Clinical Evaluation Research Articles

Clinical evaluation of a machine learning-based early warning system for patient deterioration.

The implementation and clinical impact of machine learning-based early warning systems for patient deterioration in hospitals have not been well described. We sought to describe the implementation and evaluation of a multifaceted, real-time, machine learning-based early warning system for patient deterioration used in the general internal medicine (GIM) unit of an academic medical centre. In this nonrandomized, controlled study, we evaluated the association between the implementation of a machine learning-based early warning system and clinical outcomes. We used propensity score-based overlap weighting to compare patients in the GIM unit during the intervention period (Nov. 1, 2020, to June 1, 2022) to those admitted during the pre-intervention period (Nov. 1, 2016, to June 1, 2020). In a difference-indifferences analysis, we compared patients in the GIM unit with those in the cardiology, respirology, and nephrology units who did not receive the intervention. We retrospectively calculated system predictions for each patient in the control cohorts, although alerts were sent to clinicians only during the intervention period for patients in GIM. The primary outcome was non-palliative in-hospital death. The study included 13 649 patient admissions in GIM and 8470 patient admissions in subspecialty units. Non-palliative deaths were significantly lower in the intervention period than the pre-intervention period among patients in GIM (1.6% v. 2.1%; adjusted relative risk [RR] 0.74, 95% confidence interval [CI] 0.55-1.00) but not in the subspecialty cohorts (1.9% v. 2.1%; adjusted RR 0.89, 95% CI 0.63-1.28). Among high-risk patients in GIM for whom the system triggered at least 1 alert, the proportion of non-palliative deaths was 7.1% in the intervention period, compared with 10.3% in the pre-intervention period (adjusted RR 0.69, 95% CI 0.46-1.02), with no meaningful difference in subspecialty cohorts (10.4% v. 10.6%; adjusted RR 0.98, 95% CI 0.60-1.59). In the difference-indifferences analysis, the adjusted relative risk reduction for non-palliative death in GIM was 0.79 (95% CI 0.50-1.24). Implementing a machine learning-based early warning system in the GIM unit was associated with lower risk of non-palliative death than in the pre-intervention period. Machine learning-based early warning systems are promising technologies for improving clinical outcomes.

Abstract PR-16: Evaluating direct KRASQ61H inhibition in pancreatic cancer models

Abstract KRASQ61 mutations are associated with the worst prognosis among the various KRAS mutational subtypes of pancreatic ductal adenocarcinoma (PDAC). RMC-7977 is a RAS(ON) multi-selective noncovalent inhibitor with broad spectrum activity against oncogenic RAS mutants and wild-type RAS. The related investigational agent RMC-6236 is currently undergoing clinical trials. Binary complexes of CypA: RMC-7977 bind equipotently to multiple KRAS mutational subtypes however RMC-7977 is less potent at inhibiting growth in KRASQ61H-mutant cell lines. In contrast, RM-047 is a preclinical RAS(ON) Q61H-selective inhibitor tool compound. We evaluated direct KRASQ61H inhibition using both RMC-7977 and RM-047 in cell culture models. We found that in KRASQ61H-rescued RASless mouse embryonic fibroblasts (MEFs), RM-047 inhibited ERK activity and suppressed growth more potently than RMC-7977. Conversely, in a panel of KRASQ61H-mutant PDAC cell lines, RM-047 was less potent than RMC-7977 in two out of three KRASQ61H-mutant PDAC cell lines. Furthermore, we discovered that ERK activity rapidly rebounded with treatment in KRASQ61H-mutant PDAC cell lines, whereas ERK activity remained suppressed in KRASQ61H-rescued RASless MEFS lacking WT RAS alleles. Our analysis of DepMap data indicated that among the KRAS mutational subtypes frequently found in pancreatic cancer, KRASQ61H is the least dependent on KRAS for survival. This suggests that in a KRASQ61H-mutant PDAC setting, additional factors such as WT RAS expression may mediate growth. From our KRAS drug-anchored CRISPR loss-of-function screens, we found that the loss of EGFR sensitized cells to KRAS inhibition, particularly in a KRASQ61H-dependent context. Therefore, we combined erlotinib, an FDA-approved EGFR inhibitor, with either RM-047 or RMC-7977, and found that the addition of erlotinib prevented ERK rebound activity and synergized with RM-047 or RMC-7977 to reduce growth in KRASQ61H-mutant PDAC cell lines. These data provide insights into mechanisms by which KRASQ61H-mutant PDAC may be less dependent on KRAS for survival and further support the clinical evaluation of combined EGFR and RAS(ON) inhibition as a potential therapeutic strategy in the treatment of PDAC patients harboring KRASQ61H mutations. Citation Format: Szu-Aun Long, Amber M Amparo, Haley Todd, Grace Goodhart, Syed A Ahmad, Andrew M Waters. Evaluating direct KRAS inhibition in pancreatic cancer models [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr PR-16.

The Role of Contrast-enhanced Ultrasound in the Femoral Head Perfusion Evaluation: A Pilot Study

ObjectivesWe explored the value of contrast-enhanced ultrasound (CEUS) in evaluating femoral head (FH) perfusion, guiding interventions and follow-up for infants with developmental dysplasia of the hip (DDH) and septic arthritis of the hip (SAH). The aim was to provide robust evidence for clinical assessment. MethodsTen infants, including 7 with DDH and 3 with SAH, were prospectively enrolled, with their bilateral hips alternately scanned during the CEUS exams. Twenty hips were classified into the case group (n = 11) and the control group (n = 9). Pre- and post-interventional studies were performed in DDH infants requiring interventions. FH perfusion was assessed by the perfusion area ratio (PAR) and quadrant location of microbubble-defect regions. ResultsIn the case group, 25 CEUS studies were conducted, including 11 baseline, 7 follow-up and 7 post-intervention studies. The PAR significantly decreased in the case group (49.79% vs. 100.00%, p < 0.05). The microbubble-defect regions averagely affected 2 quadrants, primarily quadrat No. 3 (30%) and No. 4 (32%). Seven hip abduction angle adjustments were made based on pre-interventional studies, resulting in a significant increase in PAR in post-interventional studies (37.63% vs. 60.24%, p < 0.05). PAR increased in follow-up studies compared to baseline values (45.61% vs. 76.07%, p < 0.05). The inter- and intra-observer reproducibility of PAR measurements were excellent (intraclass correlation coefficient, both 0.97). ConclusionCEUS proves to be a promising technique for quantitatively detecting FH perfusion in DDH and SAH infants with high reproducibility. It is valuable for baseline, intra-intervention and follow-up studies, aiming in clinical conditions and therapeutic effect evaluation.

Restoring of interhemispheric symmetry in patients with stroke following bilateral or unilateral robot-assisted upper-limb rehabilitation: a pilot Randomized Controlled Trial.

Bilateral robotic rehabilitation has proven helpful in the recovery of upper limb motor function in patients with stroke, but its effects on the cortical reorganization mechanisms underlying recovery are still unclear. This pilot Randomized Controlled Trial (RCT) aimed to evaluate the effects on the interhemispheric balance of unilateral or bilateral robotic treatments in patients with subacute stroke, using Quantitative Electroencephalography (qEEG). 19 patients with ischemic stroke underwent a 30-session upper limb neurorehabilitation intervention using a bilateral upper limb exoskeleton. Each patient was randomly assigned to the bilateral (BG, n=10) or unilateral treatment group (UG, n=9). EEG evaluations were performed before (T0) and right after (T0+) the first treatment session, after 30 treatment sessions (T1), and at 1-week follow-up (T2), in both eyes open and eyes closed conditions. From the acquired EEG data, the pairwise-derived Brain Symmetry Index (pdBSI) was computed. In addition, clinical evaluation was performed at T0 and T1 with validated clinical scales. After the treatment, a significant improvement in clinical and EEG evaluations was observed for both groups, but only the BG showed reduced pdBSI in delta and theta bands. In the cluster of sensorimotor channels, there was no significant difference between groups. The observed changes were not maintained at follow-up. No significant changes were observed in the pdBSI after a single rehabilitation session. Results suggest that balancing of interhemispheric symmetry comes along with a clinical improvement in the upper extremity and that the pdBSI can be used to investigate the mechanisms of neuronal plasticity involved in robotic rehabilitation after stroke.

Clinical and radiographic evaluation of Ga-Al-As diode in immature permanent mandibular first molars direct pulp capping: A 12-month randomized controlled clinical trial

Clinical and radiographic evaluation of Ga-Al-As diode in immature permanent mandibular first molars direct pulp capping: A 12-month randomized controlled clinical trial

Ultrasound biomicroscopy qualitative and quantitative signs of phacoantigenic uveitis.

To describe the ultrasound biomicroscopy (UBM) diagnostic features in patients suspected of experiencing chronic inflammation due to phacoantigenic uveitis SUBJECTS/METHODS: This single-center study enrolled patients referred to the Uveitis Department of Cleveland Clinic Abu Dhabi for chronic anterior uveitis and traumatic cataract. Patients' demographics, causes and dates of the inciting traumatic event, and ophthalmic findings were recorded. 20-MHz UBM assessment of the status of the anterior capsule and the crystalline lens was performed. Then, cataract surgery was performed using a single technique. Comparison of the anterior capsule and lens status by clinical, UBM, and intraoperative evaluation. Forty eyes with phacoantigenic uveitis were considered. The slit-lamp examination could identify interruption of the anterior capsule in 20% of the eyes and liquefied sinking lens material in 10%. An intra-operative defect in the anterior capsule was documented in 87.5% of eyes. UBM imaging showed anterior capsule irregularity in 63.3% of eyes and confirmed the presence of anterior capsule defects in 47.5% and lens matter herniating into the anterior chamber in 15%. Hypoechogenic lacunae within the cataractous lens were detected in 12.5% of eyes. For UBM, sensitivity and specificity values were 82.86% (95% CI: 66.35-93.44) and 100% (95% CI: 47.82-100), respectively. Positive and negative predictive values for UBM were 100% (95% CI: 88.06-100) and 45.45% (95% CI: 28.69-63.32), respectively. The overall diagnostic accuracy of UBM was 85% [95% CI: 70.16-94.29]. Ultrasound Biomicroscopy (UBM) is essential for assessing suspected anterior capsule ruptures in phacoantigenic uveitis cases.

Deep learning-based segmentation for high-dose-rate brachytherapy in cervical cancer using 3D Prompt-ResUNet.

To develop and evaluate a 3D Prompt-ResUNet module that utilized the prompt-based model combined with 3D nnUNet for rapid and consistent autosegmentation of high-risk clinical target volume and organ at risk in high-dose-rate brachytherapy for cervical cancer patients. &#xD;Approach. We used 73 computed tomography (CT) and 62 magnetic resonance imaging (MRI) scans from 135 (103 for training, 16 for validation, and 16 for testing) cervical cancer patients across two hospitals for HRCTV and OAR segmentation. A novel comparison of the deep learning neural networks 3D Prompt-ResUNet, nnUNet, and SAM-Med3D was applied for the segmentation. Evaluation was conducted in two parts: geometric and clinical assessments. Quantitative metrics included the Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95%), Jaccard index (JI), and Matthews correlation coefficient (MCC). Clinical evaluation involved interobserver comparison, 4-grade expert scoring, and a double-blinded Turing test.&#xD;Main results. The Prompt-ResUNet model performed most similarly to experienced radiation oncologists, outperforming less experienced ones. During testing, the DSC, HD95% (mm), JI, and MCC value (mean ± SD) for HRCTV were 0.92±0.03, 2.91 ± 0.69, 0.85± 0.04, and 0.92 ± 0.02, respectively. For the bladder, these values were 0.93 ± 0.05, 3.07 ± 1.05, 0.87 ± 0.08, and 0.93 ± 0.05, respectively. For the rectum, they were 0.87 ± 0.03, 3.54 ± 1.46, 0.78 ± 0.05, and 0.87 ± 0.03, respectively. For the sigmoid, they were 0.76 ± 0.11, 7.54 ± 5.54, 0.63 ± 0.14, and 0.78 ± 0.09, respectively. The Prompt-ResUNet achieved a clinical viability score of at least 2 in all evaluation cases (100%) for both HRCTV and bladder and exceeded the 30% positive rate benchmark for all evaluated structures in the Turing test.&#xD;Significance. The Prompt-ResUNet architecture demonstrated high consistency with ground truth (GT) in autosegmentation of HRCTV and OARs, reducing interobserver variability and shortening treatment times.&#xD.

B - 118 Exploration of Supplemental Recognition Measures for the RBANS

Abstract Objective RBANS is a widely used cognitive screener that lacks memory recognition measures for 2 recall tasks. Performance on verbal and visual recognition measures, relative to recall, may help inform clinical decision-making and treatment planning. Our pilot project aims to understand how individuals with valid cognitive data and normal memory functioning perform on newly developed RBANS story and figure memory recognition tests. Method Of those referred for outpatient neuropsychological assessment at a veterans hospital between 2017–2024, 89 received the newly established recognition measures as part of their clinical evaluation. Our analysis included veterans that displayed valid profiles (TOMM trial 1 ≥ 45, n = 53). Assessment occurred 30% face-to-face and 70% telehealth. In addition to key demographic factors listed in table 1, race/ethnicity breakdown included: 92% White, 4% Black, 2% Asian, 2% Hispanic. These veterans were subdivided into 3 intact memory groups: list recall (≥ 25%ile, n = 31), story recall (≥ 25%ile, n = 37), figure recall (≥ 25%ile, n = 42) to determine average recognition performances across domains. Results The individuals with valid cognitive data and normal memory recall performed as listed in table 1. Although our novel story and figure recognition measures differ from those published in Duff et al. (2021), our pilot project data largely overlapped with their reported findings despite demographic differences. Conclusion(s) These novel recognition scores can help establish normal story and figure recognition performance to assist with clinical diagnosis and treatment planning. With greater and more diverse samples, we may be able to establish relative cut points for expected recognition memory performances across intact, amnestic/cortical, and vascular/subcortical.

Traumatic Brain Injury and Risk of Incident Dementia: Forensic Applications of Current Research

Abstract Objective Traumatic Brain Injury (TBI) has been purported to increase risk for later developing neurodegenerative disorders (ND). Forensic neuropsychologists are frequently asked to opine on risk for ND after an alleged TBI. We provide an evidence-based foundation to aid forensic practice by summarizing the: role of the neuropsychologist in TBI-related litigation, complexities associated with identifying TBIs in forensic cases, science of TBI in relation to incident dementia, and current scientific evidence for chronic traumatic encephalopathy. Data Selection The most applicable studies to forensic settings are large prospective cohort and population-based cohort studies given their wider generalizability and long periods of follow-up/tracking for outcomes. Data Synthesis Developing ND after TBI is the exception rather than the rule. Only a small subset (&amp;lt; 5%) of individuals with moderate-to-severe TBI, and even fewer (&amp;lt; 1%) with mild TBI, appear to develop ND, and the characteristics that place some at risk remain unclear. Positive evidence for risk of ND after mild TBI is weak and mostly consists of observational studies characterized by methodological limitations. Conclusions Forensic methods used to establish the likely occurrence of TBI are typically more extensive than those used in clinical evaluations, while TBI definitions used in current research are even more rudimentary and inconsistent. Applying clinical research findings regarding TBI and dementia outcomes to forensic cases at an individual level carries significant limitations. Estimating the contribution of remote TBI/concussion in a causal manner to ND risk is a challenge forensic experts sometimes face, yet at present, the task is impossible beyond correlations and speculation.

B - 6 The BRIEF-2A Pattern of Self and Informant Executive Functioning Difficulties in Adults with Epilepsy

Abstract Objective People with epilepsy (PWE) commonly have executive functioning (EF) difficulties on objective testing. However, less is known about subjective EF difficulties in everyday life. We examined self- and informant-rated EF in PWE using the Behavior Rating Inventory of Executive Function for Adults-2 (BRIEF-2A). We hypothesized that PWE and their informants would endorse greater EF difficulties relative to healthy participants. Method Participants included 43 PWE who completed comprehensive clinical neuropsychological evaluation at a large Northeastern academic medical center, which included BRIEF-2A Informant and Self Report Forms (Age M = 40.4 ± 17.2 years, 53% female, Education M = 13.0 ± 1.8 years). Twenty-four participants completed self-reports, while 19 had both self and informant reports. The comparison sample included 43 age- and gender-matched healthy controls (HC). We analyzed BRIEF-2A subscales using MANOVAs, where elevated T scores indicated worse EF. Repeated measures ANOVAs compared self and informant ratings. Multi-rater comparisons (90% CIs) and chi-squares analyzed patterns of discrepant ratings. Results Self-reported EF difficulties in PWE were elevated across all scales, compared to HC (p’s0.25), with greatest difference observed for working memory (PWE = 69.7 ± 12.7, HC = 44.5 ± 16.7, ηp2 = 0.61). Similar elevations across all scales were observed for PWE informant reports (p’s0.14). PWE rated greater self-monitoring (p = 0.03, ηp2 &amp;gt; 0.23) and emotional control (p = 0.08, ηp2 &amp;gt; 0.16) difficulties than informants. There was 42.1–68.4% concordance between self and informant reports for PWE, compared to 84–95% in HC. Patterns of self and informant ratings were similar between PWE and HC for initiation, planning/organization, and task-monitoring (p’s &amp;gt; 0.20). Conclusions PWE and their informants report high, yet relatively similar, levels of EF difficulties in daily life.

B - 99 Timely Matters: Processing Speed and Other Cognitive Corelates of Identi-Fi Accuracy and Time to Completion

Abstract Objective The Identi-Fi is a test of visuospatial organization with overall performance represented by the Visual Organization Index (VOI). Though untimed, the Professional Manual indicates administration takes ~10 minutes in the standardization sample. We examined Identi-Fi time of completion (TOC) in a mixed clinical sample and explored whether TOC and VOI are differentially associated with other neuropsychological measures. Method Participants were 240 adults referred for clinical neuropsychological evaluation, 78.3% being aged 60+ (M = 64.50 ± 12.38 years, range = 21–79), male (54.6%), with 14.80 ± 2.89 years of education (range = 7–21). They completed the Identi-Fi and other cognitive tests (WAIS-IV Block Design and Digit Span; Trail Making Test; Boston Naming Test; D-KEFS Color-Word Interference). Correlation and linear regression were used to examine relationships. Results Overall, VOI was low average (M = 85.61 ± 19.00, range = 40–125). TOC was slightly longer (M = 12.92 ± 6.04 minutes, range = 4.07–47.78) than reported in the manual. VOI was correlated with visuoconstruction, confrontation naming, attention, processing speed and executive functions (all p ≤ 0.001), as well as TOC (r = −0.195, p = 0.002) and education (r = 0.136, p = 0.035). TOC was corelated with age (r. = 384, p &amp;lt; 0.001), education (r = 0.141, p = 0.029), processing speed (TMT-A: r = −0.329, p &amp;lt; 0.001; CW1: r = −0.171, p = 0.014), cognitive flexibility (r = −0.230, p = 0.001), and response inhibition (r = −0.269, p &amp;lt; 0.001). TOC was predicted by processing speed (β = −4.986, p = 0.049) even after accounting for age and education. Conclusion TOC may be longer in clinical populations, though this may reflect the older age of this sample. Although time and accuracy on the Identi-Fi correlated with processing speed, accuracy was also associated with other cognitive abilities. Further research into the clinical utility of Identi-Fi TOC is warranted.

B - 145 CVLT-3 Forced Choice Recognition Failure Rate in a Mixed Clinical Population

Abstract Objective The CVLT-3 is a measure of verbal learning and memory used extensively in clinical and research settings that contains an embedded performance validity indicator, a forced choice recognition trial (CVLT-3-FCR). The CVLT-2-FCR was modified for the CVLT-3-FCR, replacing abstract with concrete distractor words. To date, no one has reported independent data on failure rates in clinical populations on the CVLT-3-FCR. Method Participants were 373 patients referred for clinical neuropsychological evaluation who completed the CVLT-3 (Standard form) as part of their evaluation. Mean age was 61.20 (SD = 14.30, range = 20–86), mean education was 15.00 years (SD = 2.87, range = 6–21), 53.1% were male, and 97.6% White. Failure was defined as CVLT-3-FCR score ≤ 14. Results 85.5% of our mixed clinical sample had CVLT-3-FCR score of 16/16, and 7.5% had 15/16. Only 7% (N = 26) scored ≤14, most common primary diagnoses being mild neurocognitive disorder (N = 9) and psychiatric (N = 7), while only four had dementia of any etiology. Those who failed tended to be a little older [pass = 60.82 years (SD = 14.44), fail = 66.38 years (SD = 11.28); p = 0.055) and scored lower for CVLT-3 Total Trials 1–5, short- and long-delay free recall, recognition hits, false positives, and discriminability (all p &amp;lt; 0.001). Conclusions Findings indicate CVLT-3-FCR ≤ 14 is extremely rare in a large mixed clinical sample of adults and older adults, even in subsamples for whom lower scores on PVTs have been suggested (e.g., dementia). While passing the CVLT-3-FCR does not in itself confirm adequate test engagement, failure should raise concern and the need for additional PVTs in one’s assessment.

Vasculitis associated with psoriatic arthritis: a case report

BackgroundPsoriatic arthritis is a chronic inflammatory condition associated with psoriasis, which affects joints. The coexistence of vasculitis, an inflammation of blood vessels, with psoriatic arthritis is rare, highlighting a complex interplay between autoimmune diseases that affect both joints and vascular structures.Case presentationWe report on a 56-year-old male with a long-standing history of psoriasis and psoriatic arthritis, who presented with new-onset skin lesions and neurological symptoms. Clinical evaluations confirmed the presence of leukocytoclastic vasculitis and asymmetric sensory motor axonal neuropathy. The absence of positive results from various standard tests led to a challenging diagnostic process, ultimately pointing towards vasculitis associated with psoriatic arthritis. The patient was treated with corticosteroids and immunosuppressive therapy, leading to partial symptom improvement.ConclusionsThis case underlines the complex and often overlapping nature of autoimmune conditions, particularly the occurrence of vasculitis in patients with psoriatic arthritis, which is rare. It stresses the importance of considering vasculitis in patients with psoriatic arthritis who present with unexplained skin lesions and neurological symptoms. This case adds to the spectrum of psoriatic disease manifestations and suggests a need for further research to explore the underlying mechanisms and improve management strategies.

Construction d’une méthodologie d’évaluation clinique des dispositifs médicaux grâce aux outils de simulation et illustration à travers trois études

European regulations have recently moved towards more stringent requirements for demonstrating the safety and performance of medical devices (MDs). To apply an innovative testing method using medical simulation to the evaluation of three medical devices at different stages of their life cycle. The methodology for evaluating DMs using simulation is based on seven stages: definition of the context, training, construction of a scenario to test the DM, validation of the scenario, realization of the scenario, evaluation of the scenario by the players and validation and exploitation of the results. Our evaluation methodology enabled us to assess three DMs at different stages of their development: a respiratory protection device at the initial stage (prototype definition), a respiratory protection mask (prototype optimization) and bottle adapters (post-marketing). Simulation is a valuable tool for evaluating DM. The proposed methodology enables it to be used and adapted to different contexts. It responds to the specificities of clinical evaluation of this class of products, and helps to better anticipate certain risks.

Improving the quality of clinical training in maternal and neonatal health in undergraduate nursing students: a participatory action research

BackgroundImproving the quality of clinical training is synonymous with accomplishing nursing education goals and improving the quality of nursing care. This study aimed to improve the quality of clinical training in Maternal and Neonatal Health (MNH) in nursing students.MethodsThis action research was conducted in two cycles from June 2017 to June 2018. The study setting was the School of Nursing and Midwifery of Lorestan University of Medical Sciences in southwest Iran. The participants were nursing students, faculty members, clinical trainers, educational managers, and teaching personnel. In the first cycle, semi-structured interviews were held with stakeholders to identify clinical problems and improvement strategies. Based on the results of these sessions, the changes needed to improve the quality of clinical training were planned and implemented. The weaknesses and strengths of the implemented changes were then identified through group discussions with the stakeholders. In the second cycle, a second plan was carried out to correct the weaknesses of the changes planned in the first cycle, and the modifications were implemented and evaluated.ResultsThe main three categories extracted included an unsystematic curriculum and inadequate monitoring, inadequate resources and facilities, and the student’s lack of motivation. The measures taken for improvement included holding communication workshops, developing and internalizing logbooks, reducing the number of students in clinical training groups, using modern clinical training methods, and changing clinical evaluation methods.ConclusionImproving communication skills among the students, trainers, and hospital personnel and using modern clinical training methods, such as conceptual maps, triple jumps, and clinical skill centers, are the best strategies for improving clinical training in MNH nursing students.

Clinical evaluation of a highly multiplexed CRISPR-based diagnostic assay for diagnosing lower respiratory tract infection: a prospective cohort study

Objective Accurate and rapid identification of causative pathogens is essential to guide the clinical management of lower respiratory tract infections (LRTIs). Here we conducted a single-centre prospective study in 284 patients suspected of lower respiratory tract infections to evaluate the utility of a nucleic acid test based on highly multiplexed polymerase chain reaction (PCR) and CRISPR-Cas12a. Methods We determined the analytical and diagnostic performance of the CRISPR assay using a combination of reference standards, including conventional microbiological tests (CMTs), metagenomic Next-Generation Sequencing (mNGS), and clinical adjudication by a panel of experts on infectious diseases and microbiology. Results The CRISPR assay showed a higher detection rate (63.0%) than conventional microbiological tests (38.4%) and was lower than metagenomic Next-Generation Sequencing (72.9%). In detecting polymicrobial infections, the positivity rate of the CRISPR assay (19.4%) was higher than conventional microbiological tests (3.5%) and lower than metagenomic Next-Generation Sequencing (28.9%). The overall diagnostic sensitivity of the CRISPR assay (67.8%) was higher than conventional microbiological tests (41.8%), and lower than metagenomic Next-Generation Sequencing (93.2%). Conclusions Considering the low cost, ease of operation, short turnaround time, and broad range of pathogens detected in a single test, the CRISPR assay has the potential to be implemented as a screening tool for the aetiological diagnosis of lower respiratory tract infections patients, especially in cases where atypical bacteria or coinfections are suspected.

Fibrosis, biomarkers and liver biopsy in AAT deficiency and relation to liver Z protein polymer accumulation.

The course of adults with ZZ alpha-1-antitrypsin deficiency (AATD) liver disease is unpredictable. The utility of markers, including liver biopsy, is undefined. A prospective cohort, including protocol liver biopsies, was enrolled to address these questions. We enrolled 96 homozygous ZZ AATD adults prospectively at three US sites with standardized clinical evaluations, and protocol liver biopsies. Fibrosis was scored using Ishak (stages 0-6). Also, 51% of the 96 subjects had Ishak score >1 fibrosis (49% Ishak 0-1, 36% Ishak 2-3 and 15% ≥4). Elevated aspartate aminotransferase (AST) more than alanine aminotransferase (ALT), high body mass index (BMI), obesity, AST platelet ratio index and elevated serum Z alpha 1 antitrypsin (AAT) polymer levels were associated with increased fibrosis. Steatosis did not correlate to fibrosis. Increased fibrosis was associated with increased mutant Z polymer globular inclusions (p = .002) and increased diffuse cytoplasmic Z polymer on biopsy (p = .0029) in a direct relationship. Increased globule Z polymer was associated with increased serum AST (p = .007) and increased periportal inflammation on histopathology (p = .004), but there was no relationship of Z polymer hepatocellular accumulation with ALT, gamma glutamine transferase, inflammation in other parts of the lobule, necrosis or steatosis. Serum Z polymer levels were directly correlated to hepatic Z protein polymer content. Lung function, smoking and alcohol consumption patterns were not associated with fibrosis. In AATD high BMI, obesity and elevated AST are associated with increased fibrosis. Liver biopsy features are correlated to some serum tests. Serum Z AAT polymer levels could be a future biomarker to detect fibrosis early and is directly correlated to liver Z content.

Primary Conjunctival Molluscum Contagiosum in a Patient With Ocular Graft-Versus-Host Disease.

Primary conjunctival molluscum contagiosum (MC) is rare and usually reported in patients with acquired immunodeficiency syndrome. In this study, we present a case of bilateral primary conjunctival MC in a patient with ocular graft-versus-host disease (oGVHD). This is a case report study. Clinical evaluation, in vivo confocal microscopy imaging, and histopathology were used to confirm the diagnosis. A 38-year-old woman with a history of allogeneic bone marrow transplant and secondary chronic oGVHD presented with ocular discomfort, redness, and dryness. On examination, clusters of white gelatinous nodular lesions, stained with fluorescein and Lissamine green, were observed on the bulbar conjunctiva, along with similar solitary nodular lesions in all quadrants of both eyes. In vivo confocal microscopy revealed nests of epithelial cells with bright inclusions measuring approximately 30-35 μm. Excisional biopsy confirmed the diagnosis of MC. A 6-month post-operative follow-up showed healed conjunctiva with no recurrence and improved ocular comfort. Molluscum contagiosum should be considered in the differential diagnosis of conjunctival lesions in patients with impaired immunity such as oGVHD. In diagnosing MC lesions, in vivo confocal microscopy proves to be valuable. In the absence of topical antiviral treatment, surgical excision is warranted.

Music Perception and Music-Related Quality of Life in Adult Cochlear Implant Users: Exploring the Need for Music Rehabilitation.

Cochlear implant (CI) users face difficulties in accurately perceiving basic musical elements such as pitch, melody, and timbre. Music significantly affects the quality of life (QoL) of CI users. Individually and culturally influenced music perception exceeds psychophysical measures in capturing the subjective music enjoyment of CI users. Understanding the music perception, enjoyment, and habits of CI users is crucial for approaches to improve music-related QoL (MuRQoL). Therefore, this study aims to investigate music perception skills, experiences, and participation in music activities in a large group of adult CI users, and to understand the importance of these factors and their impact on QoL of CI users. This study included 214 CI recipients with diverse auditory experiences who were aged between 18 and 65 years and were unilateral, bimodal, or bilateral users for at least 1 year and 193 normal hearing (NH) controls. All participants completed the information forms and the MuRQoL questionnaire. To assess the impact of music on QoL and identify personalized rehabilitation needs, the scores for each question in both parts of the questionnaire were intersected on a matrix. Data were presented in detail for the CI group and compared between CI and NH groups. A statistically significant difference was found between the matched CI and NH groups in favor of the NH group in terms of music perception and music engagement. Participants who received music education at any point in their lives had significantly higher MuRQoL questionnaire scores. There was no significant relationship found between the duration of auditory rehabilitation, pre-CI hearing aid usage, music listening modality, and MuRQoL questionnaire scores. Unilateral CI users had significantly lower scores in music perception and music engagement subsections compared with bimodal and bilateral CI users. Also, it was found that music had a strong negative impact on QoL in 67/214 of the CI users. Although CI users scored significantly lower than NH individuals on the first part of the questionnaire, which asked about musical skills, enjoyment, and participation in musical activities, findings suggest that CI users value music and music enjoyment just as much. The study reveals the influence of factors such as education level, age, music education, type of hearing loss and auditory rehabilitation on music perception, music enjoyment, and participation in music activities through self-report. The results indicate that for many CI users, music has a strong negative impact on QoL, highlighting the need for personalized music interventions, the inclusion of self-report questionnaires, and music perception tests in clinical evaluations.

Sialylation-associated long non-coding RNA signature predicts the prognosis, tumor microenvironment, and immunotherapy and chemotherapy options in uterine corpus endometrial carcinoma

BackgroundSialylation in uterine corpus endometrial carcinoma (UCEC) differs significantly from apoptotic and ferroptosis pathways. It plays a crucial role in cancer progression and immune response modulation. Exploring how sialylation affects tumor behavior and its link with long non-coding RNAs (lncRNAs) may provide new insights into UCEC prognosis and treatment.MethodsWe obtained RNA transcriptome, clinical, and mutation data of UCEC samples from the TCGA database. Our approach involved developing a risk model based on the co-expression patterns of sialylation genes and lncRNAs. Prognostic lncRNAs were identified through Cox regression and further refined using LASSO analysis. To understand the biological functions and pathways of model-associated differentially expressed genes (MADEGs), we conducted enrichment analyses. We also assessed the immune infiltration status of MADEGs using eight different algorithms, which helped in evaluating the potential for immunotherapy. Additionally, we validated the expression of these lncRNAs in UCEC using cell lines and clinical samples.ResultsWe developed a UCEC risk model using five sialylation-related lncRNAs (AC004884.2, AC026202.2, LINC01579, LINC00942, SLC16A1-AS1). This model, confirmed through Cox analysis and clinical evaluation, effectively predicted patient outcomes. Survival data analysis across entire cohort, as well as within training and test groups, indicated better survival in low-risk UCEC patients. Enrichment analyses linked MADEGs to sialylation functions and cancer pathways. High-risk patients showed increased responsiveness to immune checkpoint inhibitors (ICIs), as indicated by immunological assessments. Subgroup C2 patients showed superior outcomes and a robust response to immunotherapy and chemotherapy. Notably, LINC01579, LINC00942, and SLC16A1-AS1 were significantly overexpressed in UCEC clinical tumor samples as well as in Ishikawa and HEC-1-B cell lines, compared to the normal groups.ConclusionsThis lncRNA signature associated with sialylation could guide prognosis, enhance the understanding of molecular mechanisms, and inform treatment strategies in UCEC. It highlights the potential for the use of ICIs and chemotherapy.