Influence of Eat, Sleep, and Console on Infants Pharmacologically Treated for Opioid Withdrawal: A Post Hoc Subgroup Analysis of the ESC-NOW Randomized Clinical Trial.

Importance: The function-based eat, sleep, console (ESC) care approach substantially reduces the proportion of infants who receive pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). This reduction has led to concerns for increased postnatal opioid exposure in infants who receive pharmacologic treatment. However, the effect of the ESC care approach on hospital outcomes for infants pharmacologically treated for NOWS is currently unknown. Objective: To evaluate differences in opioid exposure and total length of hospital stay (LOS) for pharmacologically treated infants managed with the ESC care approach vs usual care with the Finnegan tool. Design, Setting, and Participants: This post hoc subgroup analysis involved infants pharmacologically treated in ESC-NOW, a stepped-wedge cluster randomized clinical trial conducted at 26 US hospitals. Hospitals maintained pretrial practices for pharmacologic treatment, including opioid type, scheduled opioid dosing, and use of adjuvant medications. Infants were born at 36 weeks' gestation or later, had evidence of antenatal opioid exposure, and received opioid treatment for NOWS between September 2020 and March 2022. Data were analyzed from November 2022 to January 2024. Exposure: Opioid treatment for NOWS and the ESC care approach. Main Outcomes and Measures: For each outcome (total opioid exposure, peak opioid dose, time from birth to initiation of first opioid dose, length of opioid treatment, and LOS), we used generalized linear mixed models to adjust for the stepped-wedge design and maternal and infant characteristics. Results: In the ESC-NOW trial, 463 of 1305 infants were pharmacologically treated (143/603 [23.7%] in the ESC care approach group and 320/702 [45.6%] in the usual care group). Mean total opioid exposure was lower in the ESC care approach group with an absolute difference of 4.1 morphine milligram equivalents per kilogram (MME/kg) (95% CI, 1.3-7.0) when compared with usual care (4.8 MME/kg vs 8.9 MME/kg, respectively; P = .001). Mean time from birth to initiation of pharmacologic treatment was 22.4 hours (95% CI, 7.1-37.7) longer with the ESC care approach vs usual care (75.4 vs 53.0 hours, respectively; P = .002). No significant difference in mean peak opioid dose was observed between groups (ESC care approach, 0.147 MME/kg, vs usual care, 0.126 MME/kg). The mean length of treatment was 6.3 days shorter (95% CI, 3.0-9.6) in the ESC care approach group vs usual care group (11.8 vs 18.1 days, respectively; P < .001), and mean LOS was 6.2 days shorter (95% CI, 3.0-9.4) with the ESC care approach than with usual care (16.7 vs 22.9 days, respectively; P < .001). Conclusion and Relevance: When compared with usual care, the ESC care approach was associated with less opioid exposure and shorter LOS for infants pharmacologically treated for NOWS. The ESC care approach was not associated with a higher peak opioid dose, although pharmacologic treatment was typically initiated later. Trial Registration: ClinicalTrials.gov Identifier: NCT04057820.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial.

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

Ageing impairs the regenerative capacity of regulatory T cells in mouse central nervous system remyelination.

Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis, however, its efficiency declines with age. Regulatory T cells (Treg) recently emerged as critical players in tissue regeneration, including remyelination. However, the effect of ageing on Treg-mediated regenerative processes is poorly understood. Here, we show that expansion of aged Treg does not rescue age-associated remyelination impairment due to an intrinsically diminished capacity of aged Treg to promote oligodendrocyte differentiation and myelination in male and female mice. This decline in regenerative Treg functions can be rescued by a young environment. We identified Melanoma Cell Adhesion Molecule 1 (MCAM1) and Integrin alpha 2 (ITGA2) as candidates of Treg-mediated oligodendrocyte differentiation that decrease with age. Our findings demonstrate that ageing limits the neuroregenerative capacity of Treg, likely limiting their remyelinating therapeutic potential in aged patients, and describe two mechanisms implicated in Treg-driven remyelination that may be targetable to overcome this limitation.

Change in Cognitive Function over the Course of Major Depressive Disorder: A Systematic Review and Meta-analysis.

Major depressive disorder (MDD) is associated with significant cognitive deficits during the acute and remitted stages. The aim of this systematic review and meta-analysis was to examine the course of cognitive function whilst considering demographic, treatment, or clinical features of MDD that could moderate the extent of cognitive change. Databases were searched to identify studies that reported on cognitive function in MDD with a ≥12-week test-retest interval. Relevant studies were pooled using random effects modelling to generate an inverse-variance, weighted, mean effect size estimate (Hedges' g) of cognitive change for each cognitive variable and for an overall composite cognitive domain. Of 6898 records, 99 eligible studies were identified from which 69 were meta-analysed, consisting of 4639 MDD patients (agemean = 40.25 years, female% = 64.62%) across 44 cognitive variables. In over 95% of cognitive variables, improvements were either of non-significant, negligible, or of a small magnitude, and when compared to matched healthy controls, the possibility of practice effects could not be precluded. Depressive symptom improvement and the number of previous depressive episodes moderated the extent of cognitive change, demonstrating state- and scar-like features for one-quarter of the cognitive domains. Further longitudinal studies are required to elucidate the MDD cognitive trajectory from initial onset. Findings nonetheless suggest that following pharmacological and non-pharmacological treatment, cognitive change in MDD is typically small, but the capacity for change may be less with episode recurrence. Targeting cognition early in the course of illness may facilitate better prognosis and support a more complete functional recovery.

Development of a quantitative ELISA for SARS-CoV-2 vaccine candidate, NDV-HXP-S, with CpG 1018® adjuvant.

NDV-HXP-S is a Newcastle disease virus (NDV) vectored vaccine candidate which expresses the S-antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This vaccine candidate is under evaluation in human clinical studies with and without cytosine phosphate guanine (CpG) 1018® adjuvant. Existing potency methods for NDV-HXP-S do not allow for quantification of the S-antigen when the adjuvant is present. To support evaluation of NDV-HXP-S with CpG 1018® adjuvant, an inhibition enzyme-linked immunosorbent assay (ELISA) was developed to allow for quantification and stability assessments of the vaccine. A pilot 6-month stability study was conducted on NDV-HXP-S vaccine with and without CpG 1018® adjuvant under refrigerated conditions (2°C to 8°C) and accelerated stability testing conditions (40°C). The vaccine was mixed with and without CpG 1018® adjuvant in saline and maintained S-antigen content at 2°C to 8°C for the entire 6-month period. Additionally, a pilot controlled temperature chain (CTC) stability study was conducted at the completion of the 6-month study and demonstrated the possibility for this vaccine candidate to attain CTC stability labeling.

Best Practices for Promoting Safe Patient Care Delivery by Hospital-Based Traveling Clinical Staff: An Integrative Review.

BACKGROUND: Hospitals use traveling clinical staff (TCS) to fill personnel shortages. Although this approach may help improve staffing ratios, it is not without risk. PURPOSE: The interdisciplinary team conducted an integrative literature review to determine best practices for promoting safe patient care delivery by TCS. METHODS: Using the Johns Hopkins Evidence-Based Practice model, the authors performed an integrative literature review, including appraisal of quality, synthesis of themes, and best-evidence recommendations. RESULTS: The final synthesis included 16 articles. Evidence demonstrated the importance of preemployment screening, standardized onboarding and orientation, and optimizing the integration of TCS into the work environment. CONCLUSION: Hospitals should use these recommendations when incorporating TCS into their teams.

Recurrent Pleomorphic Xanthoastrocytoma Presenting With Diffuse Leptomeningeal Spread.

We report a case highlighting key clinical, CSF, and imaging findings of recurrent pleomorphic xanthoastrocytoma with leptomeningeal spread.

Spinal Meningeal Mass Lesion: A Rare Presentation of Primary Dural Follicular Lymphoma.

INTRODUCTION: The differential diagnosis of a spinal intradural extramedullary mass lesion is broad and includes meningioma, schwannoma, neurofibroma, leptomeningeal metastasis, and myxopapillary ependymoma. Though rare, lymphoma should be included in the differential diagnosis of a dural mass lesion. CASE REPORT: A 38-year-old man presented with back pain that progressed over 1 month with associated focal tenderness over his mid to lower thoracic spine. He developed intermittent numbness of the bilateral lower extremities, nuchal rigidity, difficulty sleeping, and night sweats. A magnetic resonance imaging of the thoracic spine demonstrated a dorsal intradural extramedullary enhancing lesion from T7 to T10 extending outside the spinal canal. Dural thickening across the entire circumference of the spinal cord was noted. Computed tomography (CT)-guided biopsy of the thoracic lesion was performed, and pathology was consistent with follicular lymphoma. Fluorodeoxyglucose positron emission tomography:CT demonstrated no systemic disease. Bone marrow biopsy was negative for malignancy. Symptoms resolved with dexamethasone therapy. He was treated with bendamustine and rituximab with follow-up positron emission tomography:CT 2 months later demonstrating a complete response. CONCLUSIONS: Lymphoma can rarely present as an isolated dural lesion and should be considered in the differential diagnosis of intradural extramedullary spinal mass lesions. Prompt diagnosis and initiation of treatment can lead to complete response and resolution of symptoms.

The 2022 Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference: Summary of abstract-based presentations.

The global nonprofit organization PATH hosted the third Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Washington, DC, on November 29 to December 1, 2022. With a combination of plenary sessions and posters, keynote presentations, and breakout workshops, the 2022 VASE Conference featured key updates on research related to the development of vaccines against neglected diarrheal pathogens including Shigella, enterotoxigenic Escherichia coli (ETEC), Campylobacter, and Salmonella. The presentations and discussions highlighted the significant impact of these diarrheal pathogens, particularly on the health of infants and young children in low- and middle-income countries, reflecting the urgent need for the development and licensure of new enteric vaccines. Oral and poster presentations at the VASE Conference explored a range of topics, including: the global burden and clinical presentation of disease, epidemiology, and the impact of interventions; the assessment of the value of vaccines against enteric pathogens; preclinical evaluations of vaccine candidates and models of enteric diseases; vaccine candidates in clinical trials and human challenge models; host parameters and genomics that predict responses to infection and disease; the application of new omics technologies for characterization of emerging pathogens and host responses; novel adjuvants, vaccine delivery platforms, and immunization strategies; and strategies for combination/co-administered vaccines. The conference agenda also featured ten breakout workshop sessions on topics of importance to the enteric vaccine field, which are summarized separately. This article reviews key points and highlighted research presented in each of the plenary conference sessions and poster presentations at the 2022 VASE Conference.

Defect engineering of 1T'MX2(M= Mo, W andX= S, Se) transition metal dichalcogenide-based electrocatalyst for alkaline hydrogen evolution reaction.

The alkaline electrolyzer (AEL) is a promising device for green hydrogen production. However, their energy conversion efficiency is currently limited by the low performance of the electrocatalysts for the hydrogen evolution reaction (HER). As such, the electrocatalyst design for the high-performance HER becomes essential for the advancement of AELs. In this work, we used both hydrogen (H) and hydroxyl (OH) adsorption Gibbs free energy changes as the descriptors to investigate the catalytic HER performance of 1T' transition metal dichalcogenides (TMDs) in an alkaline solution. Our results reveal that the pristine sulfides showed better alkaline HER performance than their selenide counterparts. However, the activities of all pristine 1T' TMDs are too low to dissociate water. To improve the performance of these materials, defect engineering techniques were used to design TMD-based electrocatalysts for effective HER activity. Our density functional theory results demonstrate that introducing single S/Se vacancy defects can improve the reactivities of TMD materials. Yet, the desorption of OH becomes the rate-determining step. Doping defective MoS2with late 3d transition metal (TM) atoms, especially Cu, Ni, and Co, can regulate the reactivity of active sites for optimal OH desorption. As a result, the TM-doped defective 1T' MoS2can significantly enhance the alkaline HER performance. These findings highlight the potential of defect engineering technologies for the design of TMD-based alkaline HER electrocatalysts.

First foods in a packaged world: Results from the COMMIT consortium to protect young child diets in Southeast Asia.

Although commercially produced complementary foods (CPCFs) are increasingly sold throughout Southeast Asia, concerns have been raised about CPCFs nutritional quality, labelling practices and the strength and scope of national CPCF regulations. The Consortium for Improving Complementary Foods in Southeast Asia (COMMIT), composed of UN agencies and civil society organizations, was formed to assess the nutrient gap in the diets of young children and the consumer, product and policy landscapes for CPCFs in seven Southeast Asian countries. Results from a nutrient gap assessment indicate that the diets of children aged 6-23 months are suboptimal and deficient in micronutrients. A consumer survey revealed that caretakers commonly use CPCFs, are conscious of the importance of nutrition and are influenced by label claims. Results from a CPCF benchmarking showed that many products sold in Southeast Asia contained added sugar or sweeteners, had a high total sugar and/or high sodium content and that no CPCF product adhered to all recommended labelling practices. Further, a legal review of national binding legal measures relevant to CPCFs showed minimal alignment with available global guidance. Urgent actions are necessary to strengthen national regulations related to CPCF nutrient composition and labelling practices. To speed progress, COMMIT developed a compendium of existing standards and global guidance to help countries align their national regulations with CPCF composition, labelling and production recommendations. Advocacy to garner public support for new or improved CPCF regulations, as well as strong government monitoring and enforcement of regulations, is crucial to support efforts to safeguard and improve the diets of older infants and young children in Southeast Asia.

Benchmarking the nutrient composition and labelling practices of dry or instant cereals for older infants and young children across seven Southeast Asian countries.

In Southeast Asia, the increasing availability of commercially produced complementary foods (CPCF), including dry or instant cereals (CPCF cereals), has been noted, however, concerns exist around their nutrient profile and labelling practices. This 2021 study assessed the nutrient composition, labelling practices, and micronutrient content of CPCF cereals sold in the capital cities of seven Southeast Asian countries: Phnom Penh (Cambodia), Jakarta (Indonesia), Manila (Philippines), Bangkok (Thailand), Vientiane (Lao PDR), Hanoi (Vietnam), and Kuala Lumpur (Malaysia). The study adapted a nutrient profiling model from the WHO Regional Office for Europe to determine the proportion of products suitable for promotion for older infants and young children. Micronutrient content of fortified CPCF cereals was assessed against fortification levels specified in the Codex Alimentarius guideline for formulated complementary foods. Of the 484 products assessed, 184 (38.0%) met all nutrient composition requirements. Around one-third of CPCF cereals contained added sugars and/or sweeteners (37.2%) and high levels of sodium (28.9%). None of the CPCF cereals met all labelling requirements, primarily due to the presence of inappropriate claims on the labels. Most fortified CPCF cereals contained adequate amounts of critical micronutrients, such as calcium, iron, zinc, vitamin A, and vitamin D. However, rates of fortification varied across the seven countries, and almost a third (30.8%) of CPCF cereals were not fortified with any micronutrients. To support the appropriate promotion of CPCF in the region, Southeast Asian countries need to strengthen and enforce national binding legal measures, including national standards for the composition, labelling, and fortification of CPCF cereals.

Benchmarking the nutrient composition and labelling practices of commercially produced ready-to-eat purées and meals for older infants and young children across seven Southeast Asian countries.

Commercially produced complementary foods (CPCF), including ready-to-eat CPCF purées and meals, are gaining popularity among caregivers of older infants and young children (IYC) as a convenient alternative to home-prepared foods in low and middle-income countries. However, there is growing concern regarding the suitability of these products for older IYC, as they can contain high levels of sugar and/or sodium. Given the rapidly evolving market in Southeast Asia, it is crucial to monitor the appropriate composition and promotion of CPCF in the region. This study examined the nutrient composition and labelling practices of CPCF purées and meals sold in 2021 in the capital cities of seven Southeast Asian countries: Phnom Penh (Cambodia), Jakarta (Indonesia), Manila (Philippines), Bangkok (Thailand), Vientiane (Lao PDR), Hanoi (Viet Nam), Kuala Lumpur (Malaysia). The study adapted a nutrient profiling model from the WHO Regional Office for Europe to determine the proportion of products suitable for promotion for older IYC. The proportion of CPCF purées and meals that would require a high sugar front-of-pack warning based on the percentage energy from total sugar was also determined. Of the 459 CPCF purées/meals assessed, only 37.7% of the products met all nutrient composition requirements and none met all labelling requirements. In addition, most CPCF purées and meals were identified as having high total sugar content. To ensure that older IYC consume appropriate CPCF products, Southeast Asian countries need to implement and enforce regulations concerning the nutrient composition and labelling practices of CPCF purées and meals.

Micronutrient gaps during the complementary feeding period in seven countries in Southeast Asia: A Comprehensive Nutrient Gap Assessment.

The complementary feeding period is a critical stage of child development when micronutrient needs are high and challenging to meet. Understanding if specific micronutrient gaps exist during this period is critical for effective programming. A Comprehensive Nutrient Gap Assessment (CONGA) was conducted in seven countries in Southeast Asia to estimate gaps in micronutrients commonly lacking in the diets of children aged 6-23 months and to establish the certainty of available evidence for each identified gap. Sixty-eight evidence sources were identified during this analysis, and 310 micronutrient-specific data points were identified across all seven countries. Data points varied in recency, representativeness and evidence type. The CONGA methodology enabled the estimation of a gap burden rating for each micronutrient in each country, as well as a rating of their evidence certainty. Micronutrient gaps were identified in vitamin D, zinc and iron and a potential gap was identified in calcium during the complementary feeding period in the region. Evidence relevant to intake and deficiency of folate, vitamin B12 , thiamine, niacin, vitamin C and vitamin B6 was limited across the region. Proven strategies to address these gaps include increasing the availability and consumption of nutrient-dense foods, micronutrient supplementation, large-scale fortification of staple foods and condiments and point-of-use fortification through multiple micronutrient powders and fortified speciality foods. More recent data on micronutrient availability, intake and deficiency is urgently needed in Southeast Asia.

Benchmarking the nutrient composition and labelling practices of finger foods and snacks for older infants and young children across seven Southeast Asian countries.

Ensuring consumption of nutrient-dense, safe and appropriate complementary foods among older infants and young children (IYC) 6-36 months of age is critical for enabling optimal growth and development. The ubiquitous availability of and high demand for commercially packaged snack foods has culminated in a growing trend of snack food products specifically produced and promoted for older IYC. Commercially produced complementary foods (CPCF) that are finger foods/snacks often contain added sugars, excessive sodium content and high total sugar content, making them inappropriate for this young population. This study benchmarked the nutrient composition and labelling practices of CPCF finger foods/snacks available for purchase in seven countries in Southeast Asia. The study adapted a nutrient profiling model from the WHO Regional Office for Europe to determine the proportion of products suitable for promotion for older IYC. Of the total 606 products identified, 8.2% were automatically categorized as not suitable because they were confectionery items. Of the remaining 556 products assessed, over 85% failed to meet all nutrient composition requirements, with the presence of added sugars/sweeteners and excessive sodium and total sugar contents the primary reasons for failure. Products also demonstrated concerning labelling practices, with all of the products (98.6%) displaying an inappropriate claim on the label. These findings reveal major concerns with the nutrient composition and labelling practices of CPCF finger foods/snacks in the SEA region and should serve as an alarm bell for regulatory action. National binding legal measures, such as mandatory standards for composition and labelling are urgently needed.

Overpromoted and underregulated: National binding legal measures related to commercially produced complementary foods in seven Southeast Asian countries are not fully aligned with available guidance.

The market for commercially produced complementary foods (CPCF) is rapidly expanding in Southeast Asia; however, the existence and content of mandatory national policies, standards and legislation (binding legal measures) for CPCF in the region is unclear. To assess the status of national binding legal measures for CPCF in Southeast Asia, a legal and policy desk review was conducted in seven countries (Cambodia, Laos People's Democratic Republic, Indonesia, Malaysia, Philippines, Thailand and Viet Nam). The alignment of the national binding legal measures relevant to CPCF was assessed against guidance on CPCF nutrient composition and labelling requirements provided by Codex Alimentarius and the World Health Organization (WHO). Each of the seven countries had at least two national binding legal measures related to the nutrient composition or labelling of CPCF; however, there was limited alignment with the guidance from Codex and WHO. No country was fully aligned with the three CPCF-specific Codex standards/guidelines and only one country was in full alignment with the recommendations related to the protection of breastfeeding from the 'WHO Guidance on ending the inappropriate promotion of foods for infants and young children'. The findings of the review indicate that the existing national binding legal measures are insufficient to ensure that the CPCF sold as suitable for older infants and young children are nutritionally adequate and labelled in a responsible manner that does not mislead caregivers. Improved and enforced national binding legal measures for CPCF, in alignment with global guidance, are required to ensure that countries protect, promote and support optimal nutrition for children 6-36 months of age.

Targeted Molecular Profiling of Circulating Cell-Free DNA in Patients With Advanced Hepatocellular Carcinoma.

PURPOSE: Next-generation sequencing (NGS) of tumor-derived, circulating cell-free DNA (cfDNA) may aid in diagnosis, prognostication, and treatment of patients with hepatocellular carcinoma (HCC). The operating characteristics of cfDNA mutational profiling must be determined before routine clinical implementation. METHODS: This was a single-center, retrospective study with the primary objective of defining genomic alterations in circulating cfDNA along with plasma-tissue genotype agreement between NGS of matched tumor samples in patients with advanced HCC. cfDNA was analyzed using a clinically validated 129-gene NGS assay; matched tissue-based NGS was analyzed with a US Food and Drug Administration-authorized NGS tumor assay. RESULTS: Fifty-three plasma samples from 51 patients with histologically confirmed HCC underwent NGS-based cfDNA analysis. Genomic alterations were detected in 92.2% of patients, with the most commonly mutated genes including TERT promoter (57%), TP53 (47%), CTNNB1 (37%), ARID1A (18%), and TSC2 (14%). In total, 37 (73%) patients underwent paired tumor NGS, and concordance was high for mutations observed in patient-matched plasma samples: TERT (83%), TP53 (94%), CTNNB1 (92%), ARID1A (100%), and TSC2 (71%). In 10 (27%) of 37 tumor-plasma samples, alterations were detected by cfDNA analysis that were not detected in the patient-matched tumors. Potentially actionable mutations were identified in 37% of all cases including oncogenic/likely oncogenic alterations in TSC1/2 (18%), BRCA1/2 (8%), and PIK3CA (8%). Higher average variant allele fraction was associated with elevated alpha-fetoprotein, increased tumor volume, and no previous systemic therapy, but did not correlate with overall survival in treatment-naïve patients. CONCLUSION: Tumor mutation profiling of cfDNA in HCC represents an alternative to tissue-based genomic profiling, given the high degree of tumor-plasma NGS concordance; however, genotyping of both blood and tumor may be required to detect all clinically actionable genomic alterations.

Social cognition in cervical dystonia.

Background: Whilst traditionally considered a movement disorder, it is now generally accepted that cervical dystonia (CD) presents with additional non-motor symptoms which significantly impact quality of life. Our study primarily aimed to explore social cognition and levels of psychological distress in individuals with CD, in comparison to age- and sex-matched healthy controls. Methods: 20 participants with CD attending a specialist movement disorders clinic were recruited. 20 age and sex matched neurologically healthy controls were recruited in parallel. Participants completed the Hospital Anxiety and Depression Scale, and two novel social cognition tasks: The Cambridge Mindreading Face-Voice Battery (CAFMB) and the Edinburgh Social Cognition Test (ESCoT). Results: Participants with CD exhibited poorer complex emotion recognition abilities for visual and auditory stimuli, compared to controls on the CAFMB task. Participants with CD did not differ significantly from controls on performance on cognitive or affective Theory of Mind tasks, or interpersonal or intrapersonal understanding of social norms, as measured by the ESCoT. The proportion of depressive symptoms was significantly higher for participants with CD than controls. 40% of participants with CD reported clinically elevated depressive symptoms, and 60% reported clinically elevated anxiety. Poorer understanding of emotional facial expressions was associated with higher levels of depression in the CD group. Conclusions: Significant between-group differences between participants with CD and controls suggests socio-cognitive dysfunction is an important aspect of the non-motor syndrome of CD. Findings highlight the need for assessment of and intervention for both social cognitive difficulties and psychological distress in individuals with CD.