Vessel wall MR imaging of central nervous system vasculitis: a systematic review.

PURPOSE: Beyond vessel wall enhancement, little is understood about vessel wall MR imaging (VW-MRI) features of vasculitis affecting the central nervous system (CNS). We reviewed vessel wall MR imaging patterns of inflammatory versus infectious vasculitis and also compared imaging patterns for intracranial versus extracranial arteries of the head and neck. METHODS: Studies reporting vasculitis of the CNS/head and neck and included MR imaging descriptions of vessel wall features were identified by searching PubMed, Scopus, Cochrane, Web of Science, and EMBASE up to June 10, 2020. From 6065 publications, 115 met the inclusion criteria. Data on study characteristics, vasculitis type, MR details, and VW-MRI descriptions were extracted. RESULTS: Studies used VW-MRI for inflammatory (64%), infectious (17%), or both inflammatory and infectious vasculitides (19%). Vasculitis affecting intracranial versus extracranial arteries were reported in 58% and 39% of studies, respectively. Commonly reported VW-MRI features were vessel wall enhancement (89%), thickening (72%), edema (10%), and perivascular enhancement (16%). Inflammatory vasculitides affecting the intracranial arteries were less frequently reported to have vessel wall thickening (p = 0.006) and perivascular enhancement (p = 0.001) than extracranial arteries. Varicella zoster/herpes simplex vasculitis (VZV/HSV, 45%) and primary angiitis of the CNS (PACNS, 22%) were the most commonly reported CNS infectious and inflammatory vasculitides, respectively. Patients with VZV/HSV vasculitis more frequently showed decreased or resolution of vessel wall enhancement after therapy compared to PACNS (89% versus 59%). CONCLUSIONS: To establish imaging biomarkers of vessel wall inflammation in the CNS, VW-MRI features of vasculitis accounting for disease mechanism and anatomy should be better understood.

Imaging endpoints of intracranial atherosclerosis using vessel wall MR imaging: a systematic review.

PURPOSE: The vessel wall MR imaging (VWI) literature was systematically reviewed to assess the criteria and measurement methods of VWI-related imaging endpoints for symptomatic intracranial plaque in patients with ischemic events. METHODS: PubMed, Scopus, Web of Science, EMBASE, and Cochrane databases were searched up to October 2019. Two independent reviewers extracted data from 47 studies. A modified Guideline for Reporting Reliability and Agreement Studies was used to assess completeness of reporting. RESULTS: The specific VWI-pulse sequence used to identify plaque was reported in 51% of studies. A VWI-based criterion to define plaque was reported in 38% of studies. A definition for culprit plaque was reported in 40% of studies. Frequently scored qualitative imaging endpoints were plaque quadrant (21%) and enhancement (21%). Frequently measured quantitative imaging endpoints were stenosis (19%), lumen area (15%), and remodeling index (14%). Reproducibility for all endpoints ranged from good to excellent (range: ICCT1 hyperintensity = 0.451 to ICCstenosis = 0.983). However, rater specialty and years of experience varied among studies. CONCLUSIONS: Investigators are using different criteria to identify and measure VWI-imaging endpoints for culprit intracranial plaque. Early awareness of these differences to address methods of acquisition and measurement will help focus research resources and efforts in technique optimization and measurement reproducibility. Consensual definitions to detect plaque will be important to develop automatic lesion detection tools particularly in the era of radiomics.

Age-dependent changes in electrophysiology and calcium handling: implications for pediatric cardiac research.

Rodent models are frequently employed in cardiovascular research, yet our understanding of pediatric cardiac physiology has largely been deduced from more simplified two-dimensional cell studies. Previous studies have shown that postnatal development includes an alteration in the expression of genes and proteins involved in cell coupling, ion channels, and intracellular calcium handling. Accordingly, we hypothesized that postnatal cell maturation is likely to lead to dynamic alterations in whole heart electrophysiology and calcium handling. To test this hypothesis, we employed multiparametric imaging and electrophysiological techniques to quantify developmental changes from neonate to adult. In vivo electrocardiograms were collected to assess changes in heart rate, variability, and atrioventricular conduction (Sprague-Dawley rats). Intact, whole hearts were transferred to a Langendorff-perfusion system for multiparametric imaging (voltage, calcium). Optical mapping was performed in conjunction with an electrophysiology study to assess cardiac dynamics throughout development. Postnatal age was associated with an increase in the heart rate (181 ± 34 vs. 429 ± 13 beats/min), faster atrioventricular conduction (94 ± 13 vs. 46 ± 3 ms), shortened action potentials (APD80: 113 ± 18 vs. 60 ± 17 ms), and decreased ventricular refractoriness (VERP: 157 ± 45 vs. 57 ± 14 ms; neonatal vs. adults, means ± SD, P < 0.05). Calcium handling matured with development, resulting in shortened calcium transient durations (168 ± 18 vs. 117 ± 14 ms) and decreased propensity for calcium transient alternans (160 ± 18- vs. 99 ± 11-ms cycle length threshold; neonatal vs. adults, mean ± SD, P < 0.05). Results of this study can serve as a comprehensive baseline for future studies focused on pediatric disease modeling and/or preclinical testing.NEW & NOTEWORTHY This is the first study to assess cardiac electrophysiology and calcium handling throughout postnatal development, using both in vivo and whole heart models.

Mindfulness-based group intervention in adolescents at-risk for excess weight gain: A randomized controlled pilot study.

OBJECTIVES: To assess feasibility/acceptability of a mindfulness-based approach to excess weight prevention in adolescents at-risk for excess weight gain. To pilot test efficacy of a mindfulness-based intervention for improving food reward sensitivity, stress-eating, executive function (EF), and BMI/adiposity. METHODS: A pilot randomized controlled trial was conducted with 12-17y adolescents at-risk for excess weight gain based on above-average weight (body mass index [BMI]≥70%ile) or parental history of obesity (BMI≥30 kg/m2). Adolescents were randomized to a mindfulness-based (n = 29) or health education control group (n = 25) that met for six weekly one-hour sessions. Feasibility/acceptability were determined from attendance and acceptability survey ratings. At baseline, six-week and six-month follow-up, adolescents' perceived stress was measured with the Perceived Stress Scale, food reward sensitivity with a behavioral task, stress-eating during a laboratory test meal, and EF with the parent-reported Behavior Rating Inventory of Executive Function and NIH Toolbox. At the same intervals, BMI indices and body fat by air displacement plethysmography were assessed in a fasted state. RESULTS: Median session attendance was 6:6 sessions in both conditions; program acceptability ratings were above-average. Compared to health education, adolescents in mindfulness had lower food reward sensitivity at six-months (Cohen's d = 0.64, p = .01). There were no between-condition differences in BMI (mindfulness vs. health educationΔsix-months 95%CI 0.20, 1.52 kg/m2 vs. 0.21, 1.62 kg/m2) or adiposity (-3.64, -0.61% vs. -4.31, -1.04%) changes. CONCLUSIONS: A mindfulness-based group intervention is feasible/acceptable among adolescents at-risk for excess weight. In this pilot sample, mindfulness and health education were equivocal for BMI/adiposity outcomes. Future trials with a larger, adequately-powered sample and longer-term follow-up are necessary to test efficacy of a mindfulness-based intervention for food reward sensitivity, stress-eating, EF, and stabilizing growth trajectories in youth at-risk for adult obesity.

Combined Orbital and Cranial Vessel Wall Magnetic Resonance Imaging for the Assessment of Disease Activity in Giant Cell Arteritis.

OBJECTIVE: Acute visual impairment is the most feared complication of giant cell arteritis (GCA) but is challenging to predict. Magnetic resonance imaging (MRI) evaluates orbital pathology not visualized by an ophthalmologic examination. This study combined orbital and cranial vessel wall MRI to assess both orbital and cranial disease activity in patients with GCA, including patients without visual symptoms. METHODS: Patients with suspected active GCA who underwent orbital and cranial vessel wall MRI were included. In 14 patients, repeat imaging over 12 months assessed sensitivity to change. Clinical diagnosis of ocular or nonocular GCA was determined by a rheumatologist and/or ophthalmologist. A radiologist masked to clinical data scored MRI enhancement of structures. RESULTS: Sixty-four patients with suspected GCA were included: 25 (39%) received a clinical diagnosis of GCA, including 12 (19%) with ocular GCA. Orbital MRI enhancement was observed in 83% of patients with ocular GCA, 38% of patients with nonocular GCA, and 5% of patients with non-GCA. MRI had strong diagnostic performance for both any GCA and ocular GCA. Combining MRI with a funduscopic examination reached 100% sensitivity for ocular GCA. MRI enhancement significantly decreased after treatment (P < 0.01). CONCLUSION: In GCA, MRI is a sensitive tool that comprehensively evaluates multiple cranial structures, including the orbits, which are the most concerning site of pathology. Orbital enhancement in patients without visual symptoms suggests that MRI may detect at-risk subclinical ocular disease in GCA. MRI scores decreased following treatment, suggesting scores reflect inflammation. Future studies are needed to determine if MRI can identify patients at low risk for blindness who may receive less glucocorticoid therapy.

Transfusion-Associated Hyperkalemic Cardiac Arrest in Neonatal, Infant, and Pediatric Patients.

Red blood cell (RBC) transfusions are a life-saving intervention, with nearly 14 million RBC units transfused in the United States each year. However, the safety and efficacy of this procedure can be influenced by variations in the collection, processing, and administration of RBCs. Procedures or manipulations that increase potassium (K+) levels in stored blood products can also predispose patients to hyperkalemia and transfusion-associated hyperkalemic cardiac arrest (TAHCA). In this mini review, we aimed to provide a brief overview of blood storage, the red cell storage lesion, and variables that increase extracellular [K+]. We also summarize cases of TAHCA and identify potential mitigation strategies. Hyperkalemia and cardiac arrhythmias can occur in pediatric patients when RBCs are transfused quickly, delivered directly to the heart without time for electrolyte equilibration, or accumulate extracellular K+ due to storage time or irradiation. Advances in blood banking have improved the availability and quality of RBCs, yet, some patient populations are sensitive to transfusion-associated hyperkalemia. Future research studies should further investigate potential mitigation strategies to reduce the risk of TAHCA, which may include using fresh RBCs, reducing storage time after irradiation, transfusing at slower rates, implementing manipulations that wash or remove excess extracellular K+, and implementing restrictive transfusion strategies.

Application of Point-of-Care Ultrasound for Family Medicine Physicians for Abdominopelvic and Soft Tissue Assessment.

Point-of-care ultrasound (POCUS) improves both the sensitivity and specificity with which clinicians can make a variety of diagnoses at the bedside from abdominal aortic aneurysm to kidney stones. In outpatient clinics, urgent care centers, and emergency departments, where ultrasound imaging may be delayed by hours or even days, the use of POCUS can be very helpful. We believe that POCUS facilitates both the triage of patients and provides diagnostic information quickly. We hope to advance the use of POCUS in the primary care setting and have reviewed six sonographic topics where we believe ultrasound can be of immense assistance to the physician in the outpatient setting.

MR Intracranial Vessel Wall Imaging: A Systematic Review.

The purpose of this systematic review is to identify trends and extent of variability in intracranial vessel wall MR imaging (VWI) techniques and protocols. Although variability in selection of protocol design and pulse sequence type is known, data on what and how protocols vary are unknown. Three databases were searched to identify publications using intracranial VWI. Publications were screened by predetermined inclusion/exclusion criteria. Technical development publications were scored for completeness of reporting using a modified Nature Reporting Summary Guideline to assess reproducibility. From 2,431 articles, 122 met the inclusion criteria. Trends over the last 23 years (1995-2018) show increased use of 3-Tesla MR (P < .001) and 3D volumetric T1-weighted acquisitions (P < .001). Most (65%) clinical VWI publications report achieving a noninterpolated in-plane spatial resolution of ≤.55 mm. In the last decade, an increasing number of technical development (n = 20) and 7 Tesla (n = 12) publications have been published, focused on pulse sequence development, improving cerebrospinal fluid suppression, scan efficiency, and imaging ex vivo specimen for histologic validation. Mean Reporting Summary Score for the technical development publications was high (.87, range: .63-1.0) indicating strong scientific technical reproducibility. Innovative work continues to emerge to address implementation challenges. Gradual adoption into the research and scientific community was suggested by a shift in the name in the literature from "high-resolution MR" to "vessel wall imaging," specifying diagnostic intent. Insight into current practices and identifying the extent of technical variability in the literature will help to direct future clinical and technical efforts to address needs for implementation.

Optocardiography and Electrophysiology Studies of Ex Vivo Langendorff-perfused Hearts.

Small animal models are most commonly used in cardiovascular research due to the availability of genetically modified species and lower cost compared to larger animals. Yet, larger mammals are better suited for translational research questions related to normal cardiac physiology, pathophysiology, and preclinical testing of therapeutic agents. To overcome the technical barriers associated with employing a larger animal model in cardiac research, we describe an approach to measure physiological parameters in an isolated, Langendorff-perfused piglet heart. This approach combines two powerful experimental tools to evaluate the state of the heart: electrophysiology (EP) study and simultaneous optical mapping of transmembrane voltage and intracellular calcium using parameter sensitive dyes (RH237, Rhod2-AM). The described methodologies are well suited for translational studies investigating the cardiac conduction system, alterations in action potential morphology, calcium handling, excitation-contraction coupling and the incidence of cardiac alternans or arrhythmias.

A case of severe encephalitis while on PD-1 immunotherapy for recurrent clear cell ovarian cancer.

Recurrent clear cell ovarian carcinoma is a difficult to treat condition and early trial data has suggested a possible role for immune checkpoint inhibitors. Nivolumab is an anti-PD-1 immunotherapy that has been used in this setting. While immune related toxicity of these agents has been well described, the occurrence of immune specific neurotoxicity is thought to be rare. We present a case of severe encephalitis while on PD-1 immunotherapy for a recurrent ovarian clear cell cancer and we believe this to be the first such reported case associated with the use of PD-1 inhibitor monotherapy. In this case, a 64-year-old woman with persistent clear cell ovarian cancer on Nivolumab presented with a severe fever of unknown origin and delirium; initial imaging and diagnostic work-up suggested a neurological etiology, but with no clear source. We concluded that this was a severe case of immune related encephalitis, thought to be brought about by the anti-PD-1 immunotherapy which responded well to systemic corticosteroids and plasmapheresis and the patient able to make a full recovery. We present a summary of the case and its management as well as a review of the literature on the previously reported neurotoxicity's of PD-1 inhibitors.

Short duration testosterone infusions maintain male sex behavior in Syrian hamsters.

In most mammalian species, reduced androgen availability is associated with marked reductions in male sexuality; conversely, androgen replacement in castrated males restores sex behavior within a few weeks. Testosterone (T) pulse duration, amplitude, frequency, and inter-pulse interval may be as important as total amount of hormone in determining target tissue responsiveness. We remain ignorant of the number and duration of daily T pulses necessary and sufficient to sustain male mating behavior. An in-dwelling infusion system was employed to vary T-pulse frequencies and durations. Daily 4 h infusions of aqueous T (100 microg/0.064 ml) and twice daily 4 h pulses of T (each 50 microg/0.064 ml) were sufficient to maintain ejaculatory behavior of sexually experienced castrated hamsters for 11 weeks post-castration; castrated hamsters infused with vehicle ceased to display the ejaculatory pattern 3 weeks after gonadectomy. Circulating T concentrations of hormone-infused hamsters declined markedly 7 h after the termination of each infusion. These results establish that male sex behavior can be sustained with infusions of relatively low T concentrations for 4 h/day and suggests that the basal concentrations of T sustained by the gonad during inter-pulse intervals may not be necessary for maintenance of sex behavior. 4 h T infusions were sufficient to maintain penile and seminal vesicles weights, but not ventral prostate weights or flank gland dimensions; the threshold for maintaining male sex behavior is lower than that for some androgen-dependent peripheral structures. Development of effective androgen replacement regimens that sustain sex behavior in castrated animals may be useful in the design of androgen replacement therapy for hypogonadal men.

Photoperiodic regulation of compensatory testicular hypertrophy in hamsters.

In mammals, removal of one testis results in compensatory testicular hypertrophy (CTH) of the remaining gonad. Although CTH is ubiquitous among juveniles of many species, laboratory rats, laboratory mice, and humans unilaterally castrated in adulthood fail to display CTH. We documented CTH in pre- and postpubertally hemi-castrated Syrian and Siberian hamsters and tested whether day length affects CTH in juvenile and adult Siberian hamsters. Robust CTH was evident in long-day hemi-castrates of both species and was preceded by increased serum FSH concentrations in juvenile Siberian hamsters. In sharp contrast, CTH was undetectable in short-day hemi-castrated Siberian hamsters for several months and only made its appearance with the development of neuroendocrine refractoriness to short day lengths; serum FSH concentrations of juveniles also did not increase above sham-castrate values until the onset of refractoriness. Long-day hemi-castrated Siberian hamsters with hypertrophied testes underwent complete gonadal regression after transfer to short days, albeit at a reduced rate for the first 3 weeks of treatment. Blood testosterone concentrations of adult hamsters did not differ between long-day hemicastrates and sham-castrates 9-12 weeks after surgery. We conclude that CTH is suppressed by short day lengths in Siberian hamsters at all ages and stages of reproductive development; in short day lengths, but not long day lengths, the remaining testis produces sufficient negative feedback inhibition to restrain FSH hypersecretion and prevent CTH.