Multi-center evaluation of the Research Use Only NeuMoDx monkeypox virus (MPXV) fully automated real-time PCR assay.

The mpox outbreak, caused by monkeypox virus (MPXV), accelerated the development of molecular diagnostics. In this study, we detail the evaluation of the Research Use Only (RUO) NeuMoDx MPXV assay by multiple European and US sites. The assay was designed and developed by Qiagen for the NeuMoDx Molecular Systems. Primers and probes were tested for specificity and inclusivity in silico. The analytical sensitivity of the assay was determined by testing dilutions of synthetic and genomic MPXV DNA. A total of 296 clinical samples were tested by three sites; the Johns Hopkins University (US), UZ Gent (Belgium, Europe), and Hospital Universitario San Cecilio (Spain, Europe). The analytical sensitivity of the assay was 50 copies/mL for both clades I and II. The assay showed 100% in silico identity for 80 clade I and 99.98% in silico identity for 5,162 clade II genomes. Clade II primers and probes showed 100% in silico specificity; however, identity of at least one of the two sets of clade I primers and probes with variola, cowpox, camelpox, and vaccinia viruses was noticed. The clinical validation showed sensitivity of 99.21% [95% confidence interval (CI): 95.66-99.98%] and specificity of 96.64% (95% CI: 91.62-99.08%) for lesion swab samples. The NeuMoDx MPXV Test shows acceptable analytical and clinical performance. The assay improves the laboratory's workflow as it consolidates nucleic acid extraction, PCR, data analysis, and interpretation and can be interfaced. The Test Strip can differentiate clades I and II, which has important laboratory safety implications. IMPORTANCE: In this manuscript, we provide detailed in silico analysis and clinical evaluation of the assay using a large cohort of clinical samples across three academic centers in Europe and the United States. Because the assay differentiates MPXV clades I and II, this manuscript is timely due to the current need to rule out the regulated clade I by diagnostic clinical laboratories. In December 2023, and due to first report of cases of sexually transmitted clade I infections in the Democratic Republic of the Congo, when generic assays that do not differentiate the clades are used, samples are considered regulated. The assay meets the need of full automation and has a marked positive impact on the laboratory workflow.

Prediction of post-hepatectomy liver failure by preoperative gadoxetate disodium-enhanced magnetic resonance imaging.

BACKGROUND: Approximately 15% of patients experience post-hepatectomy liver failure after major hepatectomy. Poor hepatocyte uptake of gadoxetate disodium, a magnetic resonance imaging contrast agent, may be a predictor of post-hepatectomy liver failure. METHODS: A retrospective cohort study of patients undergoing major hepatectomy (≥3 segments) with a preoperative gadoxetate disodium-enhanced magnetic resonance imaging was conducted. The liver signal intensity (standardized to the spleen) and the functional liver remnant was calculated to determine if this can predict post-hepatectomy liver failure after major hepatectomy. RESULTS: In 134 patients, low signal intensity of the remnant liver standardized by signal intensity of the spleen in post-contrast images was associated with post-hepatectomy liver failure in multiple logistic regression analysis (Odds Ratio 0.112; 95% CI 0.023-0.551). In a subgroup of 33 patients with lower quartile of functional liver remnant, area under the curve analysis demonstrated a diagnostic accuracy of functional liver remnant to predict post-hepatectomy liver failure of 0.857 with a cut-off value for functional liver remnant of 1.4985 with 80.0% sensitivity and 89.3% specificity. CONCLUSION: Functional liver remnant determined by gadoxetate disodium-enhanced magnetic resonance imaging is a predictor of post-hepatectomy liver failure which may help identify patients for resection, reducing morbidity and mortality.

When is a Ghost Really Gone? A Systematic Review and Meta-analysis of the Accuracy of Imaging Modalities to Predict Complete Pathological Response of Colorectal Cancer Liver Metastases After Chemotherapy.

BACKGROUND: Administration of chemotherapy to patients with colorectal liver metastases may result in disappearing liver metastases (DLM). This poses a therapeutic dilemma due to the uncertainty of true complete (pathological) response. OBJECTIVE: We aimed to examine the diagnostic performance of imaging modalities in detecting true complete response in patients with DLM after chemotherapy. METHODS: We performed a systematic search for articles assessing the diagnostic performance of imaging modalities in evaluating DLM following chemotherapy. True complete response was defined as 1-year recurrence-free survival in non-resected patients or complete pathological response on histologic examination in resected patients. We calculated the negative predictive value (NPV) for detecting true complete response of each imaging modality using a random effects model. RESULTS: Thirteen studies comprising 332 patients with at least one DLM were included. The number of DLMs after chemotherapy was 955 with computed tomography (CT), 104 with positron emission tomography (PET), 50 with intraoperative ultrasound (IOUS), 585 with magnetic resonance imaging (MRI), and 175 with contrast-enhanced IOUS (CEIOUS). Substantial variation in study design, patient characteristics, and imaging features was observed. Pooled NPV was 0.79 (95% confidence interval [CI] 0.53-0.96), 0.73 (95% CI 0.58-0.85), 0.54 (95% CI 0.37-0.7), 0.47 (95% CI 0.34-0.61), and 0.22 (95% CI 0.11-0.39) for CEIOUS, MRI, IOUS, CT, and PET, respectively. CONCLUSION: After chemotherapy, MRI or CEIOUS are the most accurate imaging modalities for assessment of DLM and should be used routinely in this context. Given the high NPV of these two modalities, surgical resection of visible CRLM is warranted if technically possible, even if DLM remain.

Mitotic Intragenic Recombination: A Mechanism of Survival for Several Congenital Disorders of Glycosylation.

Congenital disorders of glycosylation (CDGs) are disorders of abnormal protein glycosylation that affect multiple organ systems. Because most CDGs have been described in only a few individuals, our understanding of the associated phenotypes and the mechanisms of individual survival are limited. In the process of studying two siblings, aged 6 and 11 years, with MOGS-CDG and biallelic MOGS (mannosyl-oligosaccharide glucosidase) mutations (GenBank: NM_006302.2; c.[65C>A; 329G>A] p.[Ala22Glu; Arg110His]; c.[370C>T] p.[Gln124(∗)]), we noted that their survival was much longer than the previous report of MOGS-CDG, in a child who died at 74 days of age. Upon mutation analysis, we detected multiple MOGS genotypes including wild-type alleles in their cultured fibroblast and peripheral blood DNA. Further analysis of DNA from cultured fibroblasts of six individuals with compound heterozygous mutations of PMM2 (PMM2-CDG), MPI (MPI-CDG), ALG3 (ALG3-CDG), ALG12 (ALG12-CDG), DPAGT1 (DPAGT1-CDG), and ALG1 (ALG1-CDG) also identified multiple genotypes including wild-type alleles for each. Droplet digital PCR showed a ratio of nearly 1:1 wild-type to mutant alleles for most, but not all, mutations. This suggests that mitotic recombination contributes to the survival and the variable expressivity of individuals with compound heterozygous CDGs. This also provides an explanation for prior observations of a reduced frequency of homozygous mutations and might contribute to increased levels of residual enzyme activity in cultured fibroblasts of individuals with MPI- and PMM2-CDGs.

Delayed tumour enhancement on gadoxetate-enhanced MRI is associated with overall survival in patients with colorectal liver metastases.

OBJECTIVES: To determine whether tumour enhancement on preoperative delayed-phase gadoxetate-enhanced MRI can predict long-term survival in patients with colorectal liver metastases (CRCLM) post-hepatectomy. MATERIALS AND METHODS: Sixty-five patients who received a preoperative gadoxetate-enhanced MRI prior to liver resection for CRCLM from January 1, 2010, to December 31, 2012, were included in this retrospective study. Target tumour enhancement (TuEn) was calculated as the mean percentage increase in SNR from precontrast to 10-min or 20-min delayed phase for up to two target lesions. Per-patient TuEn was stratified into weak and strong enhancement based on the cut-off determined by the Youden Index for 3-year survival. Kaplan-Meier and Cox regression analyses were used to determine whether tumour enhancement could predict overall survival independent of potential confounders (clinical risk score). RESULTS: The proportion surviving at 3 years was 85.1% in patients with strong TuEn at 10 min vs. 56.5% in those with weak TuEn at 10 min (p = 0.001). The proportion surviving at 3 years was 79.4% in patients with strong TuEn at 20 min vs. 58.7% in those with weak TuEn at 20 min (p = 0.011). After adjusting for potential confounders, the hazard ratio of death was 0.24 (p = 0.009) in patients who had weak TuEn at 10 min and 0.32 (p = 0.018) in patients who had weak TuEn at 20 min. CONCLUSIONS: Strong delayed tumour enhancement seen on gadoxetate-enhanced MRI is associated with overall survival in patients with CRCLM post-hepatectomy and may be useful for preoperative risk stratification. KEY POINTS: • Delayed tumour enhancement of colorectal liver metastases on gadoxetate-enhanced MRI is associated with survival post-hepatectomy • Delayed tumour enhancement of colorectal liver metastases on gadoxetate-enhanced MRI can be measured at both 10 min and 20 min post-contrast injection.

Late gadolinium MRI enhancement of colorectal liver metastases is associated with overall survival among nonsurgical patients.

PURPOSE: To determine if late gadolinium MRI enhancement of colorectal liver metastases (CRCLM) is associated with overall survival among nonsurgical patients. MATERIALS AND METHODS: This retrospective study was approved by the institutional research ethics board. Late gadolinium enhancement was measured using target tumour enhancement (TTE) in all nonsurgical patients with CRCLM who received a 10-min delayed phase gadobutrol-enhanced liver MRI between March 1, 2006, and August 31, 2014. A total of 122 patients met inclusion/exclusion criteria. Patients were dichotomized into strong and weak TTE. Kaplan-Meier and Cox regression statistics were used to determine whether TTE was associated with overall survival. Noncontributory potential confounding variables (age, sex, number and size of metastases, carcinoembryonic (CEA) level, and presence of extrahepatic disease) were excluded from the final Cox regression model using the backward Wald elimination. Subgroup Kaplan-Meier survival analyses were performed on patients who were chemotherapy-naïve and chemotherapy-treated at the time of MRI. RESULTS: Strong TTE had increased survival compared with those with weak TTE on Kaplan-Meier analysis (2-year survival: 69.8% vs. 43.5%, p = 0.002). Among 96 patients where data was available for multivariable analysis, weak TTE was associated with death (adjusted hazard ratio 0.25, 95% CI 0.11-0.59, p = 0.002), after adjusting for CEA level. Other potential confounders were noncontributory. Subgroup analyses demonstrated that strong TTE had increased survival compared with those with weak TTE in both the chemotherapy-naïve (p = 0.047) and chemotherapy-treated (p = 0.008) groups. CONCLUSION: Strong late gadolinium MRI enhancement of CRCLM is associated with overall survival among nonsurgical patients. KEY POINTS: • MRI enhancement of colorectal liver metastases is associated with overall survival in nonsurgical patients. • MRI enhancement of colorectal liver metastases is associated with overall survival in both chemotherapy-naïve and chemotherapy-treated subgroups.

Late Gadolinium Hyperintensity of Suspected Colorectal Liver Metastases on Gadofosveset-Enhanced Magnetic Resonance Imaging: A Predictor of Benignity and a Potential Problem-Solving Tool.

PURPOSE: Late gadolinium hyperintensity (LGH) is sometimes seen in colorectal liver metastasis (CRLM) and represents a significant diagnostic pitfall due to overlap with LGH in benign hemangiomas; therefore, the objective of this study was to determine the prevalence of LGH and the ability of LGH to differentiate between CRLM and benign lesions with intravascular (gadofosveset) vs extracellular contrast agents (gadobutrol). METHODS: Patients with known colorectal cancer and suspected liver lesions were prospectively recruited into this institutional review board-approved, single institution study and received magnetic resonance imaging of the liver with gadofosveset and gadobutrol. The prevalence of LGH for CRLMs and solid benign lesions was determined. Receiver operating characteristics curves were determined for the presence of LGH as a predictor of benignity. The utility of LGH to differentiate between CRLM and solid benign lesions using gadofosveset vs gadobutrol was compared using the generalized estimating equation. RESULTS: Twenty-five patients with 131 solid focal liver lesions were recruited. The prevalence of LGH of CRLMs was 11.2% (95% confidence interval [CI]: 0.5%-21.8%) with gadofosveset vs 63.7% (95% CI: 45.7%-81.7%) with gadobutrol. The area under the receiver operating characteristic curve for the presence of LGH as a predictor of benignity was 0.86 using gadofosveset vs 0.75 using gadobutrol. Both LGH (P = .003) and the interaction of contrast agent and LGH (P = .003) statistically significantly differentiated CRLM from benign lesions. CONCLUSION: LGH is more common with extracellular than with intravascular contrast agents and is statistically significantly associated with benign lesions rather than metastases.

Late gadolinium enhancement of colorectal liver metastases post-chemotherapy is associated with tumour fibrosis and overall survival post-hepatectomy.

PURPOSE: To determine whether late gadolinium MRI enhancement of colorectal liver metastases (CRCLM) post-chemotherapy is associated with tumour fibrosis and survival post-hepatectomy. MATERIALS AND METHODS: The institutional review board approved this retrospective cohort study and waived the requirement for informed consent. A cohort of 121 surgical patients who received preoperative MRI after chemotherapy between 2006-2012 was included in this study. Target tumour enhancement (TTE), defined as the mean contrast-to-noise ratio of up to two target lesions on late-phase gadobutrol-enhanced MRI, was determined by two independent raters. The average TTE was correlated with tumour fibrosis on post-hepatectomy specimens using Spearman correlation and with survival post-hepatectomy using Kaplan-Meier and Cox regression. Inter-rater reliability was determined using relative intra-class correlation coefficients. RESULTS: In the surgical cohort (mean age: 63.0 years; male: 58%), TTE was associated with tumour fibrosis (r = 0.43, p < 0.001). Strong TTE was associated with improved survival compared to weak TTE (3-year survival: 88.4% vs. 58.8%, p = 0.003) with a hazard ratio of 0.32 (95% CI: 0.14-0.75, p = 0.008), after taking into account known prognostic variables. Inter-rater reliability was very good with a relative intraclass correlation of 0.84 (95% CI: 0.77-0.89). CONCLUSION: Late gadolinium MRI enhancement of CRCLM post-chemotherapy is associated with tumour fibrosis and survival. KEY POINTS: • MRI enhancement of colorectal liver metastases is associated with survival post-hepatectomy • MRI enhancement of chemotherapy-treated colorectal liver metastases correlates with tumour fibrosis • Measuring late MRI enhancement using target tumour enhancement is reliable.

Coffin-Siris syndrome: phenotypic evolution of a novel SMARCA4 mutation.

Coffin-Siris Syndrome (CSS) is an intellectual disability disorder caused by mutation of components of the SWI/SNF chromatin-remodeling complex. We describe the evolution of the phenotypic features for a male patient with CSS from birth to age 7 years and 9 months and by review of reported CSS patients, we expand the phenotype to include neonatal and infantile hypertonia and upper airway obstruction. The propositus had a novel de novo heterozygous missense mutation in exon 17 of SMARCA4 (NM_001128849.1:c.2434C>T (NP_001122321.1:p.Leu812Phe)). This is the first reported mutation within motif Ia of the SMARCA4 SNF2 domain. In summary, SMARCA4-associated CSS is a pleiotropic disorder in which the pathognomic clinical features evolve and for which the few reported individuals do not demonstrate a clear genotype-phenotype correlation.

Diagnostic test accuracy of preoperative nutritional screening tools in adults for malnutrition: a systematic review and network meta-analysis.

BACKGROUND: Good nutritional screening tests can triage malnourished patients for further assessment and management by dietitians before surgery to reduce the risk of postoperative complications. The authors assessed the diagnostic test accuracy of common nutritional screening tools for preoperative malnutrition in adults undergoing surgery and determined which test had the highest accuracy. METHODS: MEDLINE, EMBASE, CINAHL, and Web of Science were searched for relevant titles with no language restriction from inception till 1 January 2023. Studies reporting on the diagnostic test accuracy of preoperative malnutrition in adults using one or more of the following index nutritional screening tools were included: Malnutrition Screening Tool (MST), Malnutrition Universal Screening Tool (MUST), Mini Nutritional Assessment (MNA), short-form Mini Nutritional Assessment (MNA-SF), Nutritional Risk Index (NRI), Nutrition Risk Screening Tool 2002 (NRS-2002), and Preoperative Nutrition Screening (PONS). The reference standard was the Subjective Global Assessment (SGA) before surgery. Random-effects bivariate binomial model meta-analyses, meta-regressions, and a network meta-analysis were used to estimate the pooled and relative sensitivities and specificities. RESULTS: Of the 16 included studies (5695 participants with an 11 957 index and 11 957 SGA tests), all were conducted after hospital admission before surgery. Eleven studies ( n =3896) were at high risk of bias using the Quality Assessment of Diagnostic Accuracy Studies tool due to a lack of blinded assessments. MUST had the highest overall test accuracy performance (sensitivity 86%, 95% CI: 75-93%; specificity 89%, 95% CI: 83-93%). Network meta-analysis showed NRI had similar relative sensitivity (0.93, 95% CI: 0.77-1.13) but lower relative specificity (0.75, 95% CI: 0.61-0.92) than MUST. CONCLUSIONS: Of all easy-to-use tests applicable at the bedside, MUST had the highest test accuracy performance for screening preoperative malnutrition. However, its predictive accuracy is likely insufficient to justify the application of nutritional optimization interventions without additional assessments.

Clinical performance evaluation of the Aptima viral assays for the quantitation of HIV-1, HCV, and HBV in plasma samples.

The clinical performance of the Aptima® HIV-1 Quant Dx, Aptima HCV Quant Dx, and Aptima HBV Quant Dx were evaluated and compared to the Roche cobas HIV-1, HCV, and HBV assays performed on the Roche cobas 6800 system. The Aptima Quant assays exhibited an overall percent agreement of 99.4% for HBV, 98.3% for HCV, and 85.14% for HIV-1. The average log difference between the Aptima and Roche assays was below 0.2 IU (or copies)/mL and the quantitative correlation's (R-squared value (R2)) was between 0.95 and 0.97. The Aptima viral assays demonstrated a high level of quantitative correlation with the Roche cobas assays for HCV, HBV, and HIV-1.

A radiomic biomarker for prognosis of resected colorectal cancer liver metastases generalizes across MRI contrast agents.

Introduction: Contrast-enhanced MRI is routinely performed as part of preoperative work-up for patients with Colorectal Cancer Liver Metastases (CRLM). Radiomic biomarkers depicting the characteristics of CRLMs in MRI have been associated with overall survival (OS) of patients, but the reproducibility and clinical applicability of these biomarkers are limited due to the variations in MRI protocols between hospitals. Methods: In this work, we propose a generalizable radiomic model for predicting OS of CRLM patients who received preoperative chemotherapy and delayed-phase contrast enhanced (DPCE) MRIs prior to hepatic resection. This retrospective two-center study included three DPCE MRI cohorts (n=221) collected between January 2006 and December 2012. A 10-minute delayed Gd-DO3A-butrol enhanced MRI discovery cohort was used to select features based on robustness across contrast agents, correlation with OS and pairwise Pearson correlation, and to train a logistic regression model that predicts 3-year OS. Results: The model was evaluated on a 10-minute delayed Gd-DO3A-butrol enhanced MRI validation cohort (n=121), a 20-minute delayed Gd-EOB-DTPA (n=72) cohort from the same institute, and a 5-minute delayed Gd-DTPA cohort (n=28) from an independent institute. Two features were selected: minor axis length and dependence variance. The radiomic signature model stratified high-risk and low-risk CRLM groups in the Gd-DO3Abutrol (HR = 6.29, p = .007), Gd-EOB-DTPA (HR = 3.54, p = .003) and Gd-DTPA (HR = 3.16, p = .04) validation cohorts. Discussion: While most existing MRI findings focus on a specific contrast agent, our study shows the potential of MRI features to be generalizable across main-stream contrast agents at delayed phase.

Comparison of instructor-led compression-only cardiopulmonary resuscitation and automated external defibrillator training for secondary school students: A multicenter noninferiority randomized trial.

Background: Many barriers exist to the wider and sustainable implementation of basic life support (BLS) training in secondary schools. Whether trained teacher instructors are not worse than healthcare instructors by 20% (noninferiority margin) of simulated BLS skills for secondary school students is unclear. Methods: We conducted a two-armed, parallel, noninferiority, blinded, randomized controlled trial at four secondary schools in Hong Kong after teachers had undergone BLS training. Students were randomized to either the trained teacher or healthcare instructor group for the 2-hour compression-only cardiopulmonary resuscitation and automated external defibrillator (CO-CPRAED) course. The assessors for the students' BLS skill performance six months after the CO-CPRAED course were blinded. Results: Of the 33 trained teachers, 13 (39.4%) volunteered to be instructors for the CO-CPRAED course. Three hundred and eleven students (median age: 15 years, 67% males) were randomized to either the teacher (n = 161) or healthcare (n = 150) instructor group. The BLS skill performance passing rate (%) at six months was high in both instructor groups (teacher: 88% versus healthcare: 91%; mean difference: -3%, 95% CI: -11% to 5%; P = 0.22). The students' knowledge levels remained high (>90%) and were similar between instructor groups at six months (P = 0.91). The teachers' willingness to teach BLS to students was mildly positive. However, the students were extremely positive towards learning and performing BLS. Conclusions: A brief 2-hour CO-CPRAED intervention by trained teachers was noninferior to healthcare instructors and it was associated with students' very positive attitudes towards CPR, and retention of knowledge and BLS skills.

Effect of prehabilitation-related DIETary protein intake on Quality of Recovery after elective cardiac surgery (DIETQoR) study: protocol of a randomised controlled trial.

INTRODUCTION: Protein malnutrition is associated with higher risks of postoperative complications, mortality, prolonged postoperative stays in hospital, slower physical and mental recovery after surgery and lower subsequent health-related quality of life. To reduce the risk of postoperative morbidity and mortality, nutritional prehabilitation programmes have been developed recently to build up patient's nutritional reserve to withstand the stress of surgery. The intervention involves nutritional screening and counselling, and increasing dietary protein intake in protein-malnourished patients in the several weeks before surgery. However, there are few well-conducted preoperative studies to examine the effect of increasing dietary protein intake on the quality of recovery of malnourished patients after elective cardiac surgery. METHOD AND ANALYSIS: This randomised controlled trial of malnourished patients undergoing major elective cardiac surgery will compare the quality of postoperative recovery in patients with or without nutritional prehabilitation. One hundred and thirty-two patients will be randomised to receive nutritional prehabilitation (target-adjusted whey protein powder supplementation and an individualised 1 hour session/week counselling by a dietician 1 month before operation date) or standard care (no nutritional prehabilitation). Primary outcomes will be the quality of recovery after surgery (15-item Quality of Recovery) on the third postoperative day. Secondary outcomes will include days (alive and) at home within 30 days, changes in the WHO Disability Assessment Schedule 2.0, changes in health-related quality of life (EQ-5D) and Cardiac Postoperative Morbidity Survey. An outcomes assessor will be blinded to the treatment allocation. Appropriate univariate analyses, generalised estimating equations and multiple regressions will be performed for intention-to-treat and per-protocol analyses. ETHICS AND DISSEMINATION: The Joint CUHK-NTEC Clinical Research Ethics Committee approved the study protocol (CREC Ref. No.: 2021.703 T). The findings will be presented at scientific meetings, peer-reviewed journals and to study participants. TRIAL REGISTRATION NUMBER: ChiCTR2200057463.

Guillain-Barré Syndrome with Rapid Onset and Autonomic Dysfunction Following First Dose of Pfizer-BioNTech COVID-19 Vaccine: A Case Report.

Guillain-Barre syndrome (GBS) is an immune-mediated, often post-infectious illness manifesting as an acute, characteristically monophasic, polyradiculoneuropathy. We present a case of GBS with autonomic involvement following an mRNA-based vaccine against SARS-COV2 (Pfizer/BioNTech mRNA-BNT162b2). A 58-year-old woman presented with fatigue, distal extremity paresthesias, and severe back pain within 3 days after receiving her first vaccine dose. She developed worsening back pain and paresthesias in distal extremities which prompted her initial presentation to the hospital. By the third week post-vaccine, she developed increasing gait unsteadiness, progression of paresthesias, and new autonomic symptoms including presyncopal episodes and constipation. Neurological exam showed bilateral distal predominant lower extremity weakness, decreased sensation in a length-dependent pattern, and areflexia. EMG/NCS showed a diffuse sensorimotor polyneuropathy with mixed demyelinating and axonal features consistent with GBS. She was treated with 2 g/kg of IVIG over 3 days and also received prednisone 60 mg daily for 3 days for severe back pain, with improvement of symptoms. This possible association with mRNA-based vaccination expands the potential triggers for an autoimmune-based attack on the peripheral nervous system.

Ultraviolet photoacoustic microscopy with tissue clearing for high-contrast histological imaging.

Ultraviolet photoacoustic microscopy (UV-PAM) has been investigated to provide label-free and registration-free volumetric histological images for whole organs, offering new insights into complex biological organs. However, because of the high UV absorption of lipids and pigments in tissue, UV-PAM suffers from low image contrast and shallow image depth, hindering its capability for revealing various microstructures in organs. To improve the UV-PAM imaging contrast and imaging depth, here we propose to implement a state-of-the-art optical clearing technique, CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis), to wash out the lipids and pigments from tissues. Our results show that the UV-PAM imaging contrast and quality can be significantly improved after tissue clearing. With the cleared tissue, multilayers of cell nuclei can also be extracted from time-resolved PA signals. Tissue clearing-enhanced UV-PAM can provide fine details for organ imaging.

Effect of a patient education video and prehabilitation on the quality of preoperative person-centred coordinated care experience: protocol for a randomised controlled trial.

INTRODUCTION: Multimodal prehabilitation, an emerging field within the Perioperative Medicine specialty, requires close multidisciplinary team coordination. The goal is to optimise the patient's health status in the 4-8 weeks before elective surgery to withstand surgical stress. Most patients are unfamiliar with the concept of prehabilitation but are interested in participating in such a programme after explanation. The objective of this randomised controlled trial is to evaluate the effect of prehabilitation (patient education video and multimodal prehabilitation) on the preoperative patient-centred coordinated care experience. METHOD AND ANALYSIS: One hundred patients undergoing major elective surgery (cardiac, colorectal, hepatobiliary-pancreatic and urology) will be recruited into a two-group, parallel, superiority, single-blinded randomised controlled trial. Patients will be randomised to receive either preoperative patient education comprising of a video and prehabilitation programme with standard care (intervention) or standard care (control). The primary outcome measure will be the quality of preoperative patient care experience using the 11-item Chinese version of the Person-Centred Coordinated Care Experience Questionnaire (P3CEQ) before surgery. Secondary outcomes will include the change in Hospital Anxiety and Depression Scale (HADS) score from trial enrolment to before surgery, Quality of Recovery Score (QoR-15) on third day after surgery and Days Alive and At Home within 30 days after surgery (DAH30). Intention-to-treat and per-protocol analyses will be performed. ETHICS AND DISSEMINATION: The Joint CUHK-NTEC Clinical Research Ethics Committee approved the study protocol (CREC Ref. No. 2021.518-T). The findings will be presented at scientific meetings, in peer-reviewed journals and to study participants. TRIAL REGISTRATION NUMBER: ChiCTR2100053637.

Late stage complicated atheroma in low-grade stenotic carotid disease: MR imaging depiction--prevalence and risk factors.

PURPOSE: To determine if complicated plaque can be found by using magnetic resonance (MR) imaging-depicted intraplaque hemorrhage (IPH), even among symptomatic patients with low-grade (≤50%) carotid stenosis. MATERIALS AND METHODS: The institutional ethics review board approved this retrospective study and waived requirements for written informed consent. Symptomatic patients with bilateral 0%-50% carotid stenosis referred for carotid MR imaging were considered. Risk factors (age, sex, hypertension, diabetes, hyperlipidemia, myocardial infarction, atrial fibrillation, smoking, coronary artery disease, and cerebrovascular disease), medications (antihypertensive drugs, diabetes drugs, statins, and aspirin), and the brain side causing symptoms were recorded. MR-depicted IPH prevalence in the carotid arteries ipsilateral and contralateral to the symptomatic side was compared by using the Fisher exact test. Multivariable regression was used to compare the MR-depicted IPH prevalence, while adjusting for risk factors and medications. RESULTS: A total of 217 patients (434 carotid arteries) were included. MR-depicted IPH was found in 13% (31 of 233) of carotid arteries ipsilateral and 7% (14 of 201) of arteries contralateral to symptoms (P < .05). Male sex (P < .05) and increasing age (P < .05) were associated with MR-depicted IPH after controlling for risk factors and medications. CONCLUSION: Complicated carotid atheroma can be found among symptomatic patients with low-grade (≤50%) stenosis, and this is associated with male sex and increasing age. MR-depicted IPH may be useful to stratify risk for patients with low-grade carotid stenosis.

A comparison of the systemic toxicity of lidocaine versus its quaternary derivative QX-314 in mice.

PURPOSE: We recently showed that the quaternary lidocaine derivative, QX-314, produces long-lasting local anesthesia with a slow onset in animal models in vivo. As quaternary agents do not rapidly penetrate biological membranes or the blood-brain barrier, QX-314 may represent a local anesthetic with decreased systemic toxicity compared with conventional tertiary aminoamines. To test this hypothesis, we conducted an in vivo animal study in mice to compare QX-314 with lidocaine in terms of its relative central nervous system (CNS) and cardiac toxicity. METHODS: With approval from the institutional Animal Care Committee, we used the "up-and-down" method to determine the relative potencies (ED(50)) of lidocaine and QX-314 for CNS and cardiac toxicity in adult CD-1 mice (weight, 20 to 35 g). The animals were administered either intravenous lidocaine or QX-314 (dose range, 7.5 to 30 mg·kg(-1)) and were observed for signs of CNS toxicity (convulsions, ataxia, loss of righting reflex, and/or death). We also observed animals for electrocardiographic evidence of toxic effects on cardiac automaticity, conductivity, and rhythmicity. RESULTS: The ED(50) of lidocaine for CNS toxicity as determined by the "up-and-down" method was 19.5 mg·kg(-1) (95% confidence interval [CI], 17.7 to 21.3 mg·kg(-1); n = 6) compared with 10.7 mg·kg(-1) for QX-314 (95% CI, 9.1 to 12.3 mg·kg(-1); n = 6) (potency ratio, 1.8). Similarly, the ED(50) of lidocaine for electrocardiographic evidence of cardiac toxicity was significantly higher than that of QX-314 (ED(50) of lidocaine, 21.2 mg·kg(-1); 95% CI, 19.0 to 23.4 mg·kg(-1); n = 6 vs ED(50) of QX-314, 10.6 mg·kg(-1); 95% CI, 8.4 to 12.8 mg·kg(-1); n = 6) (potency ratio, 2.0). CONCLUSIONS: In this in vivo animal study, the relative potencies of QX-314 for systemic CNS and cardiac toxicity were significantly higher than those of lidocaine. These data do not support the hypothesis that QX-314 is a safer local anesthetic compared with lidocaine in terms of systemic toxicity. Whereas our results do not exclude the possibility that QX-314 may represent a clinically useful agent to produce long-lasting local anesthesia and nociceptive blockade after a single shot in humans, its systemic toxicity relative to conventional tertiary aminoamide local anesthetics and the underlying mechanisms warrant further study.

Educational Research: Why Medical Students Choose Neurology: A Computational Linguistics Analysis of Personal Statements.

OBJECTIVE: To understand medical students' motivations for choosing neurology and how applicants conceptualize the field, as this information can be used to enhance interest in neurology and develop educational programs to help identify, support, and recruit future neurologists. BACKGROUND: Applicants to neurology residencies submit personal statements describing themselves and their motivations. Textual analysis of personal statements has been performed in internal medicine and general surgery, but never before in neurology. We hypothesized that specific words and themes would be mentioned in residency personal statements with high frequencies indicating students' motivations. METHODS: We used computational linguistics software to assess key words and thereby study motivations, expectations, and themes present among neurology applicants. A total of 2,405 personal statements submitted over 5 years to our institution were de-identified and compiled into a database for evaluation through 3 computational linguistics software programs. We performed calculations of term frequencies (TF) and TF-inverse document frequencies and performed K-means clustering to identify unique words and common themes. RESULTS: Specific disease states were discussed. For example, stroke (TF 2,178), epilepsy (TF 970), and dementia (TF 944) were referenced more often than amyotrophic lateral sclerosis (TF 220) and carpal tunnel (TF 10). The most common proper names cited were Oliver Sacks (TF 94) and Sherlock Holmes (TF 41). Common themes included fascination with the brain, interest in research, desire to help patients, early interests in neurology, continued pursuit of learning, appreciation for time with patients, family history with neurologic illness, and intellectual curiosity. CONCLUSIONS: This first computational linguistic analysis of neurology personal statements provides understanding into medical students' motivations and interests. Ongoing subgroup and thematic analyses may inform educational strategies and enhance recruitment to our field.