Improvements in balance reaction impairments following reactive balance training in individuals with sub-acute stroke: A prospective cohort study with historical control

ABSTRACT

Background

Reactive balance training (RBT) has been previously found to reduce fall risk in individuals with sub-acute stroke; however, our understanding of the effects of RBT on specific balance impairments is lacking.     

Exploring the Impact of Individual UVB Radiation Levels on Serum 25-Hydroxyvitamin D in Women Living in High Versus Low Latitudes: A Cross-Sectional Analysis from the D-SOL Study

Vitamin D can be synthesized in the skin via sunlight exposure as well as ingested through diet. Vitamin D deficiency is currently a major global public health issue, with increasing prevalence in both low and high latitude locations. This cross-sectional analysis aimed to compare the intensity of individual Ultraviolet B radiation levels between women of the same ethnicity living in England and Brazil, respectively; and to investigate the association with circulating 25(OH)D concentrations. We analysed data from 135 Brazilian women (England, n = 56, 51° N; Brazil, n = 79, 16° S) recruited for the D-SOL study (Interaction between Vitamin D Supplementation and Sunlight Exposure in Women Living in Opposite Latitudes). Serum 25(OH)D concentrations were analysed by high performance liquid chromatography tandem mass spectrometry (HPLC-MS), individual UVB radiation via UVB dosimeter badges and dietary intake via 4-day diet diaries. Anthropometric, skin phototype, sociodemographic and lifestyle patterns were also assessed. Mean serum 25(OH)D concentration of England residents was significantly lower than Brazil residents. Daily individual UVB radiation level showed a strong significant positive correlation with serum 25(OH)D concentrations. The required UVB radiation to achieve 75 nmol/L was 2.2 SED and 38.8% of the total variance in 25(OH)D concentrations was explained uniquely by daily individual UVB radiation, after controlling for the influence of age and body mass index. Thus, these results highlight the strong positive association between serum 25(OH)D concentrations and individual UVB radiation and the influence of different individual characteristics and behaviours. Collectively, these factors contribute to meaningful, country-specific, public health strategies and policies for the efficient prevention and treatment of vitamin D inadequacy.     

Synaptopodin Is Dispensable for Normal Podocyte Homeostasis but Is Protective in the Context of Acute Podocyte Injury

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Patterns of Use of Induction Therapy for T2N0 Esophageal Cancer

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Novel Risk Factors for Progression of Diabetic and Nondiabetic CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

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Effects of Oxygen Supplementation on Injectable and Inhalant Anesthesia in C57BL/6 Mice

Oxygen supplementation is rarely considered when anesthetizing laboratory mice, despite reports that mice become profoundly hypoxic under anesthesia. Little is known about the effects of hypoxia on anesthetic performance. This article focuses on the effects of oxygen supplementation on physiologic parameters and depth of anesthesia in male and female C57BL/6 mice. Anesthesia was performed via common injectable anesthetic protocols and with isoflurane. Mice anesthetized with injectable anesthesia received one of 3 drug protocols. Low-dose ketamine/xylazine (100/8 mg/kg) was chosen to provide immobilization of mice, suitable for imaging procedures. Medium-dose ketamine/xylazine/acepromazine (100/10/1 mg/kg) was chosen as a dose that has been recommended for surgical procedures. High-dose ketamine/xylazine/acepromazine (150/12/3 mg/kg) was chosen after pilot studies to provide a long duration of a deep plane of anesthesia. We also tested the effects of oxygen supplementation on the minimum alveolar concentration (MAC) of isoflurane in mice. Mice breathed supplemental 100% oxygen, room air, or medical air with 21% oxygen. Anesthetized mice that did not receive supplemental oxygen all became hypoxic, while hypoxia was prevented in mice that received oxygen. Oxygen supplementation did not affect the MAC of isoflurane. At the high injectable dose, all mice not receiving oxygen supplementation died while all mice receiving oxygen supplementation survived. At low and medium doses, supplemental oxygen reduced the duration of the surgical plane of anesthesia (low dose with oxygen: 22 ± 14 min; low dose without supplementation: 29 ± 18 min; medium dose with oxygen: 43 ± 18 min; medium dose without supplementation: 61 ± 27 min). These results suggest that mice anesthetized with injectable and inhalant anesthesia without supplemental oxygen are routinely hypoxic. This hypoxia prolongs the duration of anesthesia with injectable drug protocols and affects survival at high doses of injectable anesthetics. Because of variable responses to injectable anesthetics in mice, oxygen supplementation is recommended for all anesthetized mice.

Anesthesia is frequently required for mice used in biomedical research, but anecdotal communications suggest that mice receive significantly less anesthetic monitoring and supportive care than do other research species. Monitoring of anesthetized mice is often minimal due to lack of specialized monitoring equipment, and the fact that many rodent surgeries are performed by a single person who acts as both surgeon and anesthetist. Supportive care during anesthesia is limited by a lack of supporting experimental evidence. The lack of monitoring and supportive care may increase the mortality rate in anesthetized mice.Previous studies have shown that mice anesthetized with both inhalant and injectable anesthetics without supplemental oxygen become profoundly hypoxic.^{1,6,8,9,19,26,39,41} While mice in these studies appear to recover normally from anesthesia, little is known about the effects of hypoxia on physiologic parameters, anesthetic depth, and perioperative mortality. Respiratory complications, including hypoxia and hypoventilation, are second only to cardiovascular complications as a cause of perioperative mortality in veterinary species, and in humans, hypoxemia accounts for over 50% of deaths under anesthesia.⁴ To mitigate the risk of hypoxia under anesthesia, oxygen supplementation is commonly provided to anesthetized humans and animals, but is rarely provided to mice in research settings.^6,19All anesthetics affect respiratory function; ketamine and isoflurane are particularly known to cause respiratory depression in mice and rats by impairing the normal physiologic responses to hypoxemia and hypercapnia.^{9,12,20,23,28} The peripheral chemoreceptors, primarily in the carotid body, normally sense dropping arterial partial pressure of oxygen (PaO₂) while central chemoreceptors located in the medulla sense changes in pH and rising partial pressure of carbon dioxide (PaCO₂).^22,23,29,40 Both sets of chemoreceptors compensate by initiating increases in respiratory rate and tidal volume.^{23,28,31,34,40} Injectable and inhalant anesthetic agents depress the function of these chemoreceptors, preventing the increases in respiration that compensate for hypoxia and hypoventilation.^22,29Pulse oximetry is commonly used to monitor peripheral oxygen saturation and detect the presence of hypoxia. Pulse oximeters use the difference in light absorption of oxygenated hemoglobin and deoxygenated hemoglobin in arterial blood to provide an estimate of arterial oxygen content, abbreviated as SpO₂.¹⁷ An SpO₂ of less than 90% to 95% generally corresponds to a PaO₂ of less than 60 to 80 mm Hg, which is considered hypoxic in most species of mammals.^7,17 Because of the small size of mice, species-specific pulse oximetry equipment is necessary to obtain this measurement. Therefore, measurement of SpO₂ in anesthetized mice is not routinely performed, meaning that hypoxia under anesthesia generally goes unrecognized, and is likely more common than is appreciated by our field.The purpose of this study was to confirm that mice become hypoxic after receiving a ketamine/xylazine based anesthetic admixture or isoflurane, which are commonly used anesthetics in mice and to investigate the effects of oxygen supplementation on anesthetic depth, physiologic values, and anesthetic requirements in these mice.^9,35 We hypothesized that mice not receiving supplemental oxygen would be hypoxic, as indicated by lower SpO₂ while anesthetized, and that supplemental oxygen would correct this hypoxia. We also hypothesized that oxygen supplementation would increase the doses of injectable and inhalant anesthesia necessary to maintain mice at a surgical plane of anesthesia.     

A Diagnostic Algorithm for Posterior Fossa Tumors in Children: A Validation Study

BACKGROUND AND PURPOSE:Primary posterior fossa tumors comprise a large group of neoplasias with variable aggressiveness and short and long-term outcomes. This study aimed to validate the clinical usefulness of a radiologic decision flow chart based on previously published neuroradiologic knowledge for the diagnosis of posterior fossa tumors in children.MATERIALS AND METHODS:A retrospective study was conducted (from January 2013 to October 2019) at 2 pediatric referral centers, Children''s Hospital of Philadelphia, United States, and Great Ormond Street Hospital, United Kingdom. Inclusion criteria were younger than 18 years of age and histologically and molecularly confirmed posterior fossa tumors. Subjects with no available preoperative MR imaging and tumors located primarily in the brain stem were excluded. Imaging characteristics of the tumors were evaluated following a predesigned, step-by-step flow chart. Agreement between readers was tested with the Cohen κ, and each diagnosis was analyzed for accuracy.RESULTS:A total of 148 cases were included, with a median age of 3.4 years (interquartile range, 2.1–6.1 years), and a male/female ratio of 1.24. The predesigned flow chart facilitated identification of pilocytic astrocytoma, ependymoma, and medulloblastoma sonic hedgehog tumors with high sensitivity and specificity. On the basis of the results, the flow chart was adjusted so that it would also be able to better discriminate atypical teratoid/rhabdoid tumors and medulloblastoma groups 3 or 4 (sensitivity = 75%–79%; specificity = 92%–99%). Moreover, our adjusted flow chart was useful in ruling out ependymoma, pilocytic astrocytomas, and medulloblastoma sonic hedgehog tumors.CONCLUSIONS:The modified flow chart offers a structured tool to aid in the adjunct diagnosis of pediatric posterior fossa tumors. Our results also establish a useful starting point for prospective clinical studies and for the development of automated algorithms, which may provide precise and adequate diagnostic tools for these tumors in clinical practice.

In the past 10 years, there has been an exponential increase in knowledge of the molecular characteristics of pediatric brain tumors, which was only partially incorporated in the 2016 World Health Organization Classification of Tumors of the Central Nervous System.¹ The main update in the 2016 Classification was the introduction of the molecular profile of a tumor as an important factor for predicting different biologic behaviors of entities which, on histology, look very similar or even indistinguishable.² A typical example is the 4 main groups of medulloblastoma: wingless (WNT), sonic hedgehog (SHH) with or without the p53 mutation, group 3, and group 4. Although they may appear similar on microscopy, these categories have distinct molecular profiles, epidemiology, prognosis, and embryologic origin.³Subsequent to the publication of the 2016 World Health Organization Classification, further studies have identified even more molecular subgroups of medulloblastoma with possible prognostic implications⁴ and also at least 3 new molecular subgroups of atypical teratoid/rhabdoid tumor (AT/RT)⁵ and several subgroups of ependymoma.⁶ MR imaging shows promise as a technique for differentiating histologic tumors and their molecular subgroups. This capability relies on not only various imaging characteristics but also the location and spatial extension of the tumor, evident on MR imaging, which can be traced to the embryologic origin of the neoplastic cells.^5,7-10One approach to the challenge of identifying imaging characteristics of different tumors in children is to use artificial intelligence. Yet despite this exciting innovation, correctly identifying the location of the mass and its possible use as an element for differential diagnosis still requires the expertise of an experienced radiologist. Previously, D''Arco et al¹¹ proposed a flow chart (Fig 1) for the differential diagnosis of posterior fossa tumors in children based on epidemiologic, imaging signal, and location characteristics of the neoplasm. The aims of the current study were the following: 1) to validate, in a retrospective, large cohort of posterior fossa tumors from 2 separate pediatric tertiary centers, the diagnostic accuracy of that flow chart, which visually represents the neuroadiologist''s mental process in making a diagnosis of posterior fossa tumors in children, 2) to describe particular types of posterior fossa lesions that are not correctly diagnosed by the initial flow chart, and 3) to provide an improved, clinically accessible flow chart based on the results.Open in a separate windowFIG 1.Predesigned radiologic flow chart created according to the literature before diagnostic accuracy analysis. The asterisk indicates brain stem tumors excluded from the analysis. Double asterisks indicate relative to gray matter. Modified with permission from D''Arco et al.¹¹     

Evaluation of DISORDER: Retrospective Image Motion Correction for Volumetric Brain MRI in a Pediatric Setting

BACKGROUND AND PURPOSE:Head motion causes image degradation in brain MR imaging examinations, negatively impacting image quality, especially in pediatric populations. Here, we used a retrospective motion correction technique in children and assessed image quality improvement for 3D MR imaging acquisitions.MATERIALS AND METHODS:We prospectively acquired brain MR imaging at 3T using 3D sequences, T1-weighted MPRAGE, T2-weighted TSE, and FLAIR in 32 unsedated children, including 7 with epilepsy (age range, 2–18 years). We implemented a novel motion correction technique through a modification of k-space data acquisition: Distributed and Incoherent Sample Orders for Reconstruction Deblurring by using Encoding Redundancy (DISORDER). For each participant and technique, we obtained 3 reconstructions as acquired (Aq), after DISORDER motion correction (Di), and Di with additional outlier rejection (DiOut). We analyzed 288 images quantitatively, measuring 2 objective no-reference image quality metrics: gradient entropy (GE) and MPRAGE white matter (WM) homogeneity. As a qualitative metric, we presented blinded and randomized images to 2 expert neuroradiologists who scored them for clinical readability.RESULTS:Both image quality metrics improved after motion correction for all modalities, and improvement correlated with the amount of intrascan motion. Neuroradiologists also considered the motion corrected images as of higher quality (Wilcoxon z = −3.164 for MPRAGE; z = −2.066 for TSE; z = −2.645 for FLAIR; all P < .05).CONCLUSIONS:Retrospective image motion correction with DISORDER increased image quality both from an objective and qualitative perspective. In 75% of sessions, at least 1 sequence was improved by this approach, indicating the benefit of this technique in unsedated children for both clinical and research environments.

Head motion is a common cause of image degradation in brain MR imaging. Motion artifacts negatively impact MR image quality and therefore radiologists’ capacity to read the images, ultimately affecting patient clinical care.¹ Motion artifacts are more common in noncompliant patients,² but even in compliant adults, intrascan movement is reported in at least 10% of cases.³ For children who require high-resolution MR images, obtaining optimal image quality can be challenging, owing to the requirement to stay still over long durations needed for acquisition.⁴ Sedation can be an option, but it carries higher risks, costs, and preparation and recovery time.⁵In conditions such as intractable focal epilepsy, identification of an epileptogenic lesion is clinically important to guide surgical treatment. However, these lesions can be visually subtle, particularly in children in whom subtle cortical dysplasias are more common.⁶ Dedicated epilepsy MR imaging protocols use high-resolution 3D sequences to allow better cortical definition and free reformatting of orientation but involve acquisition times in the order of minutes, so data collection becomes more sensitive to motion.⁷For children in particular, multiple strategies are available for minimizing motion during MR examinations. Collaboration with play specialists using mock scanners and training or projecting a cartoon are good approaches to reduce anxiety.^8,9 These tools are not always available in clinical radiology and, even with these strategies, motion can still be an issue.¹⁰ Different scanning approaches to correct for intrascan motion have been proposed. Broadly, prospective methods track head motion in real time and modify the acquisition directions accordingly.¹¹ These approaches are applicable to a wide range of sequences but require optical systems with external tracking markers, sometimes uncomfortable or impractical, and extra setup can ultimately result in longer examinations. Furthermore, these approaches may also not be robust to continuous motion.^11-13 Retrospective techniques have also been proposed, in some cases relying on imaging navigators that are not compatible with all standard sequences or contrasts.¹²Here, we use a more general retrospective motion correction technique: Distributed and Incoherent Sample Orders for Reconstruction Deblurring by using Encoding Redundancy (DISORDER). In this method, k-space samples are reordered to enable retrospective motion correction during image reconstruction.¹⁴ Our hypothesis is that DISORDER improves clinical MR imaging quality and readability. To assess its use for clinical sequences, we acquired a dedicated epilepsy MR imaging protocol in 32 children across a wide age range. We used both objective image quality metrics and expert neuroradiologist ratings to evaluate the outcome after motion correction.     

Impact on Health-Related Quality of Life of Induction Chemotherapy Compared With Concurrent Cisplatin and Radiation Therapy in Patients With Head and Neck Cancer

AimsOrgan preservation, an important goal in the treatment of head and neck squamous cell carcinoma (HNSCC), may include induction chemotherapy and cisplatin with radiation therapy (CRT). To our knowledge, no reports have directly compared the impact of induction chemotherapy with that of CRT on health-related quality of life (HRQOL).Materials and methodsIn a phase II trial, we assessed the HRQOL of patients treated with induction chemotherapy followed by CRT. Eligible patients had stage III–IV HNSCC. HRQOL questionnaires were administered at baseline, the end of induction (EOI), the end of CRT (EOCRT) and after CRT. Functional Assessment of Cancer Therapy (FACT version 4) assessed HRQOL. We carried out a comparison of changes in HRQOL from baseline to EOI and from EOI to EOCRT. This trial is registered with ClinicalTrials.gov (NCT01566435).ResultsThirty patients were enrolled in the study. Most HRQOL questionnaires were completed (88%). The mean total FACT scores did not differ from baseline to EOI (general: 83.8 versus 79.1, P = 0.08; head and neck: 109.7 versus 105.8, P = 0.33; Total Outcome Index: 69.7 versus 62.3, P = 0.03; respectively, using P ≤ 0.01 to adjust for multiple simultaneous tests of differences). However, total FACT scores significantly worsened from EOI to EOCRT (79.1 versus 62.3, P = 0.01; 105.8 versus 74.2, P < 0.01; 62.3 versus 34.2, P = 0.01; respectively). Within domains, the head and neck cancer subscale score did not differ from baseline to EOI (median 28.5 versus 27.0, P = 0.69), but significantly worsened from EOI to EOCRT (27.0 versus 9.5, P < 0.01). Swallowing, oral pain and voice quality improved from baseline to EOI, but worsened from EOI to EOCRT. Physical and functional scores worsened from baseline to EOI and from EOI to EOCRT. The emotional well-being score improved from baseline to EOI but worsened from EOI to EOCRT.ConclusionsOverall, HRQOL did not significantly change from baseline to EOI but dramatically worsened from EOI to EOCRT.