New-generation oral anticoagulants for the prevention of stroke: Implications for neurosurgery

A new generation of oral anticoagulants, namely direct thrombin inhibitors and factor X_a inhibitors, have recently been approved for clinical use in patients with atrial fibrillation. These novel families of drugs have been shown to have favorable efficacy and safety profiles in multiple clinical settings, particularly in the prevention of atrial fibrillation-related stroke, and are likely to become part of everyday practice, making a crossover to neurosurgical patients inevitable. Concern has risen regarding the complexity of managing intracranial and intraspinal hemorrhages related to these drugs. This review aims to provide an update on the most recent advances in oral anticoagulant drug therapy from a neurosurgeon’s perspective. We discuss current evidence for the use of these novel agents, their limitations, existing methods of drug-level monitoring, and controversies related to anticoagulation reversal. We also discuss specific topics such as anticoagulation resumption after intracranial or intraspinal bleeding, perioperative anticoagulant administration, and the possibility of combination with tissue plasminogen activator in the setting of acute ischemic stroke. A special focus is given to the incidence of intracranial and intraspinal hemorrhage associated with each drug.     

Epidemiology of uncontrolled epilepsy in the Al-Kharga District,New Valley,Egypt

BackgroundDespite advances in treating epilepsy, uncontrolled epilepsy continues to be a major clinical problem. Therefore, this work aimed to study the epidemiology of uncontrolled epilepsy in Al-Kharga District, New Valley.MethodsThis study was carried out in 3 stages via door-to-door screening of the total population (62,583 persons). All suspected cases of epilepsy were subjected to case ascertainment, conventional ElectroEncephaloGraphy (EEG), and the Stanford-Binet Intelligence Scale. Patients who had been receiving suitable anti-epileptic drugs (AEDs) over the previous 6 months and were having active seizures were considered uncontrolled, according to Ohtsuka et al.²³ The patients underwent serum AED level estimation, video EEG monitoring, and brain MRIs. Fifty age- and gender-matched patients with controlled epilepsy were chosen for statistical analysis and compared with true intractable patients.ResultsA total of 437 patients with epilepsy were identified, 30.7% of whom (n = 134/437) were uncontrolled, with a prevalence of 2.1/1000. A total of 52.2% of uncontrolled patients (n = 70/134) were inappropriately treated, while 47.8% (n = 64/134) were compliant with appropriate treatments. Video monitoring EEG of compliant uncontrolled patients demonstrated that 78.1% patients (n = 50/64) had definite epilepsy, while 21.9% (n = 14/64) had psychogenic non-epileptic seizures (PNES). A logistic regression analysis revealed that status epilepticus, focal seizures, and mixed seizure types were risk factors for intractability.     

Frontotemporoparietal asymmetry and lack of illness awareness in schizophrenia

Introduction: Lack of illness awareness or anosognosia occurs in both schizophrenia and right hemisphere lesions due to stroke, dementia, and traumatic brain injury. In the latter conditions, anosognosia is thought to arise from unilateral hemispheric dysfunction or interhemispheric disequilibrium, which provides an anatomical model for exploring illness unawareness in other neuropsychiatric disorders, such as schizophrenia. Methods: Both voxel‐based morphometry using Diffeomorphic Anatomical Registration through Exponentiated Lie Algebra (DARTEL) and a deformation‐based morphology analysis of hemispheric asymmetry were performed on 52 treated schizophrenia subjects, exploring the relationship between illness awareness and gray matter volume. Analyses included age, gender, and total intracranial volume as covariates. Results: Hemispheric asymmetry analyses revealed illness unawareness was significantly associated with right < left hemisphere volumes in the anteroinferior temporal lobe (t = 4.83, P = 0.051) using DARTEL, and the dorsolateral prefrontal cortex (t = 5.80, P = 0.003) and parietal lobe (t = 4.3, P = 0.050) using the deformation‐based approach. Trend level associations were identified in the right medial prefrontal cortex (t = 4.49, P = 0.127) using DARTEL. Lack of illness awareness was also strongly associated with reduced total white matter volume (r = 0.401, P < 0.01) and illness severity (r = 0.559, P < 0.01). Conclusion: These results suggest a relationship between anosognosia and hemispheric asymmetry in schizophrenia, supporting previous volume‐based MRI studies in schizophrenia that found a relationship between illness unawareness and reduced right hemisphere gray matter volume. Functional imaging studies are required to examine the neural mechanisms contributing to these structural observations. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

The Current State of Teleradiology Across the United States: A National Survey of Radiologists’ Habits,Attitudes, and Perceptions on Teleradiology Practice

PurposeTo explore the current state of teleradiology practice, defined as the interpretation of imaging examinations at a different facility from where the examination was performed.MethodsA national survey addressing radiologists’ habits, attitudes, and perceptions regarding teleradiology was distributed by e-mail to a random sample of ACR members in early 2019.ResultsAmong 731 of 936 respondents who indicated a non-teleradiologist primary work setting, 85.6% reported performing teleradiology within the past 10 years and 25.4% reported that teleradiology represents a majority of their annual imaging volumes; 84.4% performed teleradiology for internal examinations and 45.7% for external examinations; 46.2% performed teleradiology for rural areas and 37.2% for critical access hospitals; 91.3% performed teleradiology during weekday normal business hours and 44.5% to 79.6% over evening, overnight, and weekend hours. In all, 76.9% to 86.2% perceived value from teleradiology for geographic, after-hours, and multispecialty coverage, as well as reduced interpretation turnaround times. The most common challenges for teleradiology were electronic health record access (62.8%), quality assurance (53.8%), and technologist proximity (48.4%). The strategy most commonly considered useful for improving teleradiology was technical interpretation standards (33.3%). Radiologists in smaller practices were less likely to perform teleradiology or performed teleradiology for lower fractions of work, were less likely to experience coverage advantages of teleradiology, and reported larger implementation challenges, particularly relating to electronic health records and prior examination access.ConclusionDespite historic concerns, teleradiology is widespread throughout modern radiology practice, helping practices achieve geographic, after-hours, and multispecialty coverage; reducing turnaround times; and expanding underserved access. Nonetheless, quality assurance of offsite examinations remains necessary. IT integration solutions could help smaller practices achieve teleradiology’s benefits.     

Incidental findings in emergency imaging: frequency,recommendations, and compliance with consensus guidelines

The purpose of this study was to evaluate the frequency of incidental findings (IFs) in emergency department (ED) imaging reports and evaluate the adherence of imaging recommendations to consensus societal guidelines for IFs. A retrospective review of consecutive ED computed tomography (CT) and ultrasonography (US) reports from two university-affiliated EDs over a 2-month period was performed. Each imaging report was reviewed in its entirety, and incidental findings were documented along with recommendations for additional imaging. Imaging recommendations were compared to published societal guidelines from the American College of Radiology (ACR) and Fleischner Society. Three thousand one hundred thirty-one total cases consisting of 1967 CTs and 1164 US contained 514 incidental findings (16.4 %), with 329 CT IFs (64 %) and 185 US IFs (36 %). The ovary was the most common organ for an IF (n?=?214, 42 %). Of all IFs, 347 (67.5 %) recommendations were concordant with societal guidelines and 167 (32.5 %) were discordant. 39.8 % of CT recommendations were discordant, while 19.5 % of US recommendations were discordant (p?<?0.0001). Incidental findings are commonly encountered in the emergent setting. Variable adherence to societal guidelines is noted. Targeted radiologist education and technological solutions may decrease rates of discordance.     

Impact of unilateral versus bilateral laparoscopic ovarian drilling on ovarian reserve and pregnancy rate: a randomized clinical trial

Objective: To assess the impact of unilateral dose adjusted ovarian drilling (ULOD) compared to bilateral ovarian drilling (BLOD) on ovarian reserve and pregnancy rate.

Methods: This randomized clinical study included 105 patients with polycystic ovary syndrome. Patients were assigned to two groups; group 1 (n?=?52) underwent dose adjusted ULOD using 60 Joules/cm³ applied to the larger ovary, while group 2 (n?=?53) underwent BLOD with fixed doses of 1200 J. Ovulation rate, anti-Mullerian hormone (AMH), antral follicle count (AFC), and pregnancy rates were assessed at 3 and 6 months of follow-up.

Results: Ovulation and pregnancy rates at 3 months periods were comparable (p?>?0.05), but was significantly higher in BLOD at 6 months period (p?p?p?>?0.05) but became higher in the ULOD at 6-month follow-up period (p?Conclusion: Dose-adjusted ULOD applied to the larger ovary has comparable ovulation and pregnancy rates to fixed dose BLOD at 3-month follow-up periods with decrease in its effectiveness after 6 months.     

Cisplatin-DNA damage in p21WAF1/Cip1 deficient mouse keratinocytes exposed to cisplatin

In response to DNA damage, cell cycle arrest, apoptosis, and DNA repair are mediated by a TP53 pathway that induces p21(WAF1/Cip1). The chemotherapeutic drug cis-diamminedichloroplatinum-II (cisplatin) damages cellular DNA by forming cis-diammineplatinum-N(7)-d[GpG] and cis-diammine-platinum-N(7)-d[ApG] adducts. To investigate the role of p21, skin keratinocytes from p21(WAF1/Cip1) wild-type (+/+), heterozygous (+/-), and null (-/-) mice, cultured in calcium levels designed to maintain a proliferating state, were exposed to 5 microM cisplatin continuously for 0, 8, 24, 48 and 72 h. At all time points the (+/-) cells had the fewest Pt-DNA adducts, and at 24 h mean Pt-DNA adduct levels were 541, 153 and 779 fmol adduct/mug DNA for p21(WAF1/Cip1) (+/+), (+/-) and (-/-) cells, respectively [P < 0.05 for (+/+) versus (+/-) and (-/-) versus (+/-)]. In order to understand underlying events, we examined p21(WAF1/Cip1) messenger RNA (mRNA), cell cycle arrest, and apoptosis in these cells. At 48 h of cisplatin exposure p21(WAF1/Cip1) mRNA expression was 2-fold higher in the (+/+) cells, compared to the (+/-) cells. At 24 h, the % of cells in S-phase in cisplatin-exposed cultures, compared to unexposed cultures, was decreased by 51, 40 and 11% in p21(WAF1/Cip1) (+/+), (+/-) and (-/-) cells, respectively (P = 0.04, ANOVA). At 24, 48 and 72 h the % of cisplatin-exposed (+/+) cells in apoptosis was 9.4-10.5%, while the cisplatin-exposed (+/-) and (-/-) cells had 1.2-3.7% of cells in apoptosis. The data support the interpretation that DNA replication arrest and apoptosis do not completely explain the low levels of Pt-DNA adducts in the (+/-) cells, and suggest that p21(WAF1/Cip1) controls activity resulting in either low Pt-DNA adduct formation or enhanced Pt-DNA adduct removal.     

Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children

CD31(+)CD45RA(+)RO(-) lymphocytes contain high numbers of T cell receptor circle (TREC)-bearing T cells; however, the correlation between CD31(+)CD4(+) lymphocytes and TREC during aging and under lymphopenic conditions has not yet been sufficiently investigated. We analyzed TREC, telomere length and telomerase activity within sorted CD31(+) and CD31(-) CD4(+) lymphocytes in healthy individuals from birth to old age. Sorted CD31(+)CD45RA(+)RO(-) naive CD4(+) lymphocytes contained high TREC numbers, whereas CD31(+)CD45RA(-)RO(+) cells (comprising < or =5% of CD4(+) cells during aging) did not contain TREC. CD31(+) overall CD4(+) cells remained TREC rich despite an age-related tenfold reduction from neonatal (100 : 1000) to old age (10 : 1000). Besides a high TREC content, CD31(+)CD45RA(+)RO(-)CD4(+) cells exhibited significantly longer telomeres and higher telomerase activity than CD31(-)CD45RA(+)RO(-)CD4(+) cells, suggesting that CD31(+)CD45RA(+)RO(-)CD4(+) cells represent a distinct population of naive T cells with particularly low replicative history. To analyze the value of CD31 in lymphopenic conditions, we investigated six children after allogeneic hematopoietic stem cell transplantation (HSCT). Reemerging overall CD4(+) as well as naive CD45RA(+)RO(-)CD4(+) cells predominantly expressed CD31 and correlated well with the recurrence of TREC 5-12 months after HSCT. Irrespective of limitations in the elderly, CD31 is an appropriate marker to monitor TREC-rich lymphocytes essentially in lymphopenic children after HSCT.