Exploring the Influence of Structured Familiarization to an Adjustable, Passive Load-Bearing Exoskeleton on Oxygen Consumption and Lower Limb Muscle Activation During Walking.

Walking patterns is modified during load carriage, resulting in an increased activation of lower limb muscles and energy expenditure. Negative effects of load carriage could be minimized by wearing an exoskeleton, but evidence on the effects are conflicting. The objectives of this study were to describe the influence of an adjustable, passive load-bearing exoskeleton on the metabolic cost of walking (MCW) and associated muscle activations, and to explore changes in MCW after a familiarization process. Thirteen participants walked on a treadmill with a 22.75 kg payload at six preselected speeds (from 0.67 to 1.56 m/s) under three walking conditions: 1) without exoskeleton (NoExo); 2) with exoskeleton before familiarization (ExoPre); and 3) with exoskeleton after familiarization (ExoPost). Metabolic data was normalized to walking speed to provide MCW. Multi-muscle surface electromyography (EMG) was time and amplitude normalized to the gait cycle to provide muscle activation patterns. The familiarization occurred over three weeks including exposure to the exoskeleton. Differences in MCW and muscle activations were compared using a nonparametric analysis of longitudinal data. There were statistically significant increases in MCW for all speeds in the ExoPre and ExoPost conditions compared the NoExo. The average muscle activation showed an increase during ExoPre and ExoPost for the three speeds evaluated. Post-hoc analysis showed no significant effect of the familiarization period on metabolic data. In conclusion, a first exposure to the adjustable exoskeleton increased MCW and muscle activations, but the familiarization process did not provide any benefits toward a reduction in MCW or reduction in muscle activations at all speeds evaluated.

Effect of statin use on liver enzymes and lipid profile in patients with Non-Alcoholic Fatty Liver Disease (NAFLD).

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease (CVD). Statins are recommended for treatment of dyslipidemia to reduce the overall cardiovascular risk in patients with NAFLD. However, statin treatment was underutilized and the effect of statins on liver enzymes remained unclear in this patient population. OBJECTIVES: This study aimed to provide real-world evidence of the safety and effect of statin use in patients with NAFLD. METHODS: We conducted a cross-sectional survey study of adults with NAFLD using pooled data from the US NHANES database 2009-2018. NAFLD was defined by Fatty Liver Index (FLI) ≥ 60 and United States Fatty Liver Index (USFLI) ≥ 30. Multivariate regression analyses adjusted for baseline clinical and demographic characteristics were performed to compare the liver enzymes and lipid profile between statin and non-statin users. RESULTS: The study included 2,533 adults with NAFLD, representing 22.6 million individuals in the US, with 27% receiving statin treatment between 2009 and 2018. The mean differences of liver enzymes for AST, ALT, ALP, and GGT between statin and non-statin users were -0.86 (p=0.539), -3.49 (p=0.042), -0.25 (p=0.913), and 0.57 (p=0.901), respectively. In individuals with NAFLD and dyslipidemia, total cholesterol and LDL levels were significantly lower in statin users compared to non-statin users (mean difference, -28.9; p<0.001 and -27.7; p<0.001). CONCLUSION: The use of statins was not associated with elevated liver enzymes in patients with NAFLD. Significantly lower levels of ALT, total cholesterol, and LDL were observed in statin users compared to non-statin users.

Clinical and pathological aspects of toxic myopathies.

As the most frequent cause of acquired myopathy, toxic myopathies are characterised by clinicopathological features that vary depending on the mode of action of the drugs or toxins involved. Although a large number of substances can induce myotoxicity, the main culprits are statins, alcohol, and corticosteroids. A rigorous, well-organised diagnostic approach is necessary to obtain a rapid diagnosis. For early diagnosis and management, it is important for clinicians to be aware that most toxic myopathies are potentially reversible, and the goal of treatment should be to avoid serious muscle damage.

Understanding maternal sepsis risk factors and bacterial etiology: A case control study protocol.

INTRODUCTION: Maternal disorders are the third leading cause of sepsis globally, accounting for 5.7 million (12%) cases in 2017. There are increasing concerns about the emergence of antimicrobial resistance (AMR) in bacteria commonly causing maternal sepsis. Our aim is to describe the protocol for a clinical and microbiology laboratory study to understand risk factors for and the bacterial etiology of maternal sepsis in a tertiary Obstetrics and Gynaecology Hospital. METHODS: This case-control study aims to recruit 100 cases and 200 controls at Tu Du Hospital in Ho Chi Minh City, Vietnam, which had approximately 55,000 births in 2022. Women aged ≥ 18 years and ≥ 28 weeks gestation having a singleton birth will be eligible for inclusion as cases or controls, unless they have an uncomplicated localised or chronic infection, or an infection with SARS-CoV-2. Cases will include pregnant or recently pregnant women with sepsis recognised between the onset of labour and/or time of delivery/cessation of pregnancy for up to 42 days post-partum. Sepsis will be defined as suspected or confirmed infection with an obstetrically modified Sequential Organ Failure Assessment score of ≥ 2, treatment with intravenous antimicrobials and requested cultures of any bodily fluid. Controls will be matched by age, location, parity, mode of delivery and gestational age. Primary and secondary outcomes are risk factors associated with the development of maternal sepsis, the frequency of adverse outcomes due to maternal sepsis, bacterial etiology and AMR profiles of cases and controls. DISCUSSION: This study will improve understanding of the epidemiology and clinical implications of maternal sepsis management including the presence of AMR in women giving birth in Vietnam. It will help us to determine whether women in this setting are receiving optimal care and to identify opportunities for improvement.

Boosting Urea-Assisted Natural Seawater Electrolysis in 3D Leaf-Like Metal-Organic Framework Nanosheet Arrays Using Metal Node Engineering.

Metal node engineering, which can optimize the electronic structure and modulate the composition of poor electrically conductive metal-organic frameworks, is of great interest for electrochemical natural seawater splitting. However, the mechanism underlying the influence of mixed-metal nodes on electrocatalytic activities is still ambiguous. Herein, a strategic design is comprehensively demonstrated in which mixed Ni and Co metal redox-active centers are uniformly distributed within NH2-Fe-MIL-101 to obtain a synergistic effect for the overall enhancement of electrocatalytic activities. Three-dimensional mixed metallic MOF nanosheet arrays, consisting of three different metal nodes, were in situ grown on Ni foam as a highly active and stable bifunctional catalyst for urea-assisted natural seawater splitting. A well-defined NH2-NiCoFe-MIL-101 reaches 1.5 A cm-2 at 360 mV for the oxygen evolution reaction (OER) and 0.6 A cm-2 at 295 mV for the hydrogen evolution reaction (HER) in freshwater, substantially higher than its bimetallic and monometallic counterparts. Moreover, the bifunctional NH2-NiCoFe-MIL-101 electrode exhibits eminent catalytic activity and stability in natural seawater-based electrolytes. Impressively, the two-electrode urea-assisted alkaline natural seawater electrolysis cell based on NH2-NiCoFe-MIL-101 needs only 1.56 mV to yield 100 mA cm-2, much lower than 1.78 V for alkaline natural seawater electrolysis cells and exhibits superior long-term stability at a current density of 80 mA cm-2 for 80 h.

Anti-Angiogenic Tyrosine Kinase Inhibitor-Related Toxicities Among Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Targeting of angiogenesis has become a major therapeutic approach for the treatment of various advanced cancers. There are many unresolved questions on the toxicity of anti-angiogenic tyrosine kinase inhibitors (TKIs). OBJECTIVE: We performed a meta-analysis to assess the toxicity prevalence of the different anti-angiogenic TKIs among cancer patients and in subpopulations of interest including patients with renal cell carcinoma. PATIENTS AND METHODS: We searched the MEDLINE and Cochrane Library databases to November 2023. Clinical trials were eligible if they set out to report the grade ≥3 toxicities related to one of the seven currently approved anti-angiogenic TKIs as monotherapies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was applied with PROSPERO (CRD42023411946). RESULTS: The 421 eligible studies included a total of 56,895 cancer patients treated with anti-angiogenic TKI monotherapy. Twenty-four different cancer types were identified, mainly renal cell carcinoma (41.9% of the patients). The anti-angiogenic TKI was sorafenib (34.5% of the patients), sunitinib (30.5%), regorafenib (10.7%), pazopanib (9.4%), cabozantinib (7.7%), axitinib (4.3%), and lenvatinib (2.9%). The pooled prevalence of grade 3 and 4 toxicities was 56.1% (95% confidence interval 53.5-58.6), with marked between-study heterogeneity (I2 = 96.8%). Toxicity profiles varied considerably depending on the type of TKI, the cancer type, and the specific patient characteristics. In particular, Asian patients and elderly people had higher prevalences of severe toxicities, with pazopanib being the best-tolerated drug. For patients treated with sunitinib, particularly those with metastatic RCC, there was no significant difference in terms of toxicity according to the regimen schedule. CONCLUSIONS: This meta-analysis highlights the toxicity profiles of anti-angiogenic TKI monotherapies, and thus enables high-level recommendations for the choice of anti-angiogenic TKIs on the basis of the patient's age, ethnicity, comorbidities, and comedications, for personalized treatment.

Implementing narrow banding imaging with dual focus magnification for histological prediction of small rectosigmoid polyps in Vietnamese setting.

Background and Aim: Small rectosigmoid colorectal polyps (<10 mm) are prevalent, with a low prevalence of advanced neoplastic lesions. The "diagnose-and-leave" strategy, employing narrow band imaging (NBI), is gaining popularity for its safety and cost-effectiveness by reducing polypectomy complications and minimizing histopathology expenses. This study assessed the diagnostic efficacy of NBI with dual focus (DF) magnification for real-time neoplastic prediction of rectosigmoid polyps and explored the feasibility of implementing this strategy in Vietnam. Methods: In a prospective single-center study, 307 rectosigmoid polyps from 245 patients were analyzed using three consecutive endoscopic modes: white light endoscopy (WLE), NBI, and NBI-DF. Endoscopists assessed polyps for size, location, macroscopic shape, optical diagnosis, and confidence levels before histopathological evaluation. High confidence was assigned when the polyp exhibited all features of a single histology type. Predictions were compared with final histopathology results. Results: Of the total, 237 (77.2%) were diminutive (≤5 mm) polyps, and 18 (5.8%) were advanced neoplastic lesions. WLE + NBI and WLE + NBI + NBI-DF exhibited significantly higher accuracy compared to WLE (88.6% and 90.2% vs 74.2%, P < 0.01). For diminutive polyps, the DF mode significantly increased the rate of high-confidence optical diagnoses (89.1% vs 94.9%, P < 0.001). WLE + NBI + NBI-DF demonstrated high sensitivity (90.1%), specificity (95.5%), and negative predictive value (93.4%) in high-confidence predictions, enabling the implementation of the "diagnose-and-leave" strategy. This approach would have reduced 58.2% of unnecessary polypectomies without missing any advanced neoplastic lesions. Conclusion: NBI and DF modes provide accurate neoplastic predictions for rectosigmoid polyps. For diminutive polyps, DF magnification improves the confidence level of the optical diagnosis, allowing the safe implementation of the "diagnose-and-leave" strategy.

Decellularised plant scaffolds facilitate porcine skeletal muscle tissue engineering for cultivated meat biomanufacturing.

Cultivated meat (CM) offers a sustainable and ethical alternative to conventional animal agriculture, involving cell maturation in a controlled environment. To emulate the structural complexity of traditional meat, the development of animal-free and edible scaffolds is crucial, providing vital physical and biological support during tissue development. The aligned vascular bundles of the decellularised asparagus scaffold were selected to facilitate the attachment and alignment of murine myoblasts (C2C12) and porcine adipose-derived mesenchymal stem cells (pADMSCs). Muscle differentiation was assessed through immunofluorescence staining with muscle markers, including Myosin heavy chain (MHC), Myogenin (MYOG), and Desmin. The metabolic activity of Creatine Kinase in C2C12 differentiated cells significantly increased compared to proliferated cells. Quantitative PCR analysis revealed a significant increase in Myosin Heavy Polypeptide 1 (MYH1) and MYOG expression compared to Day 0. These results highlight the application of decellularised plant scaffold (DPS) as a promising, edible material conducive to cell attachment, proliferation, and differentiation into muscle tissue. To create a CM prototype with biological mimicry, pADMSC-derived muscle and fat cells were also co-cultured on the same scaffold. The co-culture was confirmed through immunofluorescence staining of muscle markers and LipidTOX staining, revealing distinct muscle fibres and adipocytes containing lipid droplets respectively. Texture profile analysis conducted on uncooked CM prototypes and pork loin showed no significant differences in textural values. However, the pan-fried CM prototype differed significantly in hardness and chewiness compared to pork loin. Understanding the scaffolds' textural profile enhances our insight into the potential sensory attributes of CM products. DPS shows potential for advancing CM biomanufacturing.

Employing fruit juices to hydrolyze edible bird's nest and enhance the antioxidant, anti-tyrosinase, and wound-healing activities of the hydrolysates.

Enzymatic hydrolysis of edible bird's nest (EBN) has attracted great interest in both scientific and commercial fields due to the enhancement of solubility and nutraceutical values. The present study attempted to investigate the hydrolysis of EBN with papaya (Carica papaya L.), pineapple (Ananas comosus (L.) Merr.), and cantaloupe (Cucumis melo L.) juices as well as two commercial enzymes papain and bromelain. Our analysis revealed that EBN hydrolysis with pineapple juice and bromelain produced a degree of hydrolysis (DH) value of approximately 27 % while it was about 25 % for the hydrolysis with cantaloupe juice and 22 % for the hydrolysis with papaya juice and papain after 4 h of treatment. When EBN was digested by fruit juices and enzymes, the protein solubility and free sialic acid content were increased and the highest values were achieved for EBN hydrolysis with pineapple juice and bromelain (estimately 11 mg/mL of soluble protein and 18 g/kg of free sialic acid). The ABTS•+-scavenging, •OH-scavenging, and anti-tyrosinase capacities were higher in the EBN hydrolysates by papaya juice (IC50 of 0.034, 0.108, and 0.419 mg/mL, respectively), pineapple juice (IC50 of 0.025, 0.045, and 0.190 mg/mL, respectively), and cantaloupe juice (IC50 of 0.031 mg/mL, 0.056, and 0.339 mg/mL, respectively) than in the hydrolysates by unhydrolyzed EBN (IC50 of 0.094, 0.366, and 1.611 mg/mL, respectively). An improvement in ABTS•+-scavenging, •OH-scavenging, and anti-tyrosinase abilities was also observed for the hydrolysates by papain (IC50 of 0.041, 0.129, and 0.417 mg/mL, respectively) and bromelain (IC50 of 0.025, 0.069, and 0.336 mg/mL, respectively) but in a lesser extent as compared to the hydrolysates by respective papaya and pineapple juices. Noticeably, the EBN hydrolysates by fruit juices remarkably enhanced the wound closure in human fibroblasts by about 1.4-1.8 times after 24 h of treatment whereas this property was insignificant in the hydrolysates by enzymes. As papaya, pineapple, and cantaloupe juices are easily obtainable and have pleasant flavors, our results provide a possible method to hydrolyze EBN and apply the resultant hydrolysates in functional food products.

The prevalence of Pfk13 polymorphism in malaria patients treated with artemisinin-based therapy: a systematic review and meta-analysis.

Artemisinin (ART) combination therapy is the main treatment for malaria. Pfk13 mutations (or K13 mutations, Kelch 13) are associated with ART resistance. This study aims to conduct a systematic review and meta-analysis of the prevalence of K13 mutations with ART resistance in malaria-endemic countries. An electronic search of studies in 2018 and a manual search in 2020 were performed to identify relevant studies. The risk of bias was assessed using the National Institutes of Health (NIH) quality assessment tool for observational cohort and cross-sectional studies. Data analysis was performed using R 4.1.0. Heterogeneity was estimated using the statistic I2 and Cochran Q test. A total of 170 studies were included in our review. Of these, 55 studies investigated the prevalence of K13 mutations in Southeast Asia. The meta-analysis showed that Southeast Asia had the highest prevalence of K13 mutations, whereas Africa, South America, Oceania, and other Asian countries outside Southeast Asia had a low prevalence of K13 mutations. The C580Y mutation was the most common in Southeast Asia with 35.5% (95%CI: 25.4-46.4%), whereas the dominant mutation in Africa was K189T (22.8%, 95%CI: 7.6-43.2%). This study revealed the emergence of ART resistance associated with K13 mutations in Southeast Asia. The diversity of each type of K13 mutation in other regions was also reported.

The genetic landscape of chromosomal aberrations in 3776 Vietnamese fetuses with clinical anomalies during pregnancy.

Background: Copy number variation sequencing (CNV-seq) is a powerful tool to discover structural genomic variation, but limitations associated with its retrospective study design and inadequate diversity of participants can be impractical for clinical application. Aim: This study aims to use CNV-seq to assess chromosomal aberrations in pregnant Vietnamese women. Materials & methods: A large-scale study was conducted on 3776 pregnant Vietnamese women with abnormal ultrasound findings. Results: Chromosomal aberrations were found in 448 (11.86%) women. Of these, 274 (7.26%) had chromosomal aneuploidies and 174 (4.61%) carried pathogenic/likely pathogenic CNVs. Correlations were established between chromosomal aberrations and various phenotypic markers. Conclusion: This comprehensive clinical study illuminates the pivotal role of CNV-seq in prenatal diagnosis for pregnancies featuring fetal ultrasound anomalies.

[Box: see text].

Scoring PD-L1 Expression in Urothelial Carcinoma: An International Multi-Institutional Study on Comparison of Manual and Artificial Intelligence Measurement Model (AIM-PD-L1) Pathology Assessments.

Assessing programmed death ligand 1 (PD-L1) expression on tumor cells (TCs) using Food and Drug Administration-approved, validated immunoassays can guide the use of immune checkpoint inhibitor (ICI) therapy in cancer treatment. However, substantial interobserver variability has been reported using these immunoassays. Artificial intelligence (AI) has the potential to accurately measure biomarker expression in tissue samples, but its reliability and comparability to standard manual scoring remain to be evaluated. This multinational study sought to compare the %TC scoring of PD-L1 expression in advanced urothelial carcinoma, assessed by either an AI Measurement Model (AIM-PD-L1) or expert pathologists. The concordance among pathologists and between pathologists and AIM-PD-L1 was determined. The positivity rate of ≥ 1%TC PD-L1 was between 20-30% for 8/10 pathologists, and the degree of agreement and scoring distribution for among pathologists and between pathologists and AIM-PD-L1 was similar both scored as a continuous variable or using the pre-defined cutoff. Numerically higher score variation was observed with the 22C3 assay than with the 28-8 assay. A 2-h training module on the 28-8 assay did not significantly impact manual assessment. Cases exhibiting significantly higher variability in the assessment of PD-L1 expression (mean absolute deviation > 10) were found to have patterns of PD-L1 staining that were more challenging to interpret. An improved understanding of sources of manual scoring variability can be applied to PD-L1 expression analysis in the clinical setting. In the future, the application of AI algorithms could serve as a valuable reference guide for pathologists while scoring PD-L1.

Discovery and technical validation of high-performance methylated DNA markers for the detection of cervical lesions at risk of malignant progression in low- and middle-income countries.

BACKGROUND: Cervical cancer remains a leading cause of death, particularly in developing countries. WHO screening guidelines recommend human papilloma virus (HPV) detection as a means to identify women at risk of developing cervical cancer. While HPV testing identifies those at risk, it does not specifically distinguish individuals with neoplasia. We investigated whether a quantitative molecular test that measures methylated DNA markers could identify high-risk lesions in the cervix with accuracy. RESULTS: Marker discovery was performed in TCGA-CESC Infinium Methylation 450 K Array database and verified in three other public datasets. The panel was technically validated using Quantitative Multiplex-Methylation-Specific PCR in tissue sections (N = 252) and cervical smears (N = 244) from the USA, South Africa, and Vietnam. The gene panel consisted of FMN2, EDNRB, ZNF671, TBXT, and MOS. Cervical tissue samples from all three countries showed highly significant differential methylation in squamous cell carcinoma (SCC) with a sensitivity of 100% [95% CI 74.12-100.00], and specificity of 91% [95% CI 62.26-99.53] to 96% [95% CI 79.01-99.78], and receiver operating characteristic area under the curve (ROC AUC) = 1.000 [95% CI 1.00-1.00] compared to benign cervical tissue, and cervical intraepithelial neoplasia 2/3 with sensitivity of 55% [95% CI 37.77-70.84] to 89% [95% CI 67.20-98.03], specificity of 93% [95% CI 84.07-97.38] to 96% [95% CI 79.01-99.78], and a ROC AUC ranging from 0.793 [95% CI 0.68-0.89] to 0.99 [95% CI 0.97-1.00] compared to CIN1. In cervical smears, the marker panel detected SCC with a sensitivity of 87% [95% CI 77.45-92.69], specificity 95% [95% CI 88.64-98.18], and ROC AUC = 0.925 [95% CI 0.878-0.974] compared to normal, and high-grade squamous intraepithelial lesion (HSIL) at a sensitivity of 70% (95% CI 58.11-80.44), specificity of 94% (95% CI 88.30-97.40), and ROC AUC = 0.884 (95% CI 0.822-0.945) compared to low-grade intraepithelial lesion (LSIL)/normal in an analysis of pooled data from the three countries. Similar to HPV-positive, HPV-negative cervical carcinomas were frequently hypermethylated for these markers. CONCLUSIONS: This 5-marker panel detected SCC and HSIL in cervical smears with a high level of sensitivity and specificity. Molecular tests with the ability to rapidly detect high-risk HSIL will lead to timely treatment for those in need and prevent unnecessary procedures in women with low-risk lesions throughout the world. Validation of these markers in prospectively collected cervical smear cells followed by the development of a hypermethylated marker-based cervical cancer detection test is warranted.

Knockout of formyl peptide receptor 1 reduces osteogenesis and bone healing.

AIMS: Formyl peptide receptor 1 (FPR1), from a G-protein coupled receptor family, was previously well-characterized in immune cells. But the function of FPR1 in osteogenesis and fracture healing was rarely reported. This study, using the FPR1 knockout (KO) mouse, is one of the first studies that try to investigate FPR1 function to osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in vitro and bone fracture healing in vivo. MATERIALS AND METHODS: Primary BMSCs were isolated from both FPR1 KO and wild type (WT) mice. Cloned mouse BMSCs (D1 cells) were used to examine role of FoxO1 in FPR1 regulation of osteogenesis. A closed, transverse fracture at the femoral midshaft was created to compare bone healing between KO and WT mice. Biomechanical and structural properties of femur were compared between healthy WT and KO mice. KEY FINDINGS: FPR1 expression increased significantly during osteogenesis of both primary and cloned BMSCs. Compared to BMSCs from FPR1 KO mice, WT BMSCs displayed considerably higher levels of osteogenic markers as well as mineralization. Osteogenesis by D1 cells was inhibited by either an FPR1 antagonist cFLFLF or a specific inhibitor of FoxO1, AS1842856. In addition, the femur from WT mice had better biomechanical properties than FPR1 KO mice. Furthermore, bone healing in WT mice was remarkably improved compared to FPR1 KO mice analyzed by X-ray and micro-CT. SIGNIFICANCE: These findings indicated that FPR1 played a vital role in osteogenic differentiation and regenerative capacity of fractured bone, probably through the activation of FoxO1 related signaling pathways.

A randomized double-blinded trial to assess recurrence of systemic allergic reactions following COVID-19 mRNA vaccination.

BACKGROUND: Systemic allergic reactions (sARs) following coronavirus disease 2019 (COVID-19) mRNA vaccines were initially reported at a higher rate than after traditional vaccines. OBJECTIVE: We aimed to evaluate the safety of revaccination in these individuals and to interrogate mechanisms underlying these reactions. METHODS: In this randomized, double-blinded, phase 2 trial, participants aged 16 to 69 years who previously reported a convincing sAR to their first dose of COVID-19 mRNA vaccine were randomly assigned to receive a second dose of BNT162b2 (Comirnaty) vaccine and placebo on consecutive days in a blinded, 1:1 crossover fashion at the National Institutes of Health. An open-label BNT162b2 booster was offered 5 months later if the second dose did not result in severe sAR. None of the participants received the mRNA-1273 (Spikevax) vaccine during the study. The primary end point was recurrence of sAR following second dose and booster vaccination; exploratory end points included biomarker measurements. RESULTS: Of 111 screened participants, 18 were randomly assigned to receive study interventions. Eight received BNT162b2 second dose followed by placebo; 8 received placebo followed by BNT162b2 second dose; 2 withdrew before receiving any study intervention. All 16 participants received the booster dose. Following second dose and booster vaccination, sARs recurred in 2 participants (12.5%; 95% CI, 1.6 to 38.3). No sAR occurred after placebo. An anaphylaxis mimic, immunization stress-related response (ISRR), occurred more commonly than sARs following both vaccine and placebo and was associated with higher predose anxiety scores, paresthesias, and distinct vital sign and biomarker changes. CONCLUSIONS: Our findings support revaccination of individuals who report sARs to COVID-19 mRNA vaccines. Distinct clinical and laboratory features may distinguish sARs from ISRRs.

Epidemiology of perioperative anaphylaxis in France in 2017-2018: the 11th GERAP survey.

BACKGROUND: Perioperative anaphylaxis is rare but is associated with significant morbidity. This complication has been well described in France by the GERAP (Groupe d'Etude des Réactions Anaphylactiques Périopératoires), a network focused on its study. The epidemiology of perioperative anaphylaxis is evolving, influenced by environmental factors and clinical practice. The aim of this study was to update the epidemiology of perioperative anaphylaxis in France. METHODS: This multicentre retrospective study was performed in 26 allergy clinics of the GERAP network in 2017-8. RESULTS: There were 765 patients with perioperative anaphylaxis included. Most cases were severe, with 428 (56%) reactions graded as 3 or 4 according to the Ring and Messmer classification. Skin test results were available for 676 patients, with a culprit agent identified in 471 cases (70%). Neuromuscular blocking agents were the main cause of perioperative anaphylaxis (n=281; 60%), followed by antibiotics (n=118; 25%) and patent blue dye (n=11; 2%). Cefazolin was the main antibiotic responsible for perioperative anaphylaxis (52% of antibiotic-related reactions). Suxamethonium and rocuronium were the main neuromuscular blocking agents responsible for perioperative anaphylaxis with 7.1 (6.1-8.4) and 5.6 (4.2-7.4) reactions per 100,000 vials sold, respectively, whereas cefazolin-related cases were estimated at 0.7 (0.5-0.9) reactions per 100,000 vials sold. CONCLUSIONS: Our results confirm that most commonly identified triggering agents remain neuromuscular blocking agents. Reactions to antibiotics, particularly cefazolin, are becoming increasingly frequent. The origin of sensitisation to cefazolin is unknown, as no cross-sensitisation has been described, and it should be the subject of further study. Perioperative anaphylaxis should be followed over the years and understood given the changing triggers. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04654923).

Spontaneous Coronary Artery Dissection and Fibromuscular Dysplasia: A Case Series and Genetic Links.

Spontaneous coronary artery dissection (SCAD) is a rare cause of myocardial infarction in young women. An association of fibromuscular dysplasia (FMD) with SCAD has been well established; a significant proportion of SCAD patients may have typical FMD findings in other noncoronary arteries. The current consensus recommends arterial imaging screening from head to pelvis using computed tomography angiography (CTA) or magnetic resonance angiography (MRA) in SCAD. Genetic testing for FMD should be considered in high-risk cases. We present two cases of SCAD associated with FMD and discuss the significance of genetic screening in such patients.

Rifampicin resistant Mycobacterium tuberculosis in Vietnam, 2020-2022.

Objective: We conducted a descriptive analysis of multi-drug resistant tuberculosis (MDR-TB) in Vietnam's two largest cities, Hanoi and Ho Chi Minh city. Methods: All patients with rifampicin resistant tuberculosis were recruited from Hanoi and surrounding provinces between 2020 and 2022. Additional patients were recruited from Ho Chi Minh city over the same time period. Demographic data were recorded from all patients, and samples collected, cultured, whole genome sequenced and analysed for drug resistance mutations. Genomic susceptibility predictions were made on the basis of the World Health Organization's catalogue of mutations in Mycobacterium tuberculosis associated with drug resistance, version 2. Comparisons were made against phenotypic drug susceptibility test results where these were available. Multivariable logistic regression was used to assess risk factors for previous episodes of tuberculosis. Results: 233/265 sequenced isolates were of sufficient quality for analysis, 146 (63 %) from Ho Chi Minh City and 87 (37 %) from Hanoi. 198 (85 %) were lineage 2, 20 (9 %) were lineage 4, and 15 (6 %) were lineage 1. 17/211 (8 %) for whom HIV status was known were infected, and 109/214 (51 %) patients had had a previous episode of tuberculosis. The main risk factor for a previous episode was HIV infection (odds ratio 5.1 (95 % confidence interval 1.3-20.0); p = 0.021). Sensitivity for predicting first-line drug resistance from whole genome sequencing data was over 90 %, with the exception of pyrazinamide (85 %). For moxifloxacin and amikacin it was 50 % or less. Among rifampicin-resistant isolates, prevalence of resistance to each non-first-line drug was < 20 %. Conclusions: Drug resistance among most MDR-TB strains in Vietnam's two largest cities is confined largely to first-line drugs. Living with HIV is the main risk factor among patients with MDR-TB for having had a previous episode of tuberculosis.

Generation of glioblastoma in mice engrafted with human cytomegalovirus-infected astrocytes.

Mounting evidence is identifying human cytomegalovirus (HCMV) as a potential oncogenic virus. HCMV has been detected in glioblastoma multiforme (GB). Herewith, we present the first experimental evidence for the generation of CMV-Elicited Glioblastoma Cells (CEGBCs) possessing glioblastoma-like traits that lead to the formation of glioblastoma in orthotopically xenografted mice. In addition to the already reported oncogenic HCMV-DB strain, we isolated three HCMV clinical strains from GB tissues that transformed HAs toward CEGBCs and generated spheroids from CEGBCs that resulted in the appearance of glioblastoma-like tumors in xenografted mice. These tumors were nestin-positive mostly in the invasive part surrounded by GFAP-positive reactive astrocytes. The glioblastoma immunohistochemistry phenotype was confirmed by EGFR and cMet gene amplification in the tumor parallel to the detection of HCMV IE and UL69 genes and proteins. Our results fit with an HCMV-induced glioblastoma model of oncogenesis in vivo which will open the door to new therapeutic approaches and assess the anti-HCMV treatment as well as immunotherapy in fighting GB which is characterized by poor prognosis.

Effectiveness of Dual-Focus Magnification on Confidence Levels in Optical Diagnosis of Small Colorectal Polyps.

Background and objectives Achieving accurate real-time optical diagnoses of colorectal polyps with high-confidence predictions is crucial for appropriate decision-making in daily practice. The dual-focus (DF) magnification mode helps endoscopists scrutinize subtle features of polyp surfaces and vessel patterns. This prospective study aimed to evaluate the impact of DF imaging on enhancing the rate of high-confidence narrow-band imaging (NBI)-based optical diagnosis. Methods Consecutive adult patients who underwent colonoscopy and had small colorectal polyps (<10 mm) were enrolled between September 2022 and May 2023. The optical diagnosis of each polyp was evaluated during colonoscopy in two stages by the same endoscopist, utilizing NBI with DF magnification (NDB-DF). A confidence level was assigned to each prediction. High confidence was indicated by clinical judgment when a polyp exhibited distinctive features associated solely with one histological subtype and lacked characteristics of any other subtype. All procedures were carried out with a prototype 190 series Exera III NBI system (Olympus Corporation, Tokyo, Japan) with DF magnification. Results The study included 413 patients with 623 polyps, comprising 483 ≤ 5 mm and 140 measuring 6-9 mm. The majority were low-grade adenomas (343 lesions), with 17 identified as high-grade adenomas, and none characterized as deep submucosal invasive carcinomas. NBI-DF significantly improved the rate of high-confidence optical diagnoses compared to NBI for both ≤ 5 mm polyps (93.1% vs. 87.5%, p < 0.0001) and 6-9 mm polyps (97.9% vs. 94.2%, p = 0.03). Furthermore, DF significantly facilitated the assessment of microvessel and surface pattern criteria (p < 0.01). Conclusion DF magnification markedly enhanced the rate of high-confidence NBI-based optical predictions for small colorectal polyps. This technique demonstrates the potential for improving the diagnostic yield in real-time optical diagnosis of colorectal polyps in the Vietnamese setting.