Effects of Low-Level Light Therapy on Resting-State Connectivity Following Moderate Traumatic Brain Injury: Secondary Analyses of a Double-blinded Placebo-controlled Study.

Background Low-level light therapy (LLLT) has been shown to modulate recovery in patients with traumatic brain injury (TBI). However, the impact of LLLT on the functional connectivity of the brain when at rest has not been well studied. Purpose To use functional MRI to assess the effect of LLLT on whole-brain resting-state functional connectivity (RSFC) in patients with moderate TBI at acute (within 1 week), subacute (2-3 weeks), and late-subacute (3 months) recovery phases. Materials and Methods This is a secondary analysis of a prospective single-site double-blinded sham-controlled study conducted in patients presenting to the emergency department with moderate TBI from November 2015 to July 2019. Participants were randomized for LLLT and sham treatment. The primary outcome of the study was to assess structural connectivity, and RSFC was collected as the secondary outcome. MRI was used to measure RSFC in 82 brain regions in participants during the three recovery phases. Healthy individuals who did not receive treatment were imaged at a single time point to provide control values. The Pearson correlation coefficient was estimated to assess the connectivity strength for each brain region pair, and estimates of the differences in Fisher z-transformed correlation coefficients (hereafter, z differences) were compared between recovery phases and treatment groups using a linear mixed-effects regression model. These analyses were repeated for all brain region pairs. False discovery rate (FDR)-adjusted P values were computed to account for multiple comparisons. Quantile mixed-effects models were constructed to quantify the association between the Rivermead Postconcussion Symptoms Questionnaire (RPQ) score, recovery phase, and treatment group. Results RSFC was evaluated in 17 LLLT-treated participants (median age, 50 years [IQR, 25-67 years]; nine female), 21 sham-treated participants (median age, 50 years [IQR, 43-59 years]; 11 female), and 23 healthy control participants (median age, 42 years [IQR, 32-54 years]; 13 male). Seven brain region pairs exhibited a greater change in connectivity in LLLT-treated participants than in sham-treated participants between the acute and subacute phases (range of z differences, 0.37 [95% CI: 0.20, 0.53] to 0.45 [95% CI: 0.24, 0.67]; FDR-adjusted P value range, .010-.047). Thirteen different brain region pairs showed an increase in connectivity in sham-treated participants between the subacute and late-subacute phases (range of z differences, 0.17 [95% CI: 0.09, 0.25] to 0.26 [95% CI: 0.14, 0.39]; FDR-adjusted P value range, .020-.047). There was no evidence of a difference in clinical outcomes between LLLT-treated and sham-treated participants (range of differences in medians, -3.54 [95% CI: -12.65, 5.57] to -0.59 [95% CI: -7.31, 8.49]; P value range, .44-.99), as measured according to RPQ scores. Conclusion Despite the small sample size, the change in RSFC from the acute to subacute phases of recovery was greater in LLLT-treated than sham-treated participants, suggesting that acute-phase LLLT may have an impact on resting-state neuronal circuits in the early recovery phase of moderate TBI. ClinicalTrials.gov Identifier: NCT02233413 © RSNA, 2024 Supplemental material is available for this article.

Skin Cancer Awareness and Knowledge About Sun Protection Practices in Solid Organ Transplant Recipients: Patient Survey Study.

BACKGROUND: Adequate sun protection practices in chronically immunosuppressed patients can minimize the burden of the most common type of skin cancer in this population. In addition, early recognition of skin cancer by patients can lead to decreased morbidity, and possibly mortality from the disease. Nevertheless, there are significant gaps in the knowledge of sun protection measures and early recognition of skin cancer. OBJECTIVE: The aim of this study is to determine the risk factors of solid organ transplant recipients (SOTRs) for developing skin cancer and their sun exposure education and behavior post-transplantation. MATERIALS AND METHODS: This study evaluates the responses of 107 SOTRs on their outlooks and beliefs of sunscreen usage, skin cancer, and sun exposure knowledge. RESULTS: Our study identified several significant risk factors for the development of actinic keratosis or keratinocyte carcinoma in SOTRs including history of sunburn before age 18, blue eyes, history of tanning bed use, performing monthly skin exams, ability to identify precancerous skin lesions, and history of previous skin examinations. CONCLUSION: A patient-centered approach needs to be used to properly educate patients on effective ways to reduce excessive sun exposure. Regular skin examinations, and patients continued education are necessary components in reducing the burden of skin cancer in SOTRs.

Telomerase activity, telomere length, and the euploidy rate of human embryos.

BACKGROUND: Telomeres maintain chromosome stability, while telomerase counteracts their progressive shortening. Telomere length varies between cell types, with leukocyte telomere length (LTL) decreasing with age. Reduced telomerase activity has been linked to reproductive issues in females, such as low pregnancy rates and premature ovarian failure, with recent studies indicating correlations between telomere length in granulosa cells and IVF outcomes. OBJECTIVES: The study aims to explore the relationship between telomere length, telomerase activity, and euploid blastocyst rate in infertile women undergoing IVF/ICSI PGT-A cycles. METHODS: This prospective study involves 108 patients undergoing controlled ovarian stimulation and PGT-A. Telomere length and telomerase activity were measured in peripheral mononuclear cells and granulosa cells (GC), respectively. RESULTS: The telomere repeat copy number to single gene copy number ratio (T/S) results respectively 0.6 ± 0.8 in leukocytes and 0.7 ± 0.9 in GC. An inverse relationship was found between LTL and the patient's age (p < .01). A higher aneuploid rate was noticed in patients with short LTL, with no differences in ovarian reserve markers (p = .15), number of oocytes retrieved (p = .33), and number of MII (p = 0.42). No significant association was noticed between telomere length in GC and patients' age (p = 0.95), in ovarian reserve markers (p = 0.32), number of oocytes retrieved (p = .58), number of MII (p = .74) and aneuploidy rate (p = .65). CONCLUSION: LTL shows a significant inverse correlation with patient age and higher aneuploidy rates. Telomere length in GCs does not correlate with patient age or reproductive outcomes, indicating differential telomere dynamics between leukocytes and granulosa cells.

Glycemic Control in Patients Living With HIV Initiated on Integrase Inhibitor-Based Three-Drug Antiretroviral Therapy.

Background: The increased risk of cardio-metabolic disorders associated with people living with human immunodeficiency virus (HIV) is of growing importance. Given the broad adoption of integrase strand-transfer inhibitor (INSTI)-based antiretroviral therapy (ART) as first-line therapy for HIV, additional data are needed regarding the metabolic effects of these regimens. Objective: The purpose of this study is to assess glycemic control in patients started on INSTI-based 3-drug regimens over a 2-year period. Methods: A retrospective study was conducted on patients seen in the Brooklyn Hospital Center. Men and nonpregnant, nonlactating women aged 18 years or older with a diagnosis of HIV who were initiated on or switched to an ART consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an INSTI were included in the analysis. The primary endpoint is change in A1C from baseline (pre-INSTI initiation) to 2 years after initiation. Results: Two hundred fifty-one patients were eligible based on specified inclusion and exclusion criteria. Overall, a statistically significant increase in A1C was seen in all patients started on INSTI-based regimen (95% CI, 0.10-0.36; P < 0.001). Primarily patients on both elvitegravir-based and bictegravir-based regimens saw the most significant increase in A1C: 0.16% (95% CI, 0.04-0.27; P = 0.006) and 0.39% (95% CI, 0.02-0.76; P = 0.038), respectively. Conclusion and Relevance: Integrase strand-transfer inhibitor-based 3-drug ART was associated with a small but statistically significant increase in A1C over a 2-year period, requiring additional monitoring by clinicians.

New insights into the role of LH in early ovarian follicular growth: a possible tool to optimize follicular recruitment.

Evidence shows that LH participates in enhancing transition from the early stage to the antral stage of folliculogenesis. It has been demonstrated that functional LH receptors are expressed, albeit at a very low level and even in smaller follicles, during the phase that was traditionally considered to be gonadotrophin independent, suggesting a role for LH in accelerating the rate of progression of non-growing and primary follicles to the preantral/antral stage. Hypogonadotropic hypogonadism, together with other clinical conditions of pituitary suppression, has been associated with reduced functional ovarian reserve. The reduction in LH serum concentration is associated with a low concentration of anti-Müllerian hormone. This is the case in hypothalamic amenorrhoea, pregnancy, long-term GnRH-analogue therapy and hormonal contraception. The effect seems to be reversible, such that after pregnancy and after discontinuation of drugs, the functional ovarian reserve returns to the baseline level. Evidence suggests that women with similar primordial follicle reserves could present with different numbers of antral follicles, and that gonadotrophins may play a fundamental role in permitting a normal rate of progression of follicles through non-cyclic folliculogenesis. The precise role of gonadotrophins in early folliculogenesis, as well as their use to modify the functional ovarian reserve, must be investigated.

Risk of melanoma and nonmelanoma skin cancer with immunosuppressants, part II: Methotrexate, alkylating agents, biologics, and small molecule inhibitors.

In solid organ transplant recipients, skin cancer risk associated with posttransplant immunosuppression has been well-described, and screening practices generally reflect these risks. In addition to agents used posttransplant, other classes of immunosuppressants also have the potential to raise the risk of nonmelanoma skin cancer (NMSC) or melanoma. In the present manuscript, the evidence for melanoma and NMSC risk associated with methotrexate, cyclophosphamide, biologic cytokine inhibitors including TNF (tumor necrosis factor)-alpha and interleukin inhibitors, costimulation blockers such as abatacept, integrin inhibitors such as natalizumab, targeted B-cell, and T-cell inhibitors including CD20 (cluster of differentiate 20), CD52, and BTK (Bruton's tyrosine kinase) inhibitors, and JAK (Janus kinase) inhibitors is reviewed. Based on the available data, we recommend regular skin cancer screening for select nontransplant patients receiving immunosuppressive regimens that are shown to raise the risk of NMSC or melanoma. We also offer suggestions for conscientious use of these therapies in high-risk patients. Finally, a comprehensive summary of the relative risk associated with each immunosuppressant class and associated recommendations is presented.

Risk of melanoma and nonmelanoma skin cancer with immunosuppressants, part I: Calcineurin inhibitors, thiopurines, IMDH inhibitors, mTOR inhibitors, and corticosteroids.

Immunosuppression is a well-documented risk factor for skin cancer, as exemplified by the 65- to 250-fold higher squamous cell carcinoma risk, 10-fold higher basal cell carcinoma risk, and 0 to 8-fold higher melanoma risk in solid organ transplant recipients (SOTRs) receiving potent, prolonged courses of immunosuppressive therapies. Numerous immune system components have been shown to either suppress or promote tumor growth, and immunosuppressive drugs may have additional effects on proliferative pathways independent of the immune system. Thus, evaluation of the specific regimen by the dermatologist is key for assessing skin cancer risk in each patient. In the present manuscript, the immune-mediated mechanisms of skin cancer development and regression are first reviewed. Next, a synthesis of the evidence shows the differing effects of immunosuppressive agents commonly used in SOTRs on melanoma and nonmelanoma skin cancer risk. These include systemic calcineurin inhibitors, thiopurines, IMDH (inosine monophosphate dehydrogenase) inhibitors, mTOR (mammalian target of rapamycin) inhibitors, and systemic corticosteroids. Finally, recommendations for skin cancer screening in SOTRs are discussed. We further offer recommendations for select nontransplant patients who may benefit from routine skin cancer screening due to risks associated with specific immunosuppressant exposure, and we propose evidence-based strategies for minimizing high-risk immunosuppressant use in clinical practice.

Evidence for the expression of vasorin in the human female reproductive tissues.

Objective: To investigate the expression and localization of Vasorin (Vasn) in human female reproductive system. Methods: The presence of Vasorin was evaluated by RT-PCR and immunoblotting analyses in patient-derived endometrial, myometrial and granulosa cells (GCs) primary cultures. Immunostaining analyses were performed to detect Vasn localization in primary cultures and in ovarian and uterine tissues. Results: Vasn mRNA was detected in patient-derived endometrial, myometrial and GCs primary cultures without significant differences at the transcript level. Otherwise, immunoblotting analysis showed that Vasn protein levels were significantly higher in GCs than proliferative endometrial stromal cells (ESCs) and myometrial cells. Immunohistochemistry performed in ovarian tissues revealed that Vasn was expressed in the GCs of ovarian follicles at different stages of development with a higher immunostaining signal in mature ovarian follicles such as the antral follicle or on the surface of cumulus oophorus cells than in early-stage follicles. The immunostaining of uterine tissues showed that Vasn was expressed in the proliferative stroma endometrium while it was significantly less expressed in the secretory endometrium. Conversely, no protein immunoreactivity was revealed in health myometrial tissue. Conclusions: Our results revealed the presence of Vasn in the ovary and the endometrium. The pattern of Vasn expression and distribution suggests that this protein may have a role in the regulation of processes such as folliculogenesis, oocyte maturation, and endometrial proliferation.

An artificial intelligence-accelerated 2-minute multi-shot echo planar imaging protocol for comprehensive high-quality clinical brain imaging.

PURPOSE: We introduce and validate an artificial intelligence (AI)-accelerated multi-shot echo-planar imaging (msEPI)-based method that provides T1w, T2w, T2∗ , T2-FLAIR, and DWI images with high SNR, high tissue contrast, low specific absorption rates (SAR), and minimal distortion in 2 minutes. METHODS: The rapid imaging technique combines a novel machine learning (ML) scheme to limit g-factor noise amplification and improve SNR, a magnetization transfer preparation module to provide clinically desirable contrast, and high per-shot EPI undersampling factors to reduce distortion. The ML training and image reconstruction incorporates a tunable parameter for controlling the level of denoising/smoothness. The performance of the reconstruction method is evaluated across various acceleration factors, contrasts, and SNR conditions. The 2-minute protocol is directly compared to a 10-minute clinical reference protocol through deployment in a clinical setting, where five representative cases with pathology are examined. RESULTS: Optimization of custom msEPI sequences and protocols was performed to balance acquisition efficiency and image quality compared to the five-fold longer clinical reference. Training data from 16 healthy subjects across multiple contrasts and orientations were used to produce ML networks at various acceleration levels. The flexibility of the ML reconstruction was demonstrated across SNR levels, and an optimized regularization was determined through radiological review. Network generalization toward novel pathology, unobserved during training, was illustrated in five clinical case studies with clinical reference images provided for comparison. CONCLUSION: The rapid 2-minute msEPI-based protocol with tunable ML reconstruction allows for advantageous trade-offs between acquisition speed, SNR, and tissue contrast when compared to the five-fold slower standard clinical reference exam.

Extended LH administration as a strategy to increase the pool of recruitable antral follicles in hypothalamic amenorrhea: evidence from a case series.

New evidence is indicating a growing role of LH in promoting ovarian follicular growth and maturation, even at the early stages. LH seems to enhance the transition of follicles to the antral stage hence leading to an increase in the so-called functional ovarian reserve (recruitable antral follicles). Hypogonadotropic hypogonadism is characterized by low, and sometimes undetectable, serum LH and FSH levels, which may indeed explain the low anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) found in patients affected by this condition. We report here the cases of two young women affected by hypothalamic amenorrhea (HA) that presented for fertility treatment with very low functional ovarian reserve. The two patients were treated with exogenous LH for 1 and 2 months (extended LH administration: ELHA) at the dose of 187.5 IU LH every day and 150 IU LH every other day, respectively. In both the cases there was an increase in serum AMH levels and in the AFC. In one patient, the AMH and AFC increased from a baseline 1.3 ng/ml and 8 to 2.3 ng/ml and 14 at end of treatment, respectively. In the second case, serum AMH and AFC increased from 0.4 ng/ml and 6 to 1.6 ng/ml and 13, respectively. One patient underwent ovarian stimulation before and after ELHA, showing an increase in the number of mature oocytes recruited (3 versus 8 metaphase II (MII) oocytes before and after, respectively). The second patient underwent an IVF cycle after ELHA resulting in the retrieval of six MII oocytes and an ongoing pregnancy following transfer of a single blastocyst. Women with HA are characterized by chronic, low levels of gonadotrophins, which may impact not only on the cyclic recruitment of follicles but also the progression of small growing follicles through the first stages of folliculogenesis. Some women with HA may in fact show very low serum AMH and AFC. Our case series shows that the administration of LH at a dose of at least 150-187.5 IU every day or every other day may contribute to a clinically evident increase in the functional ovarian reserve (AFC), and probably accounts for a positive effect of LH on the progression of follicles throughout the early stages of folliculogenesis.

The number and rate of euploid blastocysts in women undergoing IVF/ICSI cycles are strongly dependent on ovarian reserve and female age.

STUDY QUESTION: Can the possibility of having at least one euploid blastocyst for embryo transfer and the total number of euploid blastocysts be predicted for couples before they enter the IVF programme? SUMMARY ANSWER: Ovarian reserve and female age are the most important predictors of having at least one euploid blastocyst and the total number of euploid blastocysts. WHAT IS KNOWN ALREADY: The blastocyst euploidy rate among women undergoing ART has already been shown to significantly decrease with increasing female age, and the total number of euploid embryos is dependent on the blastocyst cohort size. However, the vast majority of published studies are based on retrospective analysis of data. STUDY DESIGN, SIZE, DURATION: This prospective analysis included 847 consecutively enrolled couples approaching their first preimplantation genetic testing for aneuploidies (PGT-A) cycle between 2017 and 2020. Only couples for whom ejaculated sperm was available and women with a BMI of <35 kg/m2 were included in the study. Only the first cycle was included for each patient. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at an IVF centre where, for all patients, the planned treatment was to obtain embryos at the blastocyst stage for the PGT-A programme. The impact of the following covariates was investigated: a woman's serum AMH level, age, height, weight and BMI and a man's age, height, weight, BMI, sperm volume and sperm motility and morphology. The analysis was performed with a machine learning (ML) approach. Models were fit on the training set (677 patients) and their predictive performance was then evaluated on the test set (170 patients). MAIN RESULTS AND ROLE OF CHANCE: After ovarian stimulation and oocyte insemination, 40.1% of couples had at least one blastocyst available for the PGT-A. Of 1068 blastocysts analysed, 33.6% were euploid. Two distinct ML models were fit: one for the probability of having at least one euploid blastocyst and one for the number of euploid blastocysts obtained. In the training set of patients, the variable importance plots of both models indicated that AMH and the woman's age are by far the most important predictors. Specifically, a positive association between the outcome and AMH and a negative association between the outcome and female age appeared. Gradient-boosted modelling offers a greater predictive performance than generalized additive models (GAMs). LIMITATIONS, REASONS FOR CAUTION: The study was performed based on data from a single centre. While this provides a robust set of data with a constant ART process and laboratory practice, the model might be suitable only for the evaluated population, which may limit the generalization of the model to other populations. WIDER IMPLICATIONS OF THE FINDINGS: ML models indicate that for couples entering the IVF/PGT-A programme, ovarian reserve, which is known to vary with age, is the most important predictor of having at least one euploid embryo. According to the GAM, the probability of a 30-year-old woman having at least one euploid embryo is 28% or 47% if her AMH level is 1 or 3 ng/ml, respectively; if the woman is 40 years old, this probability is 18% with an AMH of 1 ng/ml and 30% with an AMH of 3 ng/ml. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by an unrestricted grant from Gedeon Richter. The authors declared no conflict of interests. TRIAL REGISTRATION NUMBER: N/A.

Clinical validation of Wave-CAIPI susceptibility-weighted imaging for routine brain MRI at 1.5 T.

OBJECTIVES: Wave-CAIPI (Controlled Aliasing in Parallel Imaging) enables dramatic reduction in acquisition time of 3D MRI sequences such as 3D susceptibility-weighted imaging (SWI) but has not been clinically evaluated at 1.5 T. We sought to compare highly accelerated Wave-CAIPI SWI (Wave-SWI) with two alternative standard sequences, conventional three-dimensional SWI and two-dimensional T2*-weighted Gradient-Echo (T2*w-GRE), in patients undergoing routine brain MRI at 1.5 T. METHODS: In this study, 172 patients undergoing 1.5 T brain MRI were scanned with a more commonly used susceptibility sequence (standard SWI or T2*w-GRE) and a highly accelerated Wave-SWI sequence. Two radiologists blinded to the acquisition technique scored each sequence for visualization of pathology, motion and signal dropout artifacts, image noise, visualization of normal anatomy (vessels and basal ganglia mineralization), and overall diagnostic quality. Superiority testing was performed to compare Wave-SWI to T2*w-GRE, and non-inferiority testing with 15% margin was performed to compare Wave-SWI to standard SWI. RESULTS: Wave-SWI performed superior in terms of visualization of pathology, signal dropout artifacts, visualization of normal anatomy, and overall image quality when compared to T2*w-GRE (all p < 0.001). Wave-SWI was non-inferior to standard SWI for visualization of normal anatomy and pathology, signal dropout artifacts, and overall image quality (all p < 0.001). Wave-SWI was superior to standard SWI for motion artifact (p < 0.001), while both conventional susceptibility sequences were superior to Wave-SWI for image noise (p < 0.001). CONCLUSIONS: Wave-SWI can be performed in a 1.5 T clinical setting with robust performance and preservation of diagnostic quality. KEY POINTS: • Wave-SWI accelerated the acquisition of 3D high-resolution susceptibility images in 70% of the acquisition time of the conventional T2*GRE. • Wave-SWI performed superior to T2*w-GRE for visualization of pathology, signal dropout artifacts, and overall diagnostic image quality. • Wave-SWI was noninferior to standard SWI for visualization of normal anatomy and pathology, signal dropout artifacts, and overall diagnostic image quality.

"All-in-one" window/level whole-body computed tomography scan - A faster way to evaluate trauma cases.

PURPOSE: To investigate the accuracy and total assessment time (TAT) of the "All-in-one" (AIO)-window/level setting for whole-body computed tomography (CT) image compared to multiple tissue-specific window/level settings conventionally used for detection of traumatic injuries. METHOD: Contrast-enhanced chest, abdomen, and pelvic CT scans of 50 patients who presented to our emergency department (ED) for major trauma were retrospectively selected. In a simulation of a "wet read" performed at the CT scanner console, 6 readers with different levels of experience had up to 3 min to describe any traumatic finding identified on the CTs. The readers reviewed each patient in two different sessions separated by a washout period to suppress any recall bias from one session to the next. Each scan was reviewed once using the AIO-window/level setting and another time using the conventional bone, lung, and soft tissue window/level display settings, in a randomized order. The CT reports were used as reference standard. RESULTS: Overall, there was no statistically significant difference in the assessment accuracy of the review based on the AIO or the conventional window/level settings (0.89 ± 0.09 vs 0.90 ± 0.08). Using the AIO-window/level settings, TAT was 14.3 s faster when compared with the conventional window/level settings (2.33 ± 0.63 vs 2.57 ± 0.51 min; p < 0.001). CONCLUSIONS: In a time-delimited image review, similar diagnostic accuracy was reached faster using the AIO vs the conventional window/level settings. When providing a "wet read" at the CT console, the ability to identify traumatic injury using a single AIO-window/level may help expedite patient management.

Evaluation of highly accelerated wave controlled aliasing in parallel imaging (Wave-CAIPI) susceptibility-weighted imaging in the non-sedated pediatric setting: a pilot study.

BACKGROUND: Susceptibility-weighted imaging (SWI) is highly sensitive for intracranial hemorrhagic and mineralized lesions but is associated with long scan times. Wave controlled aliasing in parallel imaging (Wave-CAIPI) enables greater acceleration factors and might facilitate broader application of SWI, especially in motion-prone populations. OBJECTIVE: To compare highly accelerated Wave-CAIPI SWI to standard SWI in the non-sedated pediatric outpatient setting, with respect to the following variables: estimated scan time, image noise, artifacts, visualization of normal anatomy and visualization of pathology. MATERIALS AND METHODS: Twenty-eight children (11 girls, 17 boys; mean age ± standard deviation [SD] = 128.3±62 months) underwent 3-tesla (T) brain MRI, including standard three-dimensional (3-D) SWI sequence followed by a highly accelerated Wave-CAIPI SWI sequence for each subject. We rated all studies using a predefined 5-point scale and used the Wilcoxon signed rank test to assess the difference for each variable between sequences. RESULTS: Wave-CAIPI SWI provided a 78% and 67% reduction in estimated scan time using the 32- and 20-channel coils, respectively, corresponding to estimated scan time reductions of 3.5 min and 3 min, respectively. All 28 children were imaged without anesthesia. Inter-reader agreement ranged from fair to substantial (k=0.67 for evaluation of pathology, 0.55 for anatomical contrast, 0.3 for central noise, and 0.71 for artifacts). Image noise was rated higher in the central brain with wave SWI (P<0.01), but not in the peripheral brain. There was no significant difference in the visualization of normal anatomical structures and visualization of pathology between the standard and wave SWI sequences (P=0.77 and P=0.79, respectively). CONCLUSION: Highly accelerated Wave-CAIPI SWI of the brain can provide similar image quality to standard SWI, with estimated scan time reduction of 3-3.5 min depending on the radiofrequency coil used, with fewer motion artifacts, at a cost of mild but perceptibly increased noise in the central brain.

Comparison of ultrafast wave-controlled aliasing in parallel imaging (CAIPI) magnetization-prepared rapid acquisition gradient echo (MP-RAGE) and standard MP-RAGE in non-sedated children: initial clinical experience.

BACKGROUND: Fast magnetic resonance imaging (MRI) sequences are advantageous in pediatric imaging as they can lessen child discomfort, decrease motion artifact and improve scanner availability. OBJECTIVE: To evaluate the feasibility of an ultrafast wave-CAIPI (controlled aliasing in parallel imaging) MP-RAGE (magnetization-prepared rapid gradient echo) sequence for brain imaging of awake pediatric patients. MATERIALS AND METHODS: Each MRI included a standard MP-RAGE sequence and an ultrafast wave-MP-RAGE sequence. Two neuroradiologists evaluated both sequences in terms of artifacts, noise, anatomical contrast and pathological contrast. A predefined 5-point scale was used by two independent pediatric neuroradiologists. A Wilcoxon signed-rank test was used to evaluate the difference between sequences for each variable. RESULTS: Twenty-four patients (14 males; mean age: 11.5±4.5 years, range: 1 month to 17.8 years) were included. Wave-CAIPI MP-RAGE provided a 77% reduction in scan time using a 32-channel coil and a 70% reduction using a 20-channel coil. Visualization of the pathology, artifacts and pathological enhancement (including parenchymal, leptomeningeal and dural enhancement) was not significantly different between standard MP-RAGE and wave-CAIPI MP-RAGE (all P>0.05). For central (P<0.001) and peripheral (P<0.001) noise, and the evaluation of the anatomical structures (P<0.001), the observers favored standard MP-RAGE over wave-CAIPI MP-RAGE. CONCLUSION: Ultrafast brain imaging with wave-CAIPI MP-RAGE is feasible in awake pediatric patients, providing a substantial reduction in scan time at a cost of subjectively increased image noise.

Reactive angioendotheliomatosis associated with antiphospholipid syndrome.

Reactive angioendotheliomatosis (RAE) is an uncommon, benign, antiproliferative condition associated with systemic diseases that may cause occlusion or inflammation of the vascular lumina. A link between antiphospholipid syndrome (APS) and RAE has been reported a few times in the literature. Herein, we present a unique case of RAE diagnosed in a patient with primary APS who was well-managed on warfarin and rituximab with no recent thrombotic events. As RAE can precede or follow a diagnosis of APS, the presence of the condition indicates a need to workup for APS and to ensure those with the condition are adequately anticoagulated. However, as demonstrated in this case, the condition can still occur in patients who are adequately anticoagulated.

Determinants of cerebral radiological progression in Fabry disease.

BACKGROUND AND AIM: It is unclear which patients with Fabry disease (FD) are at risk for progression of white matter lesions (WMLs) and brain infarctions and whether enzyme replacement therapy (ERT) changes this risk. The aim of this study was to determine the effect of ERT and clinical characteristics on progression of WMLs and infarctions on MRI in patients with FD. METHODS: MRIs were assessed for WMLs (Fazekas scale), infarctions and basilar artery diameter (BAD). The effect of clinical characteristics (renal and cardiac involvement, cardiovascular risk factors, cardiac complications, BAD) and ERT on WML and infarction progression was evaluated using mixed models. RESULTS: One hundred forty-nine patients were included (median age: 39 years, 38% men, 79% classical phenotype). Median follow-up time was 7 years (range: 0-13 years) with a median number of MRIs per patient of 5 (range: 1-14), resulting in a total of 852 scans. Variables independently associated with WML and infarction progression were age, male sex and a classical phenotype. Progression of WMLs and infarctions was not affected by adding ERT to the model, neither for the whole group, nor for early treated patients. Progression was highly variable among patients which could not be explained by other known variables such as hypertension, cholesterol, atrial fibrillation and changes in kidney function, left ventricular mass or BAD. CONCLUSION: Progression of WMLs and cerebral infarctions in FD is mainly related to age, sex and phenotype. Additional effects of established cardiovascular risk factors, organ involvement and treatment with ERT are probably small to negligible.

Cognitive functioning and depressive symptoms in Fabry disease: A follow-up study.

Patients with Fabry disease (FD) have a high prevalence of depressive symptoms and can suffer from cognitive impairment, negatively affecting their life. The course of cognitive functioning and depressive symptoms in FD is unknown. The aim of this prospective cohort study was to describe changes in cognitive functioning and depressive symptoms and to identify related variables in patients with FD over 1 year. Assessments were conducted twice, using a neuropsychological test battery and the Centre of Epidemiological Studies Depression scale (CESD). Eighty-one patients were included of which 76 patients (94%) completed both assessments (age: 44 years, 34% men, 75% classical phenotype). A significant decrease in cognitive functioning was found in four patients (5%), with patients regressing from excellent to average/good. Changes were not related to sex, phenotype, stroke, IQ or CESD scores. CESD scores ≥16 were present in 29 patients (38%) at baseline. Using the reliable change index a decrease in CESD scores was found in six patients (8%). Decreased CESD scores were independently related to employing a positive and problem solving coping style and increased CESD scores to an avoiding and brooding coping style and worsening health perception. We found no major changes in cognitive functioning in patients with FD during 1 year follow-up making it an unsuitable outcome in FD treatment trials. Considering the high prevalence of persistent depressive symptoms, assessment of depressive symptoms should be part of routine follow-up. Altering coping styles and health perception may improve psychological well-being in FD.

Scar sarcoidosis following rituximab therapy.

Drug-induced sarcoidosis has been rarely described but it constitutes a potential side effect of immunomodulatory medications. We report a case of rituximab-induced scar sarcoidosis and review similar published cases. Although there is evidence of B-cell dysregulation in the pathogenesis of sarcoidosis, the use of rituximab for this disease needs to be carefully evaluated based on reports of worsening and de novo development of sarcoidosis after rituximab therapy.