater radiosurgical prescription dose is associated with better tumor control. Radiation dose to the optic apparatus of ≥ 10 Gy and visual impairment before the SRS increase risk of visual deterioration.

Isocitrate Dehydrogenase, Patient-Reported Outcomes, and Cognitive Functioning of Glioma Patients: a Systematic Review.

PURPOSE OF REVIEW: Isocitrate dehydrogenase (IDH) mutation status has important prognostic implications in glioma patients, with IDH wild-type (IDH-WT) gliomas being associated with worse prognosis and shorter survival when compared with IDH mutant (IDH-mut) gliomas. Optimization of quality of life is a priority in the management of glioma patients. The goal of this systematic review was to identify studies that explored the association of IDH mutation status with patient-reported outcomes (PROs) and cognitive functioning of glioma patients. RECENT FINDINGS: Studies that evaluated the association of IDH mutation status with PROs and/or cognitive functioning of glioma patients were identified from the Pubmed/MEDLINE, Clarivate analytics, and Google Scholar databases. Eight studies (7 journal articles and 2 conference abstracts) with a total of 658 low-grade glioma and high-grade glioma patients investigated the association of cognitive functioning and/or QoL with IDH status. IDH-WT status was associated with greater cognitive impairment relative to IDH-Mut status in three studies, while one study did not find the association between IDH status and perioperative cognitive functioning. One study reported worse postoperative cognitive functioning patients with IDH-WT vs. IDH-mut gliomas. In one study, IDH-WT status was linked to greater impairment on physical and communication functioning after surgery. IDH-WT gliomas are associated with greater cognitive burden than IDH-Mut tumors. The association of IDH status with QoL remains less clear. Assessment of IDH status should be considered when evaluating QoL and cognitive complaints of glioma patients. Further studies linking glioma molecular phenotypes with PROs and cognitive functioning are encouraged.

Validation of the Substance Use Risk Profile Scale in Lithuanian population.

BACKGROUND: Personality traits are related with risk of hazardous alcohol use and alcohol dependence. The Substance Use Risk Profile Scale (SURPS) measures personality traits associated with addictive substance abuse. We examined psychometric properties of the SURPS in Lithuanian population. MATERIALS AND METHODS: Two hundred forty-seven participants (mean age 37.22 ± 0.78 years), were recruited from the local community and from an inpatient addiction treatment centre. Internal consistency, stability, factor structure, content validity, and external validity of the SURPS were examined. Hazardous alcohol use was evaluated by Alcohol Use Disorder Identification Test (AUDIT). Alcohol dependence diagnosis was established by International Classification of Diseases - 10 (ICD - 10). We also performed gender analyses for associations of personality traits with alcohol dependence and hazardous use of alcohol. RESULTS: The SURPS scale demonstrated appropriate internal validity, good temporal stability, and adequate criterion validity and construct validity. The SURPS scores of hopelessness, anxiety sensitivity and impulsivity were higher in the alcohol dependence group than in the control group for both males and females. Impulsivity and sensation seeking were associated with hazardous alcohol use and these associations were more prevalent in females. CONCLUSIONS: Lithuanian translation of the SURPS scale was appropriate. The SURPS demonstrated good sensitivity for discriminating on alcohol dependence and was more sensitive for discriminating on hazardous alcohol use for females.

Unique Interplay Between Molecular miR-181b/d Biomarkers and Health Related Quality of Life Score in the Predictive Glioma Models.

In the last decade, an increasing amount of research has been conducted analyzing microRNA expression changes in glioma tissue and its expressed exosomes, but there is still sparse information on microRNAs or other biomarkers and their association with patients' functional/psychological outcomes. In this study, we performed a combinational analysis measuring miR-181b and miR-181d expression levels by quantitative polymerase chain reaction (qPCR), evaluating isocitrate dehydrogenase 1 (IDH1) single nucleotide polymorphism (SNP), and O-6-methylguanine methyltransferase (MGMT) promoter methylation status in 92 post-surgical glioma samples and 64 serum exosomes, including patients' quality of life evaluation applying European Organization for Research and Treatment of Cancer (EORTC) questionnaire for cancer patients (QLQ-30), EORTC the Brain Cancer-Specific Quality of Life Questionnaire (QLQ-BN20), and the Karnofsky performance status (KPS). The tumoral expression of miR-181b was lower in grade III and glioblastoma, compared to grade II glioma patients (p < 0.05). Additionally, for the first time, we demonstrated the association between miR-181 expression levels and patients' quality of life. A positive correlation was observed between tumoral miR-181d levels and glioma patients' functional parameters (p < 0.05), whereas increased exosomal miR-181b levels indicated a worse functional outcome (p < 0.05). Moreover, elevated miR-181b exosomal expression can indicate a significantly shorter post-surgical survival time for glioblastoma multiforme (GBM) patients. In addition, both tumoral and exosomal miR-181 expression levels were related to patients' functioning and tumor-related symptoms. Our study adds to previous findings by demonstrating the unique interplay between molecular miR-181b/d biomarkers and health related quality of life (HRQOL) score as both variables remained significant in the predictive glioma models.

Maternal cognitive function during pregnancy in relation to hypo- and hyperthyroxinemia.

OBJECTIVE: To assess a possible relationship between maternal cognitive dysfunction during pregnancy and hypothyroxinemia, adjusted for major confounders. BACKGROUND: Thyroid dysfunction in general is associated with cognitive dysfunction. Cognitive dysfunction is common during pregnancy. DESIGN: Prospective follow-up study from 12 to 32 weeks of pregnancy. PARTICIPANTS: 2082 healthy pregnant women. MEASUREMENTS: Cognitive function, depression and sleeping problems were assessed by self-report questionnaires at 12, 22 and 32 weeks of gestation, higher scores reflecting more symptoms. FT4, TSH and TPO-Ab were assessed at 12 weeks of gestation. DEFINITIONS: healthy (euthyroxinemia) control group: FT4 within 10-90th percentiles, without elevated TPO-Ab titres and TSH within first trimester-specific reference range (0.23-4.0 mU/L). Hypothyroxinemia: FT4 <2.5th percentile with TSH within first trimester-specific reference range. Poor cognitive function: a score >1 SD > mean on the cognitive function scale. RESULTS: A total of 54 women showed hypothyroxinemia and 1476 women had euthyroxinemia. At 12 weeks, multiple logistic regression showed that poor cognitive function was independently related to hypothyroxinemia: OR: 2.9 (95% CI: 1.6-5.4), adjusted for depression (OR: 3.1; 95% CI: 2.7-4.6) and sleeping problems (OR: 2.8, 95% CI: 1.9-3.9). TPO-Ab + women with hypothyroxinemia had the highest levels of cognitive dysfunction. Other cut-offs of hypothyroxinemia (<5th or <10th percentile with normal TSH) showed similar results. GLM-ANOVA showed that throughout pregnancy women with hypothyroxinemia at 12 weeks had significantly higher cognitive dysfunction scores compared with the healthy controls: F = 12.1, P = .001. CONCLUSIONS: Women with hypothyroxinemia during early gestation are at risk for poor cognitive function throughout gestation, adjusted for depression and sleeping problems.

Surgical and radiosurgical treatment strategies for Cushing's disease.

INTRODUCTION: Cushing's disease (CD) is rare disorder that should be adequately managed to optimize long-term prognosis. Treatment of CD is multidisciplinary and often includes surgical resection, adjuvant stereotactic radiosurgery (SRS), and medical treatment. Here we review surgical and radiosurgical treatment strategies for ACTH producing pituitary adenomas. METHODS: A comprehensive literature review was carried out to review remission and recurrence rates, and complications of surgical and SRS treatments of ACTH producing pituitary adenomas. RESULTS: Surgical resection plays a central role in the management of ACTH secreting pituitary adenomas and usually allows rapid endocrine remission that ranges from 69 to 90%. The most common complications after resection include some degree of new hypopituitarism, diabetes insipidus and CSF leak. Devastating complications, such as injury of vascular and neural structures, are very rare. Surgeon experience and adequate pre-operative imaging are important for safe and successful surgery. Endocrine recurrence rates after resection range from 9 to 30%. SRS is often employed for incompletely resected adenomas. Endocrine remission after SRS ranges from 35 to 72%. The most common complication of SRS is new anterior pituitary gland deficiency. Recurrence rates after GKRS range from 18 to 24%. CONCLUSIONS: Transsphenoidal resection of ACTH producing pituitary adenoma is a safe and highly effective procedure for CD in experienced hands. Radiosurgery is more frequently used as treatment of residual and recurrent adenoma and persistent CD. Long-term endocrine and imaging follow-up is important as delayed recurrences and hypopituitarism are not infrequent.