Functional Assessment Tool Research Articles

Impact of preoperative quantitative flow ratio on long term coronary artery bypass grafts patency

Abstract Background Preoperative fractional flow reserve (FFR) in the native coronaries is a known predictor of long-term graft patency after coronary artery bypass graft (CABG) surgery. Quantitative flow ratio (QFR) is an angiogram-based functional assessment tool of coronary stenoses. Its predictive value of graft patency is unknown. Purpose To investigate the impact of preoperative QFR value on long-term graft patency after CABG. Methods In this retrospective multicentric study we included consecutive patients treated with CABG between 2011 and 2022, with available coronary angiogram before and at any timepoint after CABG. Three-vessel QFR analysis of the preoperative angiography has been performed. Follow-up angiography was checked for graft patency. Only vessels entered the analysis for which baseline QFR was appropriate and which has been bypassed. Results 400 patients were included with mean age of 67±8 years. They received on average 2.0±0.9 bypasses. 788 coronaries and bypasses were analyzed, among the latter 455 were arterial and 333 were veins. 37% were placed on LAD, 26% on RCA and 26% on the LCx. Stenosis severity at baseline was 73±22% with a QFR value of 0.68±0.30. Follow-up angiographies were performed at 34±29 months. Overall graft patency was 83%, with higher occlusion rate for venous than arterial conduits (27% vs 9%, respectively; HR 3.9 [2.60-5.88]). Occlusion rate was lower for grafts implanted on QFR significant native vessels versus those, placed on non-significant ones (13% vs 30%, respectively; HR 2.86 [1.93-4.26]). Benefit was maintained for both, arterial (5% vs 22%, respectively; HR 5.23 [2.78-10.38]), as well as for venous conduits (24% vs 39%; HR 2.09 [1.21-3.50]). Conclusion QFR significantly predicts graft patency irrespective of whether the graft is arterial or venous. However, patency of venous grafts is poor, even if implanted on functionally significant native stenotic coronaries.Graft patency

Towers of Kuwait Arabic Neurocognitive Assessment: A novel executive and visuospatial functions assessment tool added to the CERAD neuropsychological battery-Arabic version (CERAD-ArNB)

Assessment of executive and visuospatial neurocognitive domains is lacking in the Omani population, especially for elderly individuals with low educational levels. Therefore, the Towers of Kuwait-Arabic Neurocognitive Assessment (ToK-ArNA) was developed using similar psychometric features of Tower of London (ToL) test, and the unique architecture of Towers of Kuwait, with the potential to overcome the limitation of ToL color perception difficulties that might be encountered in subjects with hereditary or acquired color vision disorders. We enrolled 120 older Arabic-speaking Omanis from January 2022 to November 2022 and all participants underwent screening to ensure normal cognitive function before performing the ToL and ToK-ArNA tests. Validity, reliability, and non-parametric statistical tests were used for data analysis. A total of 85 participants, 51 men (60%) and 34 women (40%) met the inclusion criteria and completed the testing. Statistical analyses confirmed the validity and reliability of ToK-ArNA compared to ToL, with comparable total Time and Accuracy scores and more preference towered the ToK-ArNA among the participants. Despite the study limitations, these results indicate that the ToK-ArNA is a reliable and applicable executive and visuospatial function assessment tool and further studies are warranted to establish its validity in patients with various neurocognitive disorders

Spatiotemporal characteristics of eustachian tube development in C57BL/6 mice: Correlation between morphological and functional maturation.

The eustachian tube (ET), a critical conduit connecting the middle ear and nasopharynx, is essential for normal middle ear function. However, it remains one of the least understood anatomical structures due to its complexity and the challenges of in vitro manipulation. Historically, these challenges have hindered research into the morphology and function development of the ET. This study elucidates the spatiotemporal relationship of ET morpho-functional maturation in mice, identifying key periods and factors that lay the theoretical foundation for exploring the molecular mechanisms of ET-related diseases. We comprehensively characterized the ET development in C57BL/6 mice from embryonic day (E) 12.5 to postnatal day (P) 30, focusing on the development of cilia, secretory cells, surrounding glands, and macrophages. Immunostaining identified the localization and secretion patterns of the mucins Muc5b and Muc5ac within the ET. Additionally, using improved ET function assessment tools, we evaluated the developmental features of ET mucociliary clearance and ventilation functions. In C57BL/6 mice, E16.5 marks a critical period for middle ear cavity and ET formation. Muc5b plays a foundational role during early stages, while Muc5ac enhances function in later stages. During P7-11, despite morphological maturity, ET function remains underdeveloped but continues to improve with growth.

Older Adult Fall Risk Prediction with Deep Learning and Timed Up and Go (TUG) Test Data.

Falls are a major health hazard for older adults; therefore, in the context of an aging population, predicting the risk of a patient suffering falls in the near future is of great impact for health care systems. Currently, the standard prospective fall risk assessment instrument relies on a set of clinical and functional mobility assessment tools, one of them being the Timed Up and Go (TUG) test. Recently, wearable inertial measurement units (IMUs) have been proposed to capture motion data that would allow for the building of estimates of fall risk. The hypothesis of this study is that the data gathered from IMU readings while the patient is performing the TUG test can be used to build a predictive model that would provide an estimate of the probability of suffering a fall in the near future, i.e., assessing prospective fall risk. This study applies deep learning convolutional neural networks (CNN) and recurrent neural networks (RNN) to build such predictive models based on features extracted from IMU data acquired during TUG test realizations. Data were obtained from a cohort of 106 older adults wearing wireless IMU sensors with sampling frequencies of 100 Hz while performing the TUG test. The dependent variable is a binary variable that is true if the patient suffered a fall in the six-month follow-up period. This variable was used as the output variable for the supervised training and validations of the deep learning architectures and competing machine learning approaches. A hold-out validation process using 75 subjects for training and 31 subjects for testing was repeated one hundred times to obtain robust estimations of model performances At each repetition, 5-fold cross-validation was carried out to select the best model over the training subset. Best results were achieved by a bidirectional long short-term memory (BLSTM), obtaining an accuracy of 0.83 and AUC of 0.73 with good sensitivity and specificity values.

Does a Concise Patient-reported Outcome Measure Provide a Valid Measure of Physical Function for Cancer Patients After Lower Extremity Surgery?

Current functional assessment tools for orthopaedic oncology are long surveys that contribute to patients' survey fatigue and yet lack the ability to discern meaningful differences in a patient population that is often mobile but unable to perform strenuous activities. We sought to determine whether a shorter, novel tool based on existing, validated surveys could better capture differences in a sample of orthopaedic oncology patients. (1) Can a concise fixed-item functional tool derived from the 50 items in the Toronto Extremity Salvage Score for the lower extremity (TESS LE) and the Lower Extremity Functional Scale (LEFS) demonstrate similar responsiveness in terms of sensitivity and specificity? (2) What is the precision and accuracy of the concise tool compared with the TESS LE and LEFS? Functional outcome data were collected and maintained in a longitudinally maintained database at a single institution. Patients were included in the study if (1) they had undergone a tumor excision or a nononcologic orthopaedic procedure (for example, arthroplasty for osteoarthritis) for a bone or soft tissue tumor affecting lower extremity function, and (2) they had completed the LEFS, TESS LE, and Patient-Reported Outcomes Measurement Information System (PROMIS) global health tool on at least two clinic visits. Between September 2014 and April 2022, we treated 14,234 patients for primary bone or soft tissue sarcoma, metastatic disease to bone, or orthopaedic sequelae of chronic cancer care. Approximately 6% (854 of 14,234) were excluded due to the need of a language translator. Approximately 2% (278 of 13,380) refused or were unable to participate. Seventy-two percent (9433 of 13,102) of the patients had an operation on a lower extremity. Of these, 4% (339 of 9433) of the patients completed the TESS LE, LEFS, and Item 3 of the PROMIS global health tool on ≥ 2 clinic visits. Of the patients in the current study, 49% (167 of 339) were women, and 27% (93 of 339) had metastatic carcinoma. Twelve percent (41 of 339) of the patients died before the end of the study period. Spearman rank-order correlation, principal component analysis (PCA), and item response theory (IRT) modeling identified 14 highly discriminating items from the TESS LE and LEFS. Multiple linear stepwise regression (MLSR) was performed with the dependent variable being the summary score of the 14 items derived from the TESS LE and LEFS and standardized to a percentage of 100. The beta coefficient from the MLSR was used to derive a weight for each of the 14 items. Evaluation of the model with 10 to 17 variables was performed to ensure that the model with the 14 items met the most criteria for fit with the PCA, the receiver operating characteristic (ROC) curve, and the IRT modeling criteria. The responsiveness (sensitivity and specificity) of the change scores in the shortened 14-item survey, the 30-item TESS LE, and the 20-item LEFS as compared with the dichotomized changes in Item 3 of the PROMIS global health tool was evaluated using ROCs. The concordance (accuracy and precision) of the 14 items derived from the LEFS and TESS LE was evaluated. The responsiveness (sensitivity and specificity) of the shortened 14-item survey, the TESS LE, and the LEFS to the criterion target of the PROMIS global health tool (Item 3) was similar, with areas under the curve (AUCs) ranging from 0.62 to 0.65 for the ROC curves. The responsiveness of the 14-item survey to the TESS LE showed sensitivity of 96% and specificity of 90%, with an AUC of 0.98 (p < 0.001). The responsiveness of the 14 items to the LEFS showed sensitivity of 95% and specificity of 86%, with an AUC of 0.96. The validity of the 14 items to the TESS LE was measured by concordance, with a precision of 0.98 and an accuracy of 0.97. Concordance of the 14 items to the LEFS showed a precision of 0.98 and accuracy of 0.83. The concise 14 items derived from patient-reported responses in the TESS LE and LEFS outcome measures showed similar responsiveness (sensitivity and specificity) as the original TESS LE and LEFS for cancer patients after lower extremity orthopaedic surgery performed for oncologic and nononcologic indications. The concise 14 items have a similar ability to the TESS LE and LEFS to tell the clinician or patient how they are functioning compared with other patients. These 14 items are shorter than the combined 50 items of the TESS LE and LEFS while retaining the capacity to describe a broad range of lower extremity function for orthopaedic oncology patients. We have named the 14-item survey the Lower Extremity Oncology Functional Assessment Tool.Level of Evidence Level II, diagnostic study.

Tidal Breathing Analysis as a Prognostic Index for Airway Obstruction Trajectory and Asthma in Preterm Infants.

An easy-to-implement and accurate lung function assessment tool for preterm infants is crucial to manage lifelong respiratory morbidities. We aimed to determine which pulmonary function parameters in preterm infants can predict the trajectory of airway obstruction and asthma development after 4years of age. We evaluated 52 preterm infants who had undergone both tidal breathing flow-volume loop (TBFVL) and multiple-breath washout (MBW) analyses in infancy and spirometry after the age of 4years. We evaluated the association between pulmonary function parameters in infancy and childhood and the pulmonary function trajectory until 13years of age and compared the changes in this trajectory according to pulmonary function parameters in infancy. Time to peak expiratory flow/expiratory time (TPEF/TE) in infancy was associated with FEV1, FEF25-75, and dysanapsis ratio in childhood and differed according to level of airway obstruction assessed by FEV1, FEV1/FVC, and FEF25-75, an asthma development. TPEF/TE was a significant predictive factor for airway obstruction and asthma after 4years of age, after adjusting for sex, extreme prematurity, duration of supplementary oxygen and mechanical ventilation, and recurrent wheezing during infancy. In premature infants with lower TPEF/TE, subsequent pulmonary function parameters remained low until 13years of age. In preterm infants, TPEF/TE could be useful to predict airway obstruction and asthma after 4years of age and even a lower pulmonary function trajectory until 13years of age. This information may help clinicians to provide lifelong care for pulmonary morbidity in children and adolescents born preterm.

Optimizing individualized therapy decision-making in multiple myeloma (MM): integration and impact of the Revised Myeloma Comorbidity Index in the MM-tumor board

AbstractMultiple Myeloma (MM) is a hematological disease predominantly affecting elderly patients. The complexity of current treatment necessitates individualized approaches. Therein, functional assessment (FA) tools, such as the Revised Comorbidity Index (R-MCI) at our University- and Comprehensive Cancer Center Freiburg, play a crucial role. This study aimed to determine (a) the implementation of the R-MCI in our MM-tumor board (MM-TB), (b) its impact on treatment guidance at baseline and (c) potential changes during follow-up. This exploratory study investigated R-MCI coverage and distribution in a cohort of patients with multiple TB presentations. Among them, a follow-up patient cohort undergoing subsequent MM-therapy was analyzed to determine treatment adjustments and changes in patients’ condition measured by R-MCI alterations. During our 3-year assessment period, 565 patients were presented in our MM-TB, totaling 1256 TB-presentations. In the multiple TB presentation cohort, the median number of TB presentations was 3 (range: 2–12). R-MCI scores within the MM-TB were available in 94%, whereas in 6%, the R-MCI had not been integrated. Among these, potential failure to identify the need for treatment modifications was determined. In the follow-up cohort, patient characteristics were typical for referral/university centers. Dose reductions were performed in 55% and were more prevalent among patients with ≥ 4 vs. lesser TB presentations. Most patients (55%) showed a fitness stabilization or improvement via follow-up R-MCI. R-MCI integration in MM-TB exceeded &gt; 90%, indicating its successful integration for treatment support. Our results underscore its value in guiding therapy decisions, providing a comprehensive assessment beyond age considerations.

Diagnostic accuracy of hemodynamic assessment of intracranial atherosclerotic stenosis from a single angiographic view: a validation study

BackgroundThe aim of this study is to assess the feasibility of identifying the hemodynamic status of intracranial atherosclerotic stenosis (ICAS) using angio-based fractional flow (FF) calculated from a single angiographic...

Internal Consistency and Floor/Ceiling Effects of the Gross Motor Function Measure for Use with Children Affected by Cancer: A Cross-Sectional Study.

Children/adolescents with cancer can develop adverse effects impacting gross motor function. There is a lack of gross motor function assessment tools that have been validated for this population. The aim of this multicenter cross-sectional study was to preliminary validate the 88-item Gross Motor Function Measure (GMFM-88) for use in children/adolescents with cancer, exploring internal consistency and floor/ceiling effect. Inclusion criteria regarded children/adolescents diagnosed with cancer on treatment or <1 year off therapy. The internal consistency was assessed using Cronbach's α, and the floor-ceiling effects were calculated through percentage. This study involved 217 participants with heterogeneous neoplasm conditions. Internal consistency was good, with a Cronbach's α of 0.989. Floor-ceiling effect analysis reveals that several items obtained a dichotomous scoring distribution in each of the five sub-scales of the GMFM-88. This can be explained by the heterogeneous clinical characteristics of the target population. The preliminary validation of GMFM-88 in a group of children/adolescents affected by cancer suggests that some items are not able to discriminate between different gross motor function levels, and therefore it does not represent an informative tool to measure gross motor function in children with cancer. Future research is needed to define which ones could be more useful for clinical practice.

Virus-like particles as robust tools for functional assessment: Deciphering the pathogenicity of ABCA4 genetic variants of uncertain significance

The retina-specific ABCA transporter, ABCA4, is essential for vision, and its genetic variants are associated with a wide range of inherited retinal degenerative diseases (IRDs) leading to blindness. Of the 1,630 identified missense variants in ABCA4, ∼50% are of unknown pathogenicity (variants of unknown significance, VUS). This genetic uncertainty presents three main challenges: (i) inability to predict disease-causing variants in relatives of IRD patients with multiple ABCA4 mutations; (ii) limitations in developing variant-specific treatments; and (iii) difficulty in using these variants for future disease prediction, affecting patients' life-planning and clinical trial participation. To unravel the clinical significance of ABCA4 genetic variants at the level of protein function, we have developed a virus-like particle (VLP)-based system that expresses the ABCA4 protein and its variants. We validated the efficacy of this system in the enzymatic characterization (ATPase activity) of VLPs harboring ABCA4 and two variants of established pathogenicity: p.N965S and p.C1488R. Our results were consistent with previous reports and clinical phenotypes. We also applied this platform to characterize the VUS p.Y1779F and observed a functional impairment, suggesting a potential pathogenic impact. This approach offers an efficient, high-throughput method for ABCA4 VUS characterization. Our research points to the significant promise of the VLP-based system in the functional analysis of membrane proteins, offering important perspectives on the disease-causing potential of genetic variants and shedding light on genetic conditions involving such proteins.

Location-based differences in cognition and functional capacity: Consistent levels of impairment in participants with schizophrenia compared to healthy controls

Cognitive performance manifests regional differences, correlated with education. There is less information available about regional differences in performance-based measures of functional capacity. In multi-national trials focused on cognitive enhancement, it may be impossible to validate every measure in all locations. It is unknown if regional differences in healthy controls’ (HC) performance affects relative levels of impairment in participants with schizophrenia (SCZ). A multi-site study comparing SCZ and HC administered the MATRICS Consensus Cognitive Battery (MCCB) and Virtual Reality Functional Capacity Assessment Tool (VRFCAT) to 164 HC participants and 164 with SCZ across three sites (Columbia, SC, Miami, and San Diego) and a representative sample of HC (n = 390) completed the VRFCAT in Durham, NC. Performance was compared between HC and SCZ participants at the validation sites. There were statistically significant cross-site differences in HC performance on both the MCCB and VRFCAT. Differences between HC and SCZ on MCCB and VRFCAT were substantial at all three sites, indicating that regional variations in HC performance did not induce reduced differences from SCZ participants. Regional differences were smaller than diagnostic group differences, suggesting that relative impairments of participants with SCZ is consistently preserved across performance differences in HC.

Identification of the most relevant aspects of spinal muscular atrophy (SMA) with impact on the quality of life of SMA patients and their caregivers: the PROfuture project, a qualitative study

BackgroundSMA is a hereditary neuromuscular disease that causes progressive muscle weakness and atrophy. Several studies have shown that the burden of SMA is very high at many levels. Functional assessment tools currently used do not completely address the impact of the disease in patients’ life. The objective of this qualitative study was to identify aspects of SMA that are relevant to patients and to design items useful for assessment purposes.ResultsFive focus group sessions were run during an annual SMA families meeting in Madrid, Spain. Focus groups were composed by parents of SMA type I children, sitter children type II-III, parents of sitter children type II-III, adult patients, and parents of walker children. Two trained facilitators conducted the focus groups using a semi-structured guideline to cover previously agreed topics based on the input of a Scientific and Patient Advisory Committee. The guideline was adapted for the different groups. According to what was communicated by participants, SMA entails a high burden of disease for both patients and their parents. Burden was perceived in physical, psychological, and social areas. Patient’s physical domain was the most relevant for participants, especially for parents of non-ambulant children, followed by limitations of motor scales to capture all changes, parents psychological burden, treatment expectations and patient’s psychological burden. Ten domains were the main areas identified as impacted by the disease: mobility and independence, fatigue and fatigability, infections and hospital consultations, scoliosis and contractures, vulnerability, pain, feeding, time spent in care, breathing, and sleep and rest.ConclusionsThis study confirms the necessity of evaluating other aspects of the disease that are not assessed in the functional motor scale. Measures of other aspects of the disease, such as pain, fatigue, feeding, should be also considered. A patient-reported outcomes instrument measuring such aspects in a valid and reliable way would be very useful. This study generated a list of new items relevant to be systematically measured in the assessment of the impact of SMA on the patients’ everyday life.

A Pain in the Pilot.

Multi-agency guidelines recommend use of a functional pain assessment tool as an objective assessment of pain, rather than relying on a subjective verbal rating scale. This project was created to address issues managing Patients' pain in inpatient settings. The project aimed to answer: 'How can we adopt the use of a Functional Pain Assessment into our clinical practice, optimising its effectiveness for ALL patient groups in our inpatient ward areas?' Output from multi-disciplinary working group: two electronic documents were created - Pain Assessment Tool and Pain Observations Chart: for staff to document routine pain observations. Five wards participated in the pilot study, with training/support provided. Result: Staff and patients preferred the new approach, compared to previous pain documentation method. However, documentation compliance was not as good as expected. Pilot proved the concept, documents are effective in pain management, but more education and support is needed to embed cultural shift.

Prognostic impact of quantitative flow ratio (QFR)-consistent complete revascularization in patients with myocardial infarction and multivessel coronary artery disease

Complete revascularization is associated with improved outcomes in patients with myocardial infarction and multivessel coronary artery disease. Quantitative flow ratio (QFR) represents an emerging angiography-based tool for functional lesion assessment. The present study investigated the prognostic impact of QFR-consistent complete revascularization in patients with myocardial infarction and multivessel disease. A total of 792 patients with myocardial infarction and multivessel disease were enrolled in the analysis. Post-hoc QFR analyses of 1,320 nonculprit vessels were performed by investigators blinded to clinical outcomes. The primary endpoint was a composite of all-cause death, nonculprit vessel related nonfatal myocardial infarction, and ischemia-driven revascularization at 2 years after index myocardial infarction. Patients were stratified into a QFR-consistent PCI group (n = 646) and a QFR-inconsistent PCI group (n = 146), based on whether the intervention was congruent with the QFR-determined functional significance of the nonculprit lesions. The primary endpoint occurred in a total of 22 patients (3.4%) in the QFR-consistent PCI group and in 27 patients (18.5%) in the QFR-inconsistent group (HR 0.17, 95% CI 0.10-0.30, P < .001).The difference in the primary endpoint was driven by reduced rates of nonfatal myocardial infarction (2.0% vs. 15.1%; HR 0.13, 95% CI 0.06-0.25; P < .001) and ischemia-driven revascularization (1.2% vs. 5.5%; HR 0.21, 95% CI 0.08-0.57; P = .001) in the QFR-consistent PCI group. Among patients with myocardial infarction and multivessel disease, a QFR-consistent complete revascularization was associated with a reduced risk of all-cause mortality, nonfatal myocardial infarction, and ischemia-driven revascularization. These findings underline the value of angiography-based functional lesion assessment for personalized revascularization strategies.

Association of combined low physical activity and low dietary diversity with mild cognitive impairment among community-dwelling Japanese older adults.

This study aimed to investigate the potential association between the combination of low physical activity and low dietary diversity with mild cognitive impairment (MCI) in older Japanese adults. Data from 600 older adults (mean age 74.1 ± 6.4 years; 62.0% women) were analyzed. We evaluated dietary variety based on the Food Frequency Score (FFS) (maximum 30 points) by assessing the one-week consumption frequencies of ten foods. An FFS of ≤ 16 indicated low dietary diversity. We assessed MCI using the National Center for Geriatrics and Gerontology (NCGG) Functional Assessment Tool. Physical activity levels was determined based on participant responses to two questions: "Do you engage in moderate levels of physical exercise or sports aimed at health?" and "Do you engage in low levels of physical exercise aimed at health?". Participants who responded "No" to both questions were classified as having low physical activity levels. We classified the participants into robust, low-dietary diversity, low-physical activity, and coexistence groups. The overall prevalence of MCI was 20.7%, with rates in the robust, low dietary diversity, low physical activity, and coexistence groups of 17.7%, 24.7%, 25.0%, and 41.9%, respectively. Multiple logistic regression analysis revealed that low dietary diversity and physical activity were associated with MCI in older adults (odds ratio [OR] 2.80, 95% confidence interval [CI] 1.22-6.28). The results of the present study demonstrated the association of the co-occurrence of low dietary diversity and low physical activity with MCI. Older adults with both risk factors may require early detection, as well as physical activity and dietary interventions.

Enzyme replacement therapy and immunotherapy lead to significant functional improvement in two children with Pompe disease: a case report

BackgroundPompe disease, a rare autosomal recessive disorder caused by acid alpha-glucosidase deficiency, results in progressive glycogen accumulation and multisystem dysfunction. Enzyme replacement therapy with recombinant human acid alpha-glucosidase is the standard of care; however, some patients develop anti-recombinant human acid alpha-glucosidase antibodies, leading to reduced efficacy. This case report presents two infants with early-onset Pompe disease who developed IgG antibodies to enzyme replacement therapy and were subsequently treated with methotrexate, highlighting the importance of monitoring antibody development and exploring alternative therapeutic approaches.Case presentationPatient 1, a 10-month-old female from Bogota, Colombia, presented with generalized hypotonia, macroglossia, hyporeflexia, and mild left ventricular hypertrophy. Diagnostic tests confirmed early-onset Pompe disease, and enzyme replacement therapy was started at 12 months. Due to a lack of improvement and high anti-recombinant human acid alpha-glucosidase IgG antibody titers (1:1800), methotrexate was started at 18 months. After 8 months of combined therapy, antibody titers were negative and significant improvement in motor function was observed using the Gross Motor Function Measure 88. Patient 2, a 7-year-old female from Bogota, Colombia, was diagnosed with early-onset Pompe disease at 12 months and initiated enzyme replacement therapy. At 5 years of age, she experienced frequent falls and grip strength alterations. Functional tests revealed motor development delay, generalized hypotonia, and positive anti-recombinant human acid alpha-glucosidase IgG antibody titers (6400). Methotrexate was initiated, leading to a reduction in falls and antibody titers (3200) after 6 months, with no adverse events or complications. Motor function improvement was assessed using the Motor Function Measurement 32.ConclusionsThe presented cases highlight the importance of monitoring patients for anti-recombinant human acid alpha-glucosidase antibody development during enzyme replacement therapy and the potential benefit of methotrexate as an immunomodulatory agent in early-onset Pompe disease. Early diagnosis and timely initiation of enzyme replacement therapy, combined with prophylactic immune tolerance induction, may improve clinical outcomes and reduce the development of anti-recombinant human acid alpha-glucosidase antibodies. The cases also highlight the importance of objective motor function assessment tools, such as Gross Motor Function Measure 88 and Motor Function Measurement 32, in assessing treatment response. Further research is needed to optimize treatment regimens, monitor long-term effects, and address the current limitations of enzyme replacement therapy in Pompe disease.

T4 - Evaluation of a Functional Assessment Tool for Alcohol Use

T4 - Evaluation of a Functional Assessment Tool for Alcohol Use

Exploring Kainic Acid-Induced Alterations in Circular Tripartite Networks with Advanced Analysis Tools.

Brain activity implies the orchestrated functioning of interconnected brain regions. Typical in vitro models aim to mimic the brain using single human pluripotent stem cell-derived neuronal networks. However, the field is constantly evolving to model brain functions more accurately through the use of new paradigms, e.g., brain-on-a-chip models with compartmentalized structures and integrated sensors. These methods create novel data requiring more complex analysis approaches. The previously introduced circular tripartite network concept models the connectivity between spatially diverse neuronal structures. The model consists of a microfluidic device allowing axonal connectivity between separated neuronal networks with an embedded microelectrode array to record both local and global electrophysiological activity patterns in the closed circuitry. The existing tools are suboptimal for the analysis of the data produced with this model. Here, we introduce advanced tools for synchronization and functional connectivity assessment. We used our custom-designed analysis to assess the interrelations between the kainic acid (KA)-exposed proximal compartment and its nonexposed distal neighbors before and after KA. Novel multilevel circuitry bursting patterns were detected and analyzed in parallel with the inter- and intracompartmental functional connectivity. The effect of KA on the proximal compartment was captured, and the spread of this effect to the nonexposed distal compartments was revealed. KA induced divergent changes in bursting behaviors, which may be explained by distinct baseline activity and varied intra- and intercompartmental connectivity strengths. The circular tripartite network concept combined with our developed analysis advances importantly both face and construct validity in modeling human epilepsy in vitro.

Quantitative flow ratio for the functional assessment of extracranial internal carotid artery stenosis.

In asymptomatic patients presenting with significant internal carotid artery (ICA) stenoses undergoing endovascular revascularization, a selective angiography before stenting (CAS) is required. Sometimes, angiographic findings could be discordant from non-invasive assessment and a tool able to evaluate functional relevance of the stenosis could be of value. We sought to evaluate the usefulness of quantitative flow ratio (QFR) as angiography-based tool for functional assessment of ICA stenoses. We prospectively enrolled 50 asymptomatic patients undergoing CAS. Peak systolic velocity (PSV, cm/s) assessed at color Doppler echocardiography was used to identify significant stenoses (PSV >125 cm/s). At angiography, assessment of ICA stenosis was obtained visually (%DS<inf>VISUAL</inf>) and according NASCET criteria (%DS<inf>NASCET</inf>). Stenoses were considered significant if >60%. After exclusion of 20 vessels, QFR, area stenosis (AS, %) and minimal lumen area (MLA, mm2) were obtained in the remaining 80 vessels. At linear regression analysis, QFR significantly correlated with PSV (r2=0.52, P<0.001) as well as with %DS<inf>NASCET</inf> (r2=0.68, P<0.001) and %DS<inf>VISUAL</inf> (r2=0.71, P<0.001). Using PSV as reference, QFR showed good accuracy to predict functionally significant stenosis (AUC=0.98, P<0.001) with a cut-off value of 0.93. As compared with %DS<inf>NASCET</inf> and %DS<inf>VISUAL</inf>, QFR showed a significantly higher accuracy (61% vs. 73% vs. 94%, respectively; P<0.05), sensitivity (43% vs. 61% vs. 93%, respectively; P<0.05) and negative predictive value (46% vs. 51% vs. 85%, respectively; P<0.05) for detecting hemodynamically significant ICA stenoses. This study suggest the potential benefit of adopting QFR for functional assessment of extracranial ICA stenoses. These data should be validated in larger studies.

Skilled reaching test for shoulder function assessment in a rat model of rotator cuff tear: a pilot study

BackgroundFunctional assessments are crucial to evaluate treatment outcomes in clinical and animal studies on rotator cuff injuries. While gait analysis is commonly used to assess animal models of rotator cuff tears, it is less relevant for human patients as the human shoulder is typically assessed in a non-weight-bearing condition. The present study introduces the skilled reaching test as a shoulder functional assessment tool for rats, which allows for evaluation without weight bearing.MethodsIn the control group, 8 male Sprague–Dawley rats received rotator cuff tear surgery without repair. In the rotator cuff repair group, 20 rats received rotator cuff repair at 4 weeks post rotator cuff tear. For the skilled reaching test, rats were trained to extend their forelimbs to fetch food pellets, and the number of trials, number of attempts and the success rate were recorded. The gait analysis and skilled reaching test were performed at baseline, 4 weeks post-tear, 1, 2, 4, and 8 weeks post-repair. The repeated measures analysis of variance was used to evaluate the effects of time on the shoulder function. The significance level was set at 0.05.ResultsThe skilled reaching test required 216 h to conduct, while the gait analysis took 44 h. In the rotator cuff repair group, gait performance significantly deteriorated at 1 week post-repair and restored to 4 weeks post-tear levels at 4 weeks post-repair. Regarding the skilled reaching test, the number of attempts, number of trials and the success rate decreased at 1 week post-repair. Subsequently, there was a brief rebound in performance observed at 2 weeks post-repair, followed by a continued decline in the number of attempts and trials. By 8 weeks post-repair, only the success rate had restored to levels similar to those observed at 4 weeks post-tear.ConclusionThe skilled reaching test can detect functional deficiencies following rotator cuff tear and repair, while it requires high time and labour costs.