Comprehensive Functional Assessment Research Articles

The correlation of gait and muscle activation characteristics with locomotion dysfunction grade in elderly individuals

ObjectiveTo investigate the differences and regularity of gait and muscle activation characteristics parameters in the Locomotion Dysfunction Grade (LDG) scale assessment in elderly individuals, and analyse the correlation between objective parameters and scale grading. Thus, to propose a novel detection mode for elderly individuals, which combined the LDG scale with objective detection. It can not only provide quantitative data for intelligent evaluation and rehabilitation, but also provided more accurate reference for the classification of care levels in elderly care policies.MethodsElderly individuals (n = 159) who underwent gait analysis and sEMG at the Chinese Rehabilitation Research Center from January 2019 to September 2023 were included. According to the LDG scale, the elderly individuals were divided into four groups, namely, the LDG4, LDG5, LDG6 groups and the healthy control group. Four indicators, namely, spatiotemporal, kinematic, dynamic gait parameters and muscle activation characteristics data, were collected. Changes in these characteristics of elderly individuals with lower extremity motor dysfunction were evaluated and analysed statistically.ResultsThe spatiotemporal gait parameters were significantly lower in the LDG4, LDG5, LDG6 groups than in the healthy control group. The double support phase was positively correlated with the LDG, while the swing phase, step length and velocity were negatively correlated (P < 0.05). The movement angles of both hips, knees and ankles were significantly limited and negatively correlated with the LDG (P < 0.05). Compared with those in the healthy control group, the centre of pressure (COP) path length were greater, and the average COP velocity was significantly lower (P < 0.05) in the LDG4, LDG5, LDG6 groups. The regularity of muscle activation clearly changed. The root mean square of the gastrocnemius medialis was positively correlated with LDG (P < 0.05), while the tibialis anterior showed no regularity.ConclusionAs the LDG increased, the differences in spatiotemporal, kinematic and dynamic gait parameters between elderly individuals with motor dysfunction and the healthy individuals gradually increased. The muscle activation characteristics parameters showed an abnormal activation pattern. These parameters were correlated with the LDG, providing a more comprehensive and objective assessment of lower extremity motor function in elderly individuals, improve assessment accuracy, and help accurate rehabilitation.

Impaired Visual Function in Posterior Vitreous Detachment Assessed With the Active-Learning Quantitative Contrast Sensitivity Function Test

Introduction: To investigate whether there is visual function impairment in patients with posterior vitreous detachment (PVD) using the active-learning quantitative contrast sensitivity function test. Methods: In this cross-sectional study, contrast sensitivity was measured in eyes with PVD and eyes without PVD using the quantitative contrast sensitivity function algorithm on the Adaptive Sensory Technology platform. Outcomes included the area under the log contrast sensitivity function curve, contrast acuity, and contrast sensitivity thresholds at 1 to 18 cycles per degree (cpd). Snellen visual acuity (VA) was also measured. Mixed-effects multiple linear regression analyses were performed to evaluate the association between the presence of PVD and visual function, controlling for age and lens status. Results: The cohort comprised 232 healthy eyes of 205 participants; of these, 80 eyes of 69 patients had PVD. There was no significant association between VA and PVD presence. However, PVD was significantly associated with decreased contrast sensitivity thresholds at 1.5 cpd (β, −0.058; P = .003) and 3 cpd (β, −0.067; P = .004). Contrast sensitivity thresholds at lower (1 cpd) or higher (6, 12, 18 cpd) spatial frequencies did not significantly correlate with PVD presence. Even in the subgroup of symptomatic PVD eyes, VA was not significantly decreased, while quantitative contrast sensitivity function outcomes showed visual function deficits at low spatial frequencies (1.5 cpd and 3 cpd). Conclusions: Contrast sensitivity measured with the quantitative contrast sensitivity function test showed visual function deficits in eyes with PVD that would have been missed with VA testing alone. Incorporating this test in the retina clinic might offer a more comprehensive functional assessment of eyes with PVD, serving as an adjunct outcome metric in clinical decision-making.

Comprehensive appraisal of lung function in young COPD patients: a single center observational study

PurposeThe present study aimed to investigate the clinical characteristics and lung function impairment in young people diagnosed with chronic obstructive pulmonary disease (COPD).Patients and methodsWe retrospectively enrolled patients with COPD who underwent symptom assessment and comprehensive pulmonary function tests at the First Affiliated Hospital of Guangzhou Medical University between August 2017 and March 2022. The patients were categorized into two groups based on age: a young COPD group (aged 20–50 years) and an old COPD group (aged > 50 years).ResultsA total of 1282 patients with COPD were included in the study, with 76 young COPD patients and 1206 old COPD patients. Young COPD patients exhibited a higher likelihood of being asymptomatic, lower rates of smoking, and a lower smoking index compared to old COPD patients. Although young COPD patients had higher median post-bronchodilator forced expiratory volume in 1 s (post-BD FEV1) (1.4 vs.1.2 L, P = 0.019), diffusing capacity of the lung for carbon monoxide (DLCO) (7.2 vs. 4.6, P<0.001), and a lower median residual volume to total lung capacity ratio (RV/TLC) compared to their older counterparts, there were no differences observed in severity distribution by GOLD categories or the proportion of lung hyperinflation (RV/TLC%pred > 120%) between two groups. Surprisingly, the prevalence of reduced DLCO was found to be 71.1% in young COPD, although lower than in old COPD (85.2%).ConclusionYoung COPD showed fewer respiratory symptoms, yet displayed a similar severity distribution by GOLD categories. Furthermore, a majority of them demonstrated lung hyperinflation and reduced DLCO. These results underscore the importance of a comprehensive assessment of lung function in young COPD patients.

An Intelligent Hand-Assisted Diagnosis System Based on Information Fusion.

This research proposes an innovative, intelligent hand-assisted diagnostic system aiming to achieve a comprehensive assessment of hand function through information fusion technology. Based on the single-vision algorithm we designed, the system can perceive and analyze the morphology and motion posture of the patient's hands in real time. This visual perception can provide an objective data foundation and capture the continuous changes in the patient's hand movement, thereby providing more detailed information for the assessment and providing a scientific basis for subsequent treatment plans. By introducing medical knowledge graph technology, the system integrates and analyzes medical knowledge information and combines it with a voice question-answering system, allowing patients to communicate and obtain information effectively even with limited hand function. Voice question-answering, as a subjective and convenient interaction method, greatly improves the interactivity and communication efficiency between patients and the system. In conclusion, this system holds immense potential as a highly efficient and accurate hand-assisted assessment tool, delivering enhanced diagnostic services and rehabilitation support for patients.

Klotho enhances diastolic function in aged hearts through Sirt1-mediated pathways.

Aging leads to a progressive decline in cardiac function, increasing the risk of heart failure with preserved ejection fraction (HFpEF). This study elucidates the impact of α-Klotho, an anti-aging hormone, on cardiac diastolic dysfunction and explore its downstream mechanisms. Aged wild-type and heterozygous Klotho-deficient mice received daily injection of soluble α-Klotho (sKL) for 10weeks, followed by a comprehensive assessment of heart function by echocardiography, intracardiac pressure catheter, exercise tolerance, and cardiac pathology. Our findings show that klotho deficiency accentuated cardiac hypertrophy, diastolic dysfunction, and exercise intolerance, while sKL treatment ameliorates these abnormalities and improves cardiac capillary densities. Downstream of klotho, we focused on the Sirtuin1 (Sirt1) signaling pathway to elucidate the potential underlying mechanism by which Klotho improves diastolic function. We found that decreased Klotho levels were linked with Sirt1 deficiency, whereas sKL treatment restored Sirt1 expression in aged hearts and mitigated the DNA damage response pathway activation. Through tandem mass tag proteomics and unbiased acetylomics analysis, we identified 220 significantly hyperacetylated lysine sites in critical cardiac proteins of aged hearts. We found that sKL supplementation attenuated age-dependent DNA damage and cardiac diastolic dysfunction. In contrast, Klotho deficiency significantly increased hyperacetylation of several crucial cardiac contractile proteins, potentially impairing ventricular relaxation and diastolic function, thus predisposing to HFpEF. These results suggest the potential benefit of sKL supplementation as a promising therapeutic strategy for combating HFpEF in aging.

Klotho enhances diastolic function in aged hearts through Sirt1-mediated pathways.

Aging leads to a progressive decline in cardiac function, increasing the risk of heart failure with preserved ejection fraction (HFpEF). This study elucidates the impact of α-Klotho, an anti-aging hormone, on cardiac diastolic dysfunction and explore its downstream mechanisms. Aged wild-type and heterozygous Klotho-deficient mice received daily injection of soluble α-Klotho (sKL) for 10weeks, followed by a comprehensive assessment of heart function by echocardiography, intracardiac pressure catheter, exercise tolerance, and cardiac pathology. Our findings show that klotho deficiency accentuated cardiac hypertrophy, diastolic dysfunction, and exercise intolerance, while sKL treatment ameliorates these abnormalities and improves cardiac capillary densities. Downstream of klotho, we focused on the Sirtuin1 (Sirt1) signaling pathway to elucidate the potential underlying mechanism by which Klotho improves diastolic function. We found that decreased Klotho levels were linked with Sirt1 deficiency, whereas sKL treatment restored Sirt1 expression in aged hearts and mitigated the DNA damage response pathway activation. Through tandem mass tag proteomics and unbiased acetylomics analysis, we identified 220 significantly hyperacetylated lysine sites in critical cardiac proteins of aged hearts. We found that sKL supplementation attenuated age-dependent DNA damage and cardiac diastolic dysfunction. In contrast, Klotho deficiency significantly increased hyperacetylation of several crucial cardiac contractile proteins, potentially impairing ventricular relaxation and diastolic function, thus predisposing to HFpEF. These results suggest the potential benefit of sKL supplementation as a promising therapeutic strategy for combating HFpEF in aging.

P-582 Analysis of assisted reproductive outcomes for gynecologic cancer survivors: a retrospective study

Abstract Study question Do women diagnosed with gynecologic cancer have worse pregnancy and neonatal outcomes of assisted reproductive technology (ART) ? Summary answer Decreased live birth rate was observed in female gynecologic cancer patients undergoing ART, particularly in endometrial cancers and cervical cancers. What is known already Gynecologic malignancies comprise approximately 13% of female cancer diagnoses, and oncological treatments such as surgery, chemotherapy, abdominal or pelvic radiotherapy, and hormonotherapy may induce infertility, premature ovarian failure, or early menopause, resulting in a loss of reproductive potential. ART has emerged as an important option for cancer patients undergoing treatment, but the reproductive outcomes of ART among cancer survivors remain poorly understood. Limited research exists regarding the impact of a history of gynecologic cancer on reproductive outcomes of ART. Study design, size, duration 136 women diagnosed with gynecologic cancer who underwent their first IVF/ICSI treatment between 2013 and 2021 were retrospectively enrolled in this study. 241 infertile women without any history of cancer were matched to the cancer group. Participants/materials, setting, methods Women diagnosed with gynecologic cancer who underwent their first IVF/ICSI treatment between 2013 and 2021 were included. Infertile women without any history of cancer were matched to the cancer group. The primary outcome was the cumulative live birth rate. A propensity score-based patient-matching approach was adopted to ensure comparability between individuals with and without specific cancer type. Main results and the role of chance A total of 136 patients with a history of gynecologic cancer and 241 healthy infertile controls were included in this study. Endometrial cancer constituted 50.70% of the cases and cervical cancer constituted 34.60% of the cases. The cancer group exhibited significant shorter duration of stimulation, lower levels of estradiol, lower number of retrieved oocytes, day-3 embryos, and blastocysts compared to the control group (P &amp;lt; 0.05). The cumulative live birth rate of the gynecologic cancer group was significantly lower than that of the control group (36.10% vs. 60.50%, P &amp;lt; 0.001). Maternal and neonatal complications did not significantly differ between the groups (P &amp;gt; 0.05). The endometrial cancer and cervical cancer groups showed significantly lower cumulative live birth rates than their matched controls (38.60% vs. 64.50%, P = 0.011 and 24.20% vs. 68.60%, P &amp;lt; 0.001, respectively). Limitations, reasons for caution Our study was limited by the retrospective design in nature and small sample size of its patient cohort. In addition, the effect of cancer treatments was not evaluated specifically in the current study due to the limited number of patients and possible inconsistency in surgical operations. Wider implications of the findings Our study provides data support for further exploration of the effects of endometrial cancer, cervical cancer, and other gynecologic cancers on fertility. Comprehensive ovarian function assessment, detailed counseling, individualized fertility guidance, and close follow-up after ART therapy are recommended for patients with gynecologic malignancy history. Trial registration number Not applicable

Effect of Intermittent Theta Burst Stimulation Dual-Target Stimulation on Lower Limb Function in Patients with Incomplete Spinal Cord Injury: A Randomized, Single-Blind, Sham-Controlled Study

To explore the influence of intermittent theta burst stimulation (iTBS) dual-target stimulation on lower limb function in patients with incomplete spinal cord injury (iSCI). A randomized, single -blind,sham-controlled trial was used in this study. Thirty iSCI patients with lower limb dysfunction meeting the inclusion criteria were randomly divided into a sham group and an iTBS group, with 15 cases in each group. The iTBS group received conventional rehabilitation therapy combined with iTBS dual-target stimulation on the central cerebral sulcus and the nerve root of the spinal cord injury segment. The sham group was treated with conventional rehabilitation therapy combined with iTBS dual-target sham stimulation therapy. Comprehensive functional assessment was performed on all patients before treatment, on the Day 3 and Day 21 of treatment.The main evaluation indicators were as follows: amplitude and latency of motor-evoked potential (MEP) in the anterior tibial muscles of both lower limbs,latency of sensory-evoked potential (SEP) of both lower limbs, knee flexor strength and knee extensor strength, lower extremity motor score (LEMS), lower extremity sensory score (LESS), spinal cord independence measure (SCIM) score and gait parameters (stride speed, stride frequency, stride length, ground reaction force). On day 21 of treatment, in the iTBS group, the MEP amplitude of the anterior tibial muscles increased, the latency of MEP shortened, knee flexor strength and knee extensor strength increased, and the lower extremity motor score and SCIM score of both lower limbs increased. In addition, there were statistically significant differences in the muscle strength of the knee flexion muscle, knee extensor muscle, MEP amplitude, LEMS and SCIM between the two groups (p<0.05). Among the 10 patients who could walk with an assisted walker, the step length and step frequency of the iTBS group were increased compared with the sham group after treatment (p<0.01), and the ground reaction force (GRF) was increased (p<0.05). There was no significant difference in the LESS of the lower limbs between the two groups (p > 0.05). ITBS dual-target stimulation can significantly improve the motor function of both lower limbs in patients with iSCI but does not significantly improve the sensory function of both lower limbs. Therefore, this treatment mode may participate in the reconstruction and repair of some nerve circuits in patients with iSCI. In addition, iTBS dual-target stimulation can improve the ability of iSCI patients to perform daily living.

A comprehensive functional performance assessment battery development and validation among football players

BackgroundSkill and health-related components are required for the assessment of football players’ functional performance, and there is a lack of literature available to measure football players’ functional performance. The study mostly focuses on developing and validating the tool for football players between the ages of 18 and 25.MethodsThis study used a research methodology that focused on the development and verification of a scale. The research consisted of two distinct stages, namely tool development and validity testing. Firstly, the expert panel did a comprehensive analysis of the items and domains of the questionnaire. Subsequently, the Delphi approach was used to assess the content validity of the questionnaire. Later on, the evaluation tool was officially named the complete functional performance assessment battery (CFPA) for football players in India.ResultThe CFPA’s newly developed tool has excellent scale-level content validity, which was more than 0.78 for each item in the tool, i.e., 1 (indicated as extremely relevant), the content validity ratio was bigger than 0.49, and each item’s kappa value was found to be 1, which is excellent. Each item’s universal acceptance was found to be 1 for both the item’s quality and content and Aiken’s V index is also greater than 0.81.ConclusionThe CFPA is a valid tool in India that can be used to check the functional performance of football players.

Effects of Intervention Strategies-Based on Positive Psychology on the Emotional Cognition, Mental Health, and Recovery of Speech Function in Speech Disabilities.

Compared with able-bodied people, speech disabilities are more prone to various mental health problems. We aimed to explore the impact of positive psychology-based intervention strategies on emotional cognition, mental health, and recovery of speech function in speech disabilities. In May 2023, 306 cases of speech disabilities were selected from 112 village committees and 129 neighborhood committees in Jingmen City, China. The control group was given routine speech rehabilitation training, and the observation group was given an intervention strategies-based on positive psychology based on the above training. The Symptom Checklist-90 (SCL-90), Chinese Facial Emotion Test (CFET), Comprehensive Function Assessment for Disabled Children (CFADC), and Boston Diagnostic Aphasia Examination (BDAE) were used to evaluate the two groups of patients before and after intervention. After the intervention, the mental state scores (psychotic, obsessive-compulsive symptoms, somatization, paranoia, terror, hostility, anxiety, and depression) of the observation group were lower than those of the control group (P<0.05). The correct emotional scores in the observation group were higher than those in the control group were. However, the remote error scores of the observation group were lower than those of the control group were. The difference was also statistically significant (P<0.05). The cognitive function score, speech function score, and BDAE score (retelling, writing, fluency, and reading comprehension) of the observation group were all higher than those of the control group (P<0.05). The intervention strategies-based on positive psychology could promote the improvement of health problems and speech function in speech disabilities.

Prognostic Value of a 6-Minute Walk Test in Patients With Transthyretin Cardiac Amyloidosis

BackgroundThe 6-minute walk test (6MWT) represents a comprehensive functional assessment that is commonly used in patients with heart failure; however, data are lacking in patients with transthyretin cardiac amyloidosis (ATTR-CA). ObjectivesThis study aimed to assess the prognostic importance of the 6MWT in patients with ATTR-CA. MethodsA retrospective analysis of patients diagnosed with ATTR-CA at the National Amyloidosis Centre who underwent a baseline 6MWT between 2011 and 2023 identified 2,141 patients, of whom 1,118 had follow-up at 1 year. ResultsThe median baseline 6MWT distance was 347 m (Q1-Q3: 250-428 m) and analysis by quartiles demonstrated an increased death rate with each distance reduction (deaths per 100 person-years: 6.3 vs 9.2 vs 13.6 vs 19.0; log-rank P < 0.001). A 6MWT distance of <350 m was associated with a 2.2-fold higher risk of mortality (HR: 2.15; 95% CI: 1.85-2.50; P < 0.001), with a similar increased risk across National Amyloidosis Centre disease stages (P for interaction = 0.761) and genotypes (P for interaction = 0.172). An absolute (reduction of >35 m) and relative worsening (reduction of >5%) of 6MWT at 1 year was associated with an increased risk of mortality (HR: 1.80; 95% CI: 1.51-2.15; P < 0.001 and HR: 1.89; 95% CI: 1.59-2.24; P < 0.001, respectively), which was similar across the aforementioned subgroups. When combined with established measures of disease progression (N-terminal pro–B-type natriuretic peptide progression and outpatient diuretic intensification), each incremental increase in progression markers was associated with an increased death rate (deaths per 100 person-years: 7.6 vs 13.9 vs 22.4 vs 32.9; log-rank P < 0.001). ConclusionsThe baseline 6MWT distance can refine risk stratification beyond traditional prognosticators. A worsening 6MWT distance can stratify disease progression and, when combined with established markers, identifies patients at the highest risk of mortality.

Comprehensive assessment of memory function, inhibitory control, neural activity, and cortisol levels in late pregnancy.

A considerable proportion of women subjectively perceive a detriment to their cognitive capacity during pregnancy, with decreased memory functions being the most frequently self-reported concerns. However, objective investigation of these perceived cognitive deficits has yielded inconsistent results. This study focused on memory functions during late pregnancy using multiple tasks designed to assess various memory indices, for example, working memory, learning rate, immediate recall, proactive and retroactive interference, delayed recall, retrieval efficiency, visuospatial constructional ability, recognition, and executive function. Additionally, sustained attention and inhibitory control were examined using a combined recognition stop-signal task. Electrophysiological brain activity during this task was recorded using a 128-channel electroencephalographic-event-related potential system. Salivary cortisol levels were assessed both prior to and following the experimental session. In contrast to the widely held belief, results demonstrated that women in late pregnancy did not exhibit a decline in their performance across the various memory tests. In terms of accuracy, there was not a single task in which poorer performance was found for pregnant women. The quality of memory performance was comparable, and in some cases even superior, among women in the pregnancy group. On the stop-signal task, pregnant women exhibited significantly better performance, and their electrophysiological data revealed greater centrally distributed P300 amplitude to "stop" signs, which may signify an enhanced neural efficiency in the domains of inhibitory executive control. Endocrine results revealed that pregnant women exhibited significantly lower levels of salivary cortisol, suggesting an attenuation of hypothalamic-pituitary-adrenocortical axis activity, which may contribute to the optimization of fetal development and growth.

Post-stroke sexual dysfunction in males

IntroductionSexual dysfunction (SD) is a commonly overlooked issue following ischemic stroke (IS), influenced by various risk factors including social, psychological, and biological factors. This study aims to investigate the prevalence and risk factors associated with SD in adult male patients who have experienced an IS. MethodsA descriptive observational cross-sectional study was conducted in Bogotá, Colombia, involving adult male IS patients. Sociodemographic, medical history, pharmacological history, substances consumption, and time since stroke data were collected. Clinical assessments were performed using the NIHSS score, modified Rankin score (mRankin), pain score, and mood evaluation (Beck inventories). The Arizona Sexual Experience (ASEX) scale and the frequency of sexual encounters were used to assess SD. Results50 males included, mean age 63.2 (±9.7) years. The most prevalent medical comorbidities were arterial hypertension (84%) and type 2 diabetes mellitus (DM) (46%). Anxiety or depression were identified in 48%. The mean scores for the NIHSS, mRankin, and pain were 6, 1, and 1, respectively. The average time from IS to clinical assessment was 6.5 months. Sexual dysfunction was observed in 18 (36%) subjects. Age (OR 1.12, 95% CI: 1.02–1.247) and location of the IS in the cortico-subcortical region of the parietal, temporal, or occipital lobes (OR 13.59, 95% CI: 1.58–405.784) were associated with SD. ConclusionSD affects more than one-third of male patients with IS, age, and IS location identified as key risk factors. Comprehensive assessment of sexual function should be incorporated into this patients.

Comprehensive Assessment of Cardiac Function in Breast Cancer Patients: Integrating Multiparametric Speckle Tracking Imaging and Conventional Echocardiography Parameters.

Purpose The purpose of this study is to comprehensively evaluate the role of different echocardiography parameters in breast cancer patients undergoing chemotherapy. While echocardiography examination with calculation of ejection fraction (EF), is pivotal for patient monitoring, its operator dependence and insensitivity to subtle changes in left ventricular (LV) contractility present challenges. Global longitudinal strain (GLS), derived from speckle tracking, is more sensitive and stable than EF. Our research aimed to delineate supplementary echocardiography measurements beneficial for the cardiological monitoring of breast cancer patients. Methods Patients were followed up with echocardiography at baseline, during, and after the chemotherapy. Conventional echocardiography and multiple speckle tracking imaging parameters including myocardial work index, atrial strain, twist, and automatic EF were investigated. Results A total of 25 patients were recruited. A subset (15/25) exhibited pronounced GLS reduction, associated with decreased EF and altered cardiac mechanics. Patients with unchanged GLS were often hypertensive and on specific medications, in particular angiotensin-converting enzyme inhibitors (ACE inhibitors)/angiotensin II receptor blockers (ARBs), potentially indicating protective effects. Despite stability in other parameters, GLS and EF sensitivity highlight their importance. A strong correlation between manual and automated EF measurement methods was also observed. Conclusion Despite the small sample size, across diverse echocardiography parameters, GLS and EF are primarily affected by chemotherapy. Hypertensive individuals exhibited lower susceptibility to chemotherapy-induced damage, likely attributed to the cardioprotective properties of ACE inhibitors and angiotensin II receptor blockers. A strong correlation between automatic and Simpson-based EF was found.

Abstract LB387: Microphysiological modeling of gastric cancer vasculature using iPSC-derived endothelial cells

Abstract Generated induced pluripotent stem cells (iPSCs) from the blood of patients with advanced gastric cancer, differentiating them into endothelial cells and fibroblasts. Utilizing microfluidic 3D cell culture, we intricately reconstructed the observed abnormal blood vessels in gastric cancer patients in a three-dimensional format, capturing real-time neovasculature. Applying deep learning techniques, we virtually labeled the growing blood vessels with fluorescence, unveiling thin and tortuous morphological characteristics specific to patient iPSCs, distinct from those derived from human umbilical cord endothelial cells. The development of a tumor model, vascularized with cancer cells from the same donor, establishes a versatile testbed for evaluating personalized cancer vascular models. Through comprehensive morphological and functional assessments, this platform facilitates screening for patient-specific combination therapies and holds promise as a model for immune response testing. Citation Format: Jihoon Ko, Noo Li Jeon, Young Sun Oh. Microphysiological modeling of gastric cancer vasculature using iPSC-derived endothelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB387.

Approach and barriers to the assessment and treatment of individuals with co-occurring OCD and PTSD: Treatment providers’ perspectives

Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) frequently co-occur, and phenotypic and functional similarities between the disorders necessitate assessment and treatment considerations by providers. To date, no research has reported on mental health treatment providers’ approach to, and barriers associated with, assessing and treating patients with this complex comorbidity. The present study included 169 mental health providers, the majority of whom were cognitive behaviorally-oriented specialists who had recently treated co-occurring OCD and PTSD. Having a doctorate degree and overall years of experience predicted greater perceived competence to assess and conceptualize co-occurring OCD and PTSD. Recent clinical experience with co-occurring OCD and PTSD predicted perceived competence to conceptualize and treat individuals with both disorders. PTSD specialists perceived themselves as more competent to treat co-occurring OCD and PTSD than non-PTSD specialists. Most providers indicated some barriers to adequate assessment and treatment of individuals with co-occurring OCD and PTSD, including competing priorities and lack of time. Implications of findings are discussed within the context of future training targets to equip providers with the tools needed to conduct comprehensive and accurate diagnostic and functional assessment, as well as provide evidence-based treatment tailored to the unique needs of individuals with co-occurring OCD and PTSD.

Evaluating the contribution of the Glittre-ADL test in adults with cystic fibrosis.

Cardiopulmonary and skeletal muscle impairment and poor physical activity are potential contributors to reduced functional capacity in cystic fibrosis (CF). The Glittre-ADL test (TGlittre) has great potential for clinical use in adult CF adults, as it meets the need for a comprehensive assessment of physical function using tasks similar to activities of daily living. This study aimed to evaluate the performance of TGlittre in CF adults compared to the 6-min walk test (6MWT) and, secondarily, to quantify the associations of their results with pulmonary function, muscle strength, and health-related quality of life (HRQoL). This cross-sectional study evaluated 34 CF adults and compared them with 34 subjects from a control group. The participants underwent the following assessments: functional capacity using TGlittre and 6MWT; spirometry; respiratory muscle strength; handgrip strength (HGS); and HRQoL using the Cystic Fibrosis Questionnaire-Revised (CFQ-R). While CF patients showed a longer time to perform TGlittre compared to controls (134 (119-150) versus 107 (95-126) % of the predicted time p=0.0002), no difference between these groups was observed in the 6MWT. When the second TGlittre was compared to the first TGlittre, there was a significant decrease in total time for both CF patients (p<0.0001) and controls (p=0.0001). TGlittre time correlated with 6MWT distance (6MWD) (rs=-0.641, p<0.0001), HGS (rs=-0.364, p=0.034), peripheral oxygen saturation at the end of the test (rs=-0.463, p=0.006) and the "digestive symptoms" domain of CFQ-R (rs=0.376, p=0.028). TGlittre time was shorter in patients who engaged in regular physical activity (3.10 (2.49-3.39) min versus 3.28 (2.95-3.53) min, p=0.016). TGlittre is more effective than the 6MWT in detecting limitations during exercise. There is an important learning effect of TGlittre in adult CF patients. TGlittre time was correlated with 6MWD, HGS, oxygen saturation level, and the patient's level of physical activity.

'Totality of Evidence' Approach in the Development of GP2017, an Approved Adalimumab Biosimilar.

Hyrimoz®, (GP2017 [SDZ-ADL]), is a biosimilar to Humira® (REF-ADL). SDZ-ADL was approved in 2018 by both the United States Food and Drug Administration (US FDA) and European Medicines Agency (EMA) for the indications of REF-ADL not protected by orphan exclusivity. In 2023, the US FDA and EMA also approved a citrate-free high-concentration formulation (HCF) of SDZ-ADL. Approval of SDZ-ADL was based on data gathered using the US FDA, EMA and World Health Organization (WHO)-recommended step-wise Totality of Evidence approach. This approach is a robust dataset confirming high confidence in analytical, functional, pharmacokinetic (PK) and clinical biosimilarity between the biosimilar and reference medicine determined through analytical and clinical investigation. Evidence supporting the biosimilarity of SDZ-ADL and REF-ADL was reported at each stage of investigation. Comprehensive comparative analytical and functional assessments demonstrated that SDZ-ADL was analytically indistinguishable from REF-ADL in required critical quality attributes, including receptor binding. Phase I clinical data showed PK similarity of SDZ-ADL and REF-ADL in healthy volunteers, with similar safety, tolerability and immunogenicity profiles. Phase III confirmatory efficacy and safety studies, ADACCESS (included in US/EU dossiers) and ADMYRA (separate to US/EU dossiers), both confirmed that SDZ-ADL's efficacy, safety, and immunogenicity matched REF-ADL in all patient groups with no clinically meaningful differences. More recently, this data package was the basis for a citrate-free HCF of SDZ-ADL to be developed, and its PK, safety and immunogenicity were confirmed against the initially approved formulation of SDZ-ADL. Overall, the Totality of Evidence provided for biosimilar adalimumab, SDZ-ADL, confirmed the analytical, functional and clinical similarity of SDZ-ADL to REF-ADL, supporting its regulatory approval and providing a data bridge with which to evaluate and support the approval of citrate-free HCF SDZ-ADL for clinical use.

Endurance exercise preserves physical function in adult and older male C57BL/6 mice: high intensity interval training (HIIT) versus voluntary wheel running (VWR).

Exercise has been shown to improve physical function, mitigate aspects of chronic disease and to potentially alter the trajectory of age-related onset of frailty and sarcopenia. Reliable and valid preclinical models are necessary to elucidate the underlying mechanisms at the intersection of age, exercise, and functional decline. The purpose of this study was to compare, head to head, the effects of two common pre-clinical models of endurance exercise: high intensity interval training (HIIT) and voluntary wheel running (VWR). The hypothesis was that a prescribed and regimented exercise program, HIIT, would prove to be a superior training method to unregulated voluntary exercise, VWR. To investigate this hypothesis, we evaluated adult (n = 24, designated 10m, aged 6 months at the beginning of the study, 10 months at its completion) and older adult (n = 18, designated 26m, aging from 22 months to 26 months over the course of the study) C57BL/6 male mice. These mice were randomly assigned (with selection criteria) to a 13-week program of voluntary wheel running (VWR), high intensity interval training (HIIT), or sedentary control (SED). The functional aptitude of each mouse was determined pre- and post-training using our composite CFAB (comprehensive functional assessment battery) scoring system consisting of voluntary wheel running (volitional exercise and activity rate), treadmill (endurance), rotarod (overall motor function), grip meter (forelimb strength), and inverted cling (whole body strength/endurance). To measure sarcopenia, we tracked body mass, body composition (with EchoMRI), plantar flexor torque (in 10m), and measured muscle wet mass post-training. Overall, adult CFAB scores decreased while body mass and percent body fat increased as they matured; however, exercise significantly mitigated the changes (p < 0.05) compared to SED. Older adults demonstrated preservation of function (CFAB) and reduced body fat (p < 0.05) compared to SED. To conclude, both types of exercise maintained physical function equally in older mice.

Sarcopenia as the Mobility Phenotype of Aging: Clinical Implications.

Sarcopenia, which is characterized by an age-related decline in muscle mass and function, poses significant challenges to geriatric care. Its definition has evolved from muscle-specific criteria to include muscle mass, muscle function, and physical performance, recognizing sarcopenia as a physical frailty. Sarcopenia is associated with adverse outcomes, including mortality, falls, fractures, cognitive decline, and admission to long-term care facilities. Neuromechanical factors, protein-energy balance, and muscle protein synthesis-breakdown mechanisms contribute to its pathophysiology. The identification of sarcopenia involves screening tests and a comprehensive assessment of muscle mass, strength, and physical function. Clinical approaches aligned with the principles of comprehensive geriatric assessment prioritize patient-centered care. This assessment aids in identifying issues related to activities of daily living, cognition, mood, nutrition, and social support, alongside other aspects. The general approach to factors underlying muscle loss and functional decline in patients with sarcopenia includes managing chronic diseases and evaluating administered medications, with interventions including exercise and nutrition, as well as evolving pharmacological options. Ongoing research targeting pathways, such as myostatin-activin and exercise mimetics, holds promise for pharmacological interventions. In summary, sarcopenia requires a multifaceted approach, acknowledging its complex etiology and tailoring interventions to individual patient needs.