Traumatic Cerebral Microbleeds in the Subacute Phase Are Practical and Early Predictors of Abnormality of the Normal-Appearing White Matter in the Chronic Phase

BACKGROUND AND PURPOSE:In the chronic phase after traumatic brain injury, DTI findings reflect WM integrity. DTI interpretation in the subacute phase is less straightforward. Microbleed evaluation with SWI is straightforward in both phases. We evaluated whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase.MATERIALS AND METHODS:Sixty of 211 consecutive patients 18 years of age or older admitted to our emergency department ≤24 hours after moderate to severe traumatic brain injury matched the selection criteria. Standardized 3T SWI, DTI, and T1WI were obtained 3 and 26 weeks after traumatic brain injury in 31 patients and 24 healthy volunteers. At baseline, microbleed concentrations were calculated. At follow-up, mean diffusivity (MD) was calculated in the normal-appearing WM in reference to the healthy volunteers (MD_z). Through linear regression, we evaluated the relation between microbleed concentration and MD_z in predefined structures.RESULTS:In the cerebral hemispheres, MD_z at follow-up was independently associated with the microbleed concentration at baseline (left: B = 38.4 [95% CI 7.5–69.3], P = .017; right: B = 26.3 [95% CI 5.7–47.0], P = .014). No such relation was demonstrated in the central brain. MD_z in the corpus callosum was independently associated with the microbleed concentration in the structures connected by WM tracts running through the corpus callosum (B = 20.0 [95% CI 24.8–75.2], P < .000). MD_z in the central brain was independently associated with the microbleed concentration in the cerebral hemispheres (B = 25.7 [95% CI 3.9–47.5], P = .023).CONCLUSIONS:SWI-assessed microbleeds in the subacute phase are associated with DTI-based WM integrity in the chronic phase. These associations are found both within regions and between functionally connected regions.

The yearly incidence of traumatic brain injury (TBI) is around 300 per 100,000 persons.^1,2 Almost three-quarters of patients with moderate to severe TBI have traumatic axonal injury (TAI).³ TAI is a major predictor of functional outcome,^4,5 but it is mostly invisible on CT and conventional MR imaging.^6,7DTI provides direct information on WM integrity and axonal injury.^5,8 However, DTI abnormalities are neither specific for TAI nor stable over time. Possibly because of the release of mass effect and edema and resorption of blood products, the effects of concomitant (non-TAI) injury on DTI are larger in the subacute than in the chronic phase (>3 months).^4,9,10 Therefore, DTI findings are expected to reflect TAI more specifically in the chronic than in the subacute phase (1 week–3 months).⁴ Even in regions without concomitant injury, the effects of TAI on DTI are dynamic, possibly caused by degeneration and neuroplastic changes.^6,11,12 These ongoing pathophysiological processes possibly contribute to the emerging evidence that DTI findings in the chronic phase are most closely associated with the eventual functional outcome.^12,13Although DTI provides valuable information, its acquisition, postprocessing, and interpretation in individual patients are demanding. SWI, with which microbleeds can be assessed with high sensitivity, is easier to interpret and implement in clinical practice. In contrast to DTI, SWI-detected traumatic microbleeds are more stable¹ except in the hyperacute^14,15 and the late chronic phases.¹⁶ Traumatic cerebral microbleeds are commonly interpreted as signs of TAI. However, the relation is not straightforward. On the one hand, nontraumatic microbleeds may be pre-existing. On the other hand, even if traumatic in origin, microbleeds represent traumatic vascular rather than axonal injury.¹⁷ Indeed, TAI is not invariably hemorrhagic.¹⁸ Additionally, microbleeds may secondarily develop after trauma through mechanisms unrelated to axonal injury, such as secondary ischemia.¹⁸DTI is not only affected by pathophysiological changes but also by susceptibility.¹⁹ The important susceptibility-effect generated by microbleeds renders the interpretation of DTI findings at the location of microbleeds complex. In the chronic phase, mean diffusivity (MD) is the most robust marker of WM integrity.^4,6 For these reasons, we evaluated MD in the normal-appearing WM.Much TAI research focuses on the corpus callosum because it is commonly involved in TAI^5,18,20 and it can reliably be evaluated with DTI,^5,21 and TAI in the corpus callosum is related to clinical prognosis.^6,20 The corpus callosum consists of densely packed WM tracts that structurally and functionally connect left- and right-sided brain structures.²² The integrity of the corpus callosum is associated with the integrity of the brain structures it connects.²³ Therefore, microbleeds in brain structures that are connected through the corpus callosum may affect callosal DTI findings. Analogous to this, microbleeds in the cerebral hemispheres, which exert their function through WM tracts traveling through the deep brain structures and brain stem,^24,25 may affect DTI findings in the WM of the latter.Our purpose was to evaluate whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase. We investigated this relation within the cerebral hemispheres and the central brain and between regions that are functionally connected by WM tracts.     

Trans-Pacific tele-ultrasound image transmission of fetal central nervous system structures

Objective: To assess the quality of images and video clips of fetal central nervous (CNS) structures obtained by ultrasound and transmitted via tele-ultrasound from Brazil to Australia.

Methods: In this cross-sectional study, 15 normal singleton pregnant women between 20 and 26 weeks were selected. Fetal CNS structures were obtained by images and video clips. The exams were transmitted in real-time using a broadband internet and an inexpensive video streaming device. Four blinded examiners evaluated the quality of the exams using the Likert scale. We calculated the mean, standard deviation, mean difference, and p values were obtained from paired t tests.

Results: The quality of the original video clips was slightly better than that observed by the transmitted video clips; mean difference considering all observers = 0.23 points. In 47/60 comparisons (78.3%; 95% CI?=?66.4–86.9%) the quality of the video clips were judged to be the same. In 182/240 still images (75.8%; 95% CI?=?70.0–80.8%) the scores of transmitted image were considered the same as the original.

Conclusion: We demonstrated that long distance tele-ultrasound transmission of fetal CNS structures using an inexpensive video streaming device provided images of subjective good quality.     

Ospemifene plus fractional CO2 laser: a powerful strategy to treat postmenopausal vulvar pain

Abstract

This study is a single-center, retrospective analysis of postmenopausal women presenting with dyspareunia and vulvar pain, aiming to evaluate relative effectiveness of vestibular CO₂ laser therapy as a treatment. Three monthly sessions of laser were performed to each patient and thereafter a three-months follow-up was stablished. A total number of 72 patients undergoing vestibular laser treatment were recruited from patient files in the period between 2016 and 2018. Among these, 39 women also received a concomitant treatment with ospemifene (60?mg/day) during the study period. There was a statistically significant reduction of all the symptoms in both groups up to the three month follow-up. Regarding dryness and dyspareunia, the relief tent to be more prominent in the ospemifene?+?laser group at all follow-ups and remained statistically significant at three-month follow-up. Specifically, vestibular dryness was significantly lower in the ospemifene?+?laser group compared with the laser treatment group (?87% vs???34%, respectively), and the vestibular health score started declining faster in the ospemifene?+?laser group. Although, additional research is needed to understand the mechanism of action, our data shows that a combination regimen of laser and ospemifene may improve clinical effectiveness for long-term treatment of symptoms associated with the under-recognized genitourinary syndrome of menopause.     

Are Medicare's Nursing Home Compare Ratings Accurate Predictors of 90-Day Complications,Readmission, and Bundle Cost for Patients Undergoing Primary Total Joint Arthroplasty?

Background

Nursing Home Compare (NHC) ratings, created and maintained by Medicare, are used by both hospitals and consumers to aid in the skilled nursing facility (SNF) selection process. To date, no studies have linked NHC ratings to actual episode-based outcomes. The purpose of this study was to evaluate whether NHC ratings are valid predictors of 90-day complications, readmission, and bundle costs for patients discharged to an SNF after primary total joint arthroplasty (TJA).

Priming sentence comprehension in aphasia: effects of lexically independent and specific structural priming

Background & Aims: Impaired message-structure mapping results in deficits in both sentence production and comprehension in aphasia. Structural priming has been shown to facilitate syntactic production for persons with aphasia (PWA). However, it remains unknown if structural priming is also effective in sentence comprehension. We examined if PWA show preserved and lasting structural priming effects during interpretation of syntactically ambiguous sentences and if the priming effects occur independently of or in conjunction with lexical (verb) information.

Methods & Procedures: Eighteen PWA and 20 healthy older adults (HOA) completed a written sentence-picture matching task involving the interpretation of prepositional phrases (PP; the chef is poking the solider with an umbrella) that were ambiguous between high (verb modifier) and low attachment (object noun modifier). Only one interpretation was possible for prime sentences, while both interpretations were possible for target sentences. In Experiment 1, the target was presented immediately after the prime (0-lag). In Experiment 2, two filler items intervened between the prime and the target (2-lag). Within each experiment, the verb was repeated for half of the prime-target pairs, while different verbs were used for the other half. Participants’ off-line picture matching choices and response times were measured.

Results: After reading a prime sentence with a particular interpretation, HOA and PWA tended to interpret an ambiguous PP in a target sentence in the same way and with faster response times. Importantly, both groups continued to show this priming effect over a lag (Experiment 2), although the effect was not as reliable in response times. However, neither group showed lexical (verb-specific) boost on priming, deviating from robust lexical boost seen in the young adults of prior studies.

Conclusions: PWA demonstrate abstract (lexically-independent) structural priming in the absence of a lexically-specific boost. Abstract priming is preserved in aphasia, effectively facilitating not only immediate but also longer-lasting structure-message mapping during sentence comprehension.     

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen

Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.

Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.

Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available.