Stereotactic Body Radiation Therapy (SBRT) for Hepatocellular Carcinoma (HCC) With Single Photon Emission Computed Tomography (SPECT) Functional Treatment Planning in Patients With Advanced Hepatic Cirrhosis.

Purpose: We report on the feasibility and outcomes of liver stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) with single-photon emission computed tomography (SPECT) functional treatment planning in patients with Child-Pugh (CP) B/C cirrhosis. Methods and Materials: Liver SPECT with 99mTc-sulfur colloid was coregistered to treatment planning computed tomography (CT) for the guided avoidance of functional hepatic parenchyma during SBRT. Functional liver volumes (FLVs) obtained from SPECT were compared with anatomic liver volumes defined on the planning CT. Radiation dose constraints were adapted exclusively to FLV. Local control, toxicity, and survival were reported with at least 6 months of radiographic follow-up. Pre- and posttransplant outcomes were analyzed in a subset of patients who completed SBRT as a bridge to liver transplant. Model of End-Stage Liver Disease was used to score hepatic function before and after SBRT completion. Results: With a median follow-up of 32 months, 45 patients (58 lesions) with HCC and CP-B/C cirrhosis received SBRT to a median dose of 45 Gy (3-5 fractions). FLV loss (34%, P < .001) was observed in all patients, and the functional and anatomic liver volumes matched well in a control group of noncirrhotic/non-HCC patients. Despite marked functional parenchyma retraction, the amount of FLV on SPECT exposed to the threshold irradiation was significantly less than the CT liver volumes (P < .001) because of the optimized beam placement during dosimetry planning. Twenty-three patients (51%) successfully completed orthotopic liver transplant, with a median time to transplant of 9.2 months. With 91% in-field local control, the overall 2-year survival was 65% (90% after the orthotopic liver transplant), with no incidence of radiation-induced liver disease observed within 3 to 4 months or accelerated CP class migration from B to C within the first 6 months post-SBRT. Mean Model of End-Stage Liver Disease-Na score was not significantly elevated at 3-month intervals after SBRT completion. Conclusions: Functional treatment planning with 99mTc sulfur colloid SPECT/CT allows identification and avoidance of functional hepatic parenchyma in patients with CP-B/C cirrhosis, leading to low toxicity and satisfactory transplant outcomes.

Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial.

BACKGROUND: Primary adrenal insufficiency (PAI) mortality and morbidity remain unacceptably high, possibly arising as glucocorticoid replacement does not replicate natural physiology. A pulsatile subcutaneous pump can closely replicate cortisol's circadian and ultradian rhythm. OBJECTIVES: To assess the effect of pump therapy on quality of life, mood, functional neuroimaging, behavioural/cognitive responses, sleep and metabolism. METHODS: A 6-week randomised, crossover, double-blinded and placebo-controlled feasibility study of usual dose hydrocortisone in PAI administered as either pulsed subcutaneous or standard care in Bristol, United Kingdom (ISRCTN67193733). Participants were stratified by adrenal insufficiency type. All participants who received study drugs are included in the analysis. The primary outcome, the facial expression recognition task (FERT), occurred at week 6. RESULTS: Between December 2014 and 2017, 22 participants were recruited - 20 completed both arms, and 21 were analysed. The pump was well-tolerated. No change was seen in the FERT primary outcome; however, there were subjective improvements in fatigue and mood. Additionally, functional magnetic resonance imaging revealed differential neural processing to emotional cues and visual stimulation. Region of interest analysis identified the left amygdala and insula, key glucocorticoid-sensitive regions involved in emotional ambiguity. FERT post hoc analysis confirmed this response. There were four serious adverse events (AE): three intercurrent illnesses requiring hospitalisation (1/3, 33.3% pump) and a planned procedure (1/1, 100% pump). There was a small number of expected AEs: infusion site bruising/itching (3/5, 60% pump), intercurrent illness requiring extra (3/7, 42% pump) and no extra (4/6, 66% pump) steroid. CONCLUSIONS: These findings support the administration of hormone therapy that mimics physiology.

Surveillance and treatment of primary hepatocellular carcinoma (aka. STOP HCC): protocol for a prospective cohort study of high-risk patients for HCC using GALAD-score.

BACKGROUND: Vietnam and Saudi Arabia have high disease burden of primary hepatocellular carcinoma (HCC). Early detection in asymptomatic patients at risk for HCC is a strategy to improve survival outcomes in HCC management. GALAD score, a serum-based panel, has demonstrated promising clinical utility in HCC management. However, in order to ascertain its potential role in the surveillance of the early detection of HCC, GALAD needs to be validated prospectively for clinical surveillance of HCC (i.e., phase IV biomarker validation study). Thus, we propose to conduct a phase IV biomarker validation study to prospectively survey a cohort of patients with advanced fibrosis or compensated cirrhosis, irrespective of etiologies, using semi-annual abdominal ultrasound and GALAD score for five years. METHODS: We plan to recruit a cohort of 1,600 patients, male or female, with advanced fibrosis or cirrhosis (i.e., F3 or F4) and MELD ≤ 15, in Vietnam and Saudi Arabia (n = 800 each). Individuals with a liver mass ≥ 1 cm in diameter, elevated alpha-fetoprotein (AFP) (≥ 9 ng/mL), and/or elevated GALAD score (≥ -0.63) will be scanned with dynamic contrast-enhanced magnetic resonance imaging (MRI), and a diagnosis of HCC will be made by Liver Imaging Reporting and Data System (LiRADS) assessment (LiRADS-5). Additionally, those who do not exhibit abnormal imaging findings, elevated AFP titer, and/or elevated GALAD score will obtain a dynamic contrast-enhanced MRI annually for five years to assess for HCC. Only MRI nearest to the time of GALAD score measurement, ultrasound and/or AFP evaluation will be included in the diagnostic validation analysis. MRI will be replaced with an abdominal computed tomography scan when MRI results are poor due to patient conditions such as movement etc. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI will not be carried out in study sites in both countries. Bootstrap resampling technique will be used to account for repeated measures to estimate standard errors and confidence intervals. Additionally, we will use the Cox proportional hazards regression model with covariates tailored to the hypothesis under investigation for time-to-HCC data as predicted by time-varying biomarker data. DISCUSSION: The present work will evaluate the performance of GALAD score in early detection of liver cancer. Furthermore, by leveraging the prospective cohort, we will establish a biorepository of longitudinally collected biospecimens from patients with advanced fibrosis or cirrhosis to be used as a reference set for future research in early detection of HCC in the two countries. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov Registration date: 22 April 2022 Trial registration number: NCT05342350 URL of trial registry record.

Hospital-physician Integration and Value-based Payment: Early Results From MIPS.

BACKGROUND: Hospital-physician integration is often justified as a driver of clinical quality improvement due to joint resources covering a broad spectrum of care. Value-based programs, such as the Medicare Merit-Based Incentive Payment System (MIPS), are intended to tie financial incentives to clinical quality, which may confer an advantage on such integrated practices. OBJECTIVES: We assessed the relationship between hospital-physician integration and MIPS performance by comparing hospital-integrated practices and independent practices. RESEARCH DESIGN: This was a cross-sectional study using data from the Quality Payment Program for the performance year 2020. SUBJECTS: Physician practices with a valid MIPS composite score in performance year 2020. MEASURES: Hospital integration was based on whether at least 75% of a practice's physicians either billed most of their services using hospital outpatient department codes or billed through a hospital tax identifier. The primary outcome was the MIPS quality category score, and the secondary outcomes were the specific quality measures reported by practice groups. RESULTS: Of the 20 most frequently reported measures, 14 were common in both groups. No difference was observed in the quality category score between hospital-integrated practices and independent practices in either unadjusted comparisons or after adjusting for practice characteristics, including practice size, geography, specialty mix, and case mix. In the secondary outcome models for specific quality measures, hospital-integrated practices achieved higher scores on most overlap measures but not all. CONCLUSIONS: The findings on quality category score suggest that hospital integration does not confer much advantage in the context of MIPS quality performance.

Dysfunction of basal ganglia functional connectivity associated with subjective and cognitive fatigue in multiple sclerosis.

Objectives: Central fatigue is one of the most common symptoms in multiple sclerosis (MS). It has a profound impact on quality of life and a negative effect on cognition. Despite its widespread impact, fatigue is poorly understood and very difficult to measure. Whilst the basal ganglia has been implicated in fatigue the nature of its role and involvement with fatigue is still unclear. The aim of the present study was to establish the role of the basal ganglia in MS fatigue using functional connectivity measures. Methods: The present study examined the functional connectivity (FC) of the basal ganglia in a functional MRI study with 40 female participants with MS (mean age = 49.98 (SD = 9.65) years) and 40 female age-matched (mean age = 49.95 (SD = 9.59) years) healthy controls (HC). To measure fatigue the study employed the subjective self-report Fatigue Severity Scale and a performance measure of cognitive fatigue using an alertness-motor paradigm. To distinguish physical and central fatigue force measurements were also recorded. Results: The results suggest that decreased local FC within the basal ganglia plays a key role in cognitive fatigue in MS. Increased global FC between the basal ganglia and the cortex may sub serve a compensatory mechanism to reduce the impact of fatigue in MS. Conclusion: The current study is the first to show that basal ganglia functional connectivity is associated with both subjective and objective fatigue in MS. In addition, the local FC of the basal ganglia during fatigue inducing tasks could provide a neurophysiological biomarker of fatigue.

Fidelity of 3D Printed Brains from MRI Scan in Children with Pathology (Prior Hypoxic Ischemic Injury).

Cortical injury on the surface of the brain in children with hypoxic ischemic injury (HII) can be difficult to demonstrate to non-radiologists and lay people using brain images alone. Three-dimensional (3D) printing is helpful to communicate the volume loss and pathology due to HII in children's brains. 3D printed models represent the brain to scale and can be held up against models of normal brains for appreciation of volume loss. If 3D printed brains are to be used for formal communication, e.g., with medical colleagues or in court, they should have high fidelity of reproduction of the actual size of patients' brains. Here, we evaluate the size fidelity of 3D printed models from MRI scans of the brain, in children with prior HII. Twelve 3D prints of the brain were created from MRI scans of children with HII and selected to represent a variety of cortical pathologies. Specific predetermined measures of the 3D prints were made and compared to measures in matched planes on MRI. Fronto-occipital length (FOL) and bi-temporal/bi-parietal diameters (BTD/BPD) demonstrated high interclass correlations (ICC). Correlations were moderate to weak for hemispheric height, temporal height, and pons-cerebellar thickness. The average standard error of measurement (SEM) was 0.48 cm. Our results demonstrate high correlations in overall measurements of each 3D printed model derived from brain MRI scans versus the original MRI, evidenced by high ICC values for FOL and BTD/BPD. Measures with low correlation values can be explained by variability in matching the plane of measurement to the MRI slice orientation.

Autologous Islet Transplantation After Total Pancreatectomy in a Patient Recovered from SARS-CoV-2: A Case Report.

BACKGROUND SARS-CoV-2 infection or COVID-19 disease has been linked to the onset of diabetes and metabolic dysregulation because it has been suggested that viral entry proteins, specifically ACE2 and TMPRSS2, are expressed in the exocrine cells and ductal epithelium of the pancreas. Because of the unknown effect this can have on islet function, there can be doubt that patients with previous SARS-CoV-2 infections are good candidates for autologous islet transplantation after total pancreatectomy (TPAIT). CASE REPORT A patient with a history of chronic pancreatitis and previous non-surgical interventions was presented as a viable candidate for TPAIT at our institution. Approximately 1 month later, the patient contracted a SARS-CoV-2 infection, resulting in a mild case of COVID-19. The infection resolved without the need for hospitalization. At the time of this occurrence, COVID-19 was primarily considered a respiratory ailment, and little was known of the potential association between metabolic dysfunction and SARS-CoV-2. Islet isolation and surgery proceeded in a textbook manner with no surgical complications. The patient was weaned off exogenous insulin within 3 months after transplantation. CONCLUSIONS Favorable outcomes after surgery included pain reduction, islet function, and improved quality of life for the patient in the first 6 months after the procedure. These successful results demonstrate that SARS-CoV-2 infection did not prevent the patient from achieving good glucose regulation after auto-islet transplantation. This outcome suggests that, at least in this instance of mild infection, there were no long-lasting negative COVID-19-associated effects on the transplanted islets that might impact islet function.

Voxel-based map of the inter-arterial watershed zones in children.

PURPOSE: To create a voxel-based map of the inter-arterial watershed derived from children who have sustained a hypoxic-ischemic injury involving this region at term. MATERIALS AND METHODS: Patients 0-18 years of age diagnosed with a hypoxic-ischemic injury of the watershed on magnetic resonance imaging (MRI) were included. Two pediatric neuroradiologists segmented the lesions as visualized on the T2-weighted sequence. All lesion maps were normalized to a brain template and overlapped to create a frequency map in order to highlight the frequency of involvement of portions of the cortical watershed. RESULTS: A total of 47 patients (35 boys) were included in the final sample. Their mean age was 7.6 ± 3.6 years. The cortical watershed was successfully mapped. Three watershed regions were defined: the anterior, peri-Sylvian, and posterior watershed zones. The anterior and peri-Sylvian watershed zones are connected through the involvement of the middle frontal gyrus. The peri-Sylvian and the posterior watershed zones are connected through the involvement of the inferior parietal lobule, the posterior aspect of the superior temporal gyrus, and the angular gyrus with the occipital lobe. The temporal lobe and orbital part of the frontal lobe are largely spared in all patients. CONCLUSION: A voxel-based lesion map of children with watershed hypoxic ischemic injury at term was created and three inter-arterial watershed zones defined: anterior, peri-Sylvian, and posterior watersheds.

Safety and efficacy of losartan for the reduction of brain atrophy in clinically diagnosed Alzheimer's disease (the RADAR trial): a double-blind, randomised, placebo-controlled, phase 2 trial.

BACKGROUND: Drugs modifying angiotensin II signalling could reduce Alzheimer's disease pathology, thus decreasing the rate of disease progression. We investigated whether the angiotensin II receptor antagonist losartan, compared with placebo, could reduce brain volume loss, as a measure of disease progression, in clinically diagnosed mild-to-moderate Alzheimer's disease. METHODS: In this double-blind, multicentre, randomised controlled trial, eligible patients aged 55 years or older, previously untreated with angiotensin II drugs and diagnosed (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria) with mild-to-moderate Alzheimer's disease, and who had capacity to consent, were recruited from 23 UK National Health Service hospital trusts. After undergoing a 4-week, open-label phase of active treatment then washout, participants were randomly assigned (1:1) oral over-encapsulated preparations of either 100 mg losartan (after an initial two-dose titration stage) or matched placebo daily for 12 months. Randomisation, minimised by age and baseline medial temporal lobe atrophy score, was undertaken online or via pin-access service by telephone. Participants, their study companions, and study personnel were masked to group assignment. The primary outcome, analysed by the intention-to-treat principle (ie, participants analysed in the group to which they were randomised, without imputation for missing data), was change in whole brain volume between baseline and 12 months, measured using volumetric MRI and determined by boundary shift interval (BSI) analysis. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN93682878) and the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT 2012-003641-15), and is completed. FINDINGS: Between July 22, 2014, and May 17, 2018, 261 participants entered the open-label phase. 211 were randomly assigned losartan (n=105) or placebo (n=106). Of 197 (93%) participants who completed the study, 171 (81%) had complete primary outcome data. The mean brain volume (BSI) reduction was 19·1 mL (SD 10·3) in the losartan group and 20·0 mL (10·8) in the placebo group. The difference in total volume reduction between groups was -2·29 mL (95% CI -6·46 to 0·89; p=0·14). The number of adverse events was low (22 in the losartan group and 20 in the placebo group) with no differences between treatment groups. There was one treatment-related death per treatment group. INTERPRETATION: 12 months of treatment with losartan was well tolerated but was not effective in reducing the rate of brain atrophy in individuals with clinically diagnosed mild-to-moderate Alzheimer's disease. Further research is needed to assess the potential therapeutic benefit from earlier treatment in patients with milder cognitive impairment or from longer treatment periods. FUNDING: Efficacy and Mechanism Evaluation Programme (UK Medical Research Council and National Institute for Health Research).

Is Continuing Anticoagulation or Antiplatelet Therapy Safe Prior to Kidney Transplantation?

BACKGROUND Patients undergoing kidney transplantation are often placed on anticoagulation or antiplatelet therapy, and their perioperative management is often challenging. This study aimed to determine the safety of continuing anticoagulation or antiplatelet therapy prior to kidney transplantation. The primary outcome was bleeding after transplantation. MATERIAL AND METHODS Patients who underwent kidney transplantation between January 2017 and July 2019 were included and divided into 3 groups: pretransplant anticoagulation with warfarin (WARF; n=23); pretransplant antiplatelet therapy with clopidogrel/aspirin (ASA/CLOP; n=32); and control (CTL; n=197). Patients received kidneys from live or deceased donors. Preoperative INRs and platelet counts were compared to ensure therapeutic anticoagulation in the warfarin group and no significant platelet count variation among groups. The primary outcome was graft exploration for bleeding at 3 and 6 months after transplantation. Secondary outcomes included perioperative transfusion requirements, prolonged length of stay (>7 days), and outcomes at 3 and 6 months after transplantation, including hemodialysis and rejection rates and creatinine levels. RESULTS Pretransplant INR was significantly greater in the warfarin group (CTL 1.1, WARF 2.2, ASA/CLOP 1.2; P<0.01). There were no differences in pretransplant platelet count (CTL 202×10³, WARF 186×10³, ASA/CLOP 194×10³; P=0.31), graft exploration for bleeding at 3 (CTL 3%, WARF 0%, ASA/CLOP 3%; P=0.69) and 6 months after transplantation (CTL 1%, WARF 4%, ASA/CLOP 0%; P=0.12), or perioperative blood transfusion requirements (CTL 4%, WARF 4%, ASA/CLOP 14%; P=0.13). Prolonged length of stay was similar (CTL 24%, WARF 26%, ASA/CLOP 44%; P=0.08). There were no significant differences among groups at 3 months in dialysis (CTL 2%, WARF 0%, ASA/CLOP 0%; P=0.71), creatinine (CTL 1.5 mg/dL, WARF 1.7 mg/dL, ASA/CLOP 1.7; P=0.13), or rejection (CTL 6%, WARF 0%, ASA/CLOP 0%) or at 6 months in dialysis (CTL 3%, WARF 0%, ASA/CLOP 0%; P=0.49), creatinine (CTL 1.5 mg/dL, WARF 1.7 mg/dL, ASA/CLOP 1.5; P=0.49), or rejection (CTL 1%, WARF 0%, ASA/CLOP 3%). CONCLUSIONS Continuing anticoagulation or antiplatelet was safe in not increasing bleeding complications or perioperative transfusion requirements. Outcomes were similar at 3 and 6 months among groups. This strategy avoids exposing patients to risk of thrombosis if treatment is held and simplifies proceeding to transplantation.

A rare Fusarium equiseti infection in a 53-year-old male with burn injury: A case report.

BACKGROUND AND PURPOSE: Burn injuries are prone to infection caused by bacteria, fungi, or other pathogens. Fungal wound infection usually has non-specific clinical symptoms. Nevertheless, in some cases, the fungal burden is so substantial that can easily be seen by the naked eyes, but this phenomenon has rarely been reported with Fusarium. CASE REPORT: A 53-year-old patient with severe burn injury was admitted to the intensive care unit of the National Hospital of Burn, Ha Noi, Vietnam. His wound was dressed with a traditional herbal product before the hospital admission. On the 5th day after the admission, some white patches suspected of fungal colonies appeared on burn lesions where the herbal medicine was placed. Histological examination (Periodic acid-Schiff) and culture of biopsy samples taken from those lesions revealed fungus that was identified as Fusarium equiseti after analysis of the internal transcribed spacer and D1/D2 region of the large subunit of the 28S rDNA. The isolated strain showed susceptibility to voriconazole but resistance to fluconazole, itraconazole, caspofungin, and amphotericin B in vitro. The patient received aggressive treatment, including IV voriconazole (400 mg daily from day five); however, he could not recover. CONCLUSION: Fusarium should be suspected in burn patients with white patches on lesions. Antifungal susceptibility testing is important since multidrug resistance is common among Fusarium strains.

Species Distribution and Antifungal Susceptibility Pattern of Candida Recovered from Intensive Care Unit Patients, Vietnam National Hospital of Burn (2017-2019).

INTRODUCTION: Candida species is the most common cause of invasive fungal infection. With the wide variation in species distribution and antifungal susceptibility of causative agents, local epidemiological profiles are needed to provide effective guidelines for the treatment of invasive candidiasis. OBJECTIVE: To find out the species distribution and antifungal susceptibilities of Candida strains isolated from patients in an intensive care unit (ICU) of Vietnam. METHODS: All patients in ICU of Vietnam National Hospital of Burn with Candida isolation reported from January 2017 to December 2019 were retrospectively studied. Species identification and antifungal susceptibility testing were performed using VITEK 2 Compact. The identification was reconfirmed by sequencing of the internal transcribed spacer regions when needed. RESULTS: A total of 186 yeasts belonging to ten species were collected. The most common agent was C. tropicalis (45.7%), followed by C. albicans (42.4%), and C. parapsilosis (7.53%). The isolated yeasts showed less susceptibility to fluconazole (resistant rate R 10.7%) than to micafungin, caspofungin, flucytosine and amphotericin B (R 0%, 0.6%, 2.3% and 3.4%, respectively, p < 0.05). C. albicans isolates were more susceptible to fluconazole (R 5.2%) than C. tropicalis (R 15.7%). Resistance to voriconazole was seen only among C. albicans (3.9%) and C. tropicalis isolates (9.9%). CONCLUSION: Non-albicans species (especially C. tropicalis) is the predominant species, and there is a significant proportion of isolates with reduced susceptibility to azole but not to echinocandin.

Hospital Employment Of Physicians In Massachusetts Is Associated With Inappropriate Diagnostic Imaging.

The transition among many US physicians from independent practice to hospital employment has raised concerns about whether employed physicians will be more inclined to refer patients for hospital-based services that are unnecessary or inappropriate. Using claims data for 2009-16, we conducted a difference-in-differences analysis to investigate whether this form of hospital-physician integration is associated with inappropriate referrals for magnetic resonance imaging (MRI), a widely used mode of diagnostic imaging, for three common medical conditions: lower back pain, knee pain, and shoulder pain. Study findings indicate that the odds of a patient receiving an inappropriate MRI referral increased by more than 20 percent after a physician transitioned to hospital employment. Most patients who received an MRI referral by an employed physician obtained the procedure at the hospital where the referring physician was employed. These results point to hospital-physician integration as a potential driver of low-value care.

Protein Phosphatase Type 2C Functions in Phytohormone-Dependent Pathways and in Plant Responses to Abiotic Stresses.

Plants, as sessile organisms, are susceptible to a myriad of stress factors, especially abiotic stresses. Over the course of evolution, they have developed multiple mechanisms to sense and transduce environmental stimuli for appropriate responses. Among those, phosphorylation and dephosphorylation, regulated by protein kinases and protein phosphatases, respectively, are considered crucial signal transduction mechanisms. Regarding the latter group, protein phosphatases type 2C (PP2Cs) represent the largest division of PPs. In addition, the discovery of regulatory functions of PP2Cs in the abscisic acid (ABA)-signaling pathway, the major signal transduction pathway in abiotic stress responses, indicates the significant importance of PP2C members in plant adaptation to adverse environmental factors. In this review, current understanding of the roles of PP2Cs in different phytohormone-dependent pathways related to abiotic stress is summarized, highlighting the crosstalk between the ABA-signaling pathway with other hormonal pathways via certain ABA-related PP2Cs. We also updated the progress of in planta characterization studies of PP2Cs under abiotic stress conditions, providing knowledge of PP2C manipulation in developing abiotic stress-tolerant crops.

Glucocorticoid ultradian rhythmicity differentially regulates mood and resting state networks in the human brain: A randomised controlled clinical trial.

Adrenal glucocorticoid secretion into the systematic circulation is characterised by a complex rhythm, composed of the diurnal variation, formed by changes in pulse amplitude of an underlying ultradian rhythm of short duration hormonal pulses. To elucidate the potential neurobiological significance of glucocorticoid pulsatility in man, we have conducted a randomised, double-blind, placebo-controlled, three-way crossover clinical trial on 15 healthy volunteers, investigating the impact of different glucocorticoid rhythms on measures of mood and neural activity under resting conditions by recruiting functional neuroimaging, computerised behavioural tests and ecological momentary assessments. Endogenous glucocorticoid biosynthesis was pharmacologically suppressed, and plasma levels of corticosteroid restored by hydrocortisone replacement in three different regimes, either mimicking the normal ultradian and circadian profile of the hormone, or retaining the normal circadian but abolishing the ultradian rhythm of the hormone, or by our current best oral replacement regime which results in a suboptimal circadian and ultradian rhythm. Our results indicate that changes in the temporal mode of glucocorticoid replacement impact (i) the morning levels of self-perceived vigour, fatigue and concentration, (ii) the diurnal pattern of mood variation, (iii) the within-network functional connectivity of various large-scale resting state networks of the human brain, (iv) the functional connectivity of the default-mode, salience and executive control networks with glucocorticoid-sensitive nodes of the corticolimbic system, and (v) the functional relationship between mood variation and underlying neural networks. The findings indicate that the pattern of the ultradian glucocorticoid rhythm could affect cognitive psychophysiology under non-stressful conditions and opens new pathways for our understanding on the neuropsychological effects of cortisol pulsatility with relevance to the goal of optimising glucocorticoid replacement strategies.

Accuracy of radiologists, nonradiologists, and laypeople for identifying children with cerebral cortical atrophy from "Mercator map" curved reconstructions of MRIs of the brain.

BACKGROUND: Using text reports to communicate bilateral, symmetric, and zonal cortical brain atrophy in children with term hypoxic ischemic injury (HII) to parents and legal professionals contesting compensation rights can be difficult. Using standard cross-sectional images for explaining bilateral, regional brain imaging to laypeople is also challenging. A single flattened image of the brain surface, much like a map of the earth is derived from a globe, can be generated from curved reconstruction of magnetic resonance imaging (MRI) scans, i.e., a Mercator map. Laypeople's ability to identify abnormal "Mercator brain maps," without prior training, requires evaluation before use in nonmedical settings. AIM: To determine the sensitivity and specificity of laypeople in detecting abnormal pediatric Mercator flat-earth maps of the brain, without prior training. METHODS AND MATERIALS: 10 Mercator brain maps were provided to 111 participants individually. The maps comprised 5 HII, 1 cortical dysplasia, and 4 normal cases. Participants were required to identify the abnormal scans. Sensitivity and specificity overall and for participants' subgroups were calculated. RESULTS: Overall sensitivity and specificity were 67% and 80%, respectively. General radiologists (n = 12) had sensitivity and specificity of 91.2% and 94.6%, respectively. Laypeople (n = 54) had a sensitivity of 67% and specificity of 80%. CONCLUSION: The high specificity and sensitivity of radiologists validated the technique for distinguishing abnormal scans, regarding cortical pathology. High specificity of laypeople for identifying abnormal brains using Mercator maps indicates that this is a viable communication tool for demonstrating cortical MRI abnormalities of HII in children to laypersons.

Using structural and functional MRI as a neuroimaging technique to investigate chronic fatigue syndrome/myalgic encephalopathy: a systematic review.

OBJECTIVE: This systematic review aims to synthesise and evaluate structural MRI (sMRI) and functional MRI (fMRI) studies in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). METHODS: We systematically searched Medline and Ovid and included articles from 1991 (date of Oxford diagnostic criteria for CFS/ME) to first April 2019. Studies were selected by predefined inclusion and exclusion criteria. Two reviewers independently reviewed the titles and abstracts to determine articles for inclusion, full text and quality assessment for risk of bias. RESULTS: sMRI studies report differences in CFS/ME brain anatomy in grey and white matter volume, ventricular enlargement and hyperintensities. Three studies report no neuroanatomical differences between CFS/ME and healthy controls. Task-based fMRI investigated working memory, attention, reward and motivation, sensory information processing and emotional conflict. The most consistent finding was CFS/ME exhibited increased activations and recruited additional brain regions. Tasks with increasing load or complexity produced decreased activation in task-specific brain regions. CONCLUSIONS: There were insufficient data to define a unique neural profile or biomarker of CFS/ME. This may be due to inconsistencies in finding neuroanatomical differences in CFS/ME and the variety of different tasks employed by fMRI studies. But there are also limitations with neuroimaging. All brain region specific volumetric differences in CFS/ME were derived from voxel-based statistics that are biased towards group differences that are highly localised in space. fMRI studies demonstrated both increases and decreases in activation patterns in CFS/ME, this may be related to task demand. However, fMRI signal cannot differentiate between neural excitation and inhibition or function-specific neural processing. Many studies have small sample sizes and did not control for the heterogeneity of this clinical population. We suggest that with robust study design, subgrouping and larger sample sizes, future neuroimaging studies could potentially lead to a breakthrough in our understanding of the disease.

A Rare Case of Fungal Burn Wound Infection Caused by Fusarium solani in Vietnam.

A patient with extensive burn injuries was admitted to the National Hospital of Burns in Hanoi, Vietnam, and diagnosed with fungal wound infection by histological examination of skin biopsy samples. Fusarium solani was isolated and identified by analysis of its morphological features and the sequence of the internal transcribed spacer region. The isolation showed in vitro resistant to fluconazole, voriconazole, itraconazole, amphotericin B, and caspofungin. Invasive fusariosis is difficult to treat due to its angioinvasive property and its lacking amenability to treatment with antifungal drugs. This infection is rare and has not been reported so far in Vietnam.