Direct and Indirect Chimeric Antigen Receptor T-Cell Imaging with PET/MRI in a Tumor Xenograft Model.

Background Chimeric antigen receptor (CAR) T cells are a promising cancer therapy; however, reliable and repeatable methods for tracking and monitoring CAR T cells in vivo remain underexplored. Purpose To investigate direct and indirect imaging strategies for tracking the biodistribution of CAR T cells and monitoring their therapeutic effect in target tumors. Materials and Methods CAR T cells co-expressing a tumor-targeting gene (anti-CD19 CAR) and a human somatostatin receptor subtype 2 (hSSTr2) reporter gene were generated from human peripheral blood mononuclear cells. After direct labeling with zirconium 89 (89Zr)-p-isothiocyanatobenzyl-desferrioxamine (DFO), CAR T cells were intravenously injected into immunodeficient mice with a CD19-positive and CD19-negative human tumor xenograft on the left and right flank, respectively. PET/MRI was used for direct in vivo imaging of 89Zr-DFO-labeled CAR T cells on days 0, 1, 3, and 7 and for indirect cell imaging with the radiolabeled somatostatin receptor-targeted ligand gallium 68 (68Ga)-DOTA-Tyr3-octreotide (DOTATOC) on days 6, 9, and 13. On day 13, mice were euthanized, and tissues and tumors were excised. Results The 89Zr-DFO-labeled CAR T cells were observed on PET/MRI scans in the liver and lungs of mice (n = 4) at all time points assessed. However, they were not visualized in CD19-positive or CD19-negative tumors, even on day 7. Serial 68Ga-DOTATOC PET/MRI showed CAR T cell accumulation in CD19-positive tumors but not in CD19-negative tumors from days 6 to 13. Notably, 68Ga-DOTATOC accumulation in CD19-positive tumors was highest on day 9 (mean percentage injected dose [%ID], 3.7% ± 1.0 [SD]) and decreased on day 13 (mean %ID, 2.6% ± 0.7) in parallel with a decrease in tumor volume (day 9: mean, 195 mm3 ± 27; day 13: mean, 127 mm3 ± 43) in the group with tumor growth inhibition. Enhanced immunohistochemistry staining of cluster of differentiation 3 (CD3) and hSSTr2 was also observed in excised CD19-positive tumor tissues. Conclusion Direct and indirect cell imaging with PET/MRI enabled in vivo tracking and monitoring of CAR T cells in an animal model. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Bulte in this issue.

Effects of Prolonged Sitting with Slumped Posture on Trunk Muscular Fatigue in Adolescents with and without Chronic Lower Back Pain.

Background and Objectives: This study investigated the effects of prolonged sitting on trunk muscular fatigue and discomfort in participants with and without chronic lower back pain (LBP). Material and Methods: This study included 15 patients with LBP and 15 healthy controls. All participants were instructed to sit on a height-adjustable chair with their knee and hip joints bent at 90° for 30 min, in slumped sitting postures. Surface electromyography was used to assess the median frequency of the internal obliques (IO)/transversus abdominis (TrA) and multifidus (MF) muscles. Perceived discomfort was measured using a Borg category ratio-scale. Median frequency of the trunk muscles and perceived discomfort after 30 min of sitting were compared with baseline. Result: There were no significant differences within the group and between both groups in the median frequency of bilateral IO and MF muscles. The LBP group showed significantly greater perceived discomfort after prolonged sitting, as compared to the control group. Conclusions: Prolonged sitting with slumped posture could increase the risk of experiencing lower back discomfort.

The reliability and validity of the Korean version of the lower limb functional index.

[Purpose] The purpose of this study was to establish the reliability and validity of the Korean-translated version of the Lower Limb Functional Index (LLFI) in the assessment of patients with lower-limb disorders. [Subjects and Methods] Fifty-six subjects with lower-limb disorders, 24 men and 32 women, participated in this study. Reliability was determined by using the intra-class correlation coefficient and Cronbach's α for internal consistency. Validity was examined by correlating the LLFI scores with the Lower Extremity Functional Scale (LEFS) and Short Form 36 (SF-36) scores. [Results] The test-retest reliability was 0.95. The criterion-related validity was established through a comparison with the Korean versions of the LEFS and SF-36. [Conclusion] The Korean version of the LLFI was shown to be a reliable and valid instrument for assessing lower-limb complaints.

Effect of a cervical support pillow on sternocleidomastoid activity and satisfaction in asymptomatic participants.

[Purpose] The aim of this study was to examine the changes in sternocleidomastoid muscle (SCM) activity when using a cervical support pillow (CSP) and to determine the pillow's effect on satisfaction in asymptomatic participants. [Subjects and Methods] This study followed a cross-over design and the order of the measurements was counterbalanced. Twenty asymptomatic participants were positioned supine for 5 minutes by using either a CSP or a general pillow (GP) while the activity of the SCM was measured using surface electromyography. [Results] The CSP significantly decreased the activity of the SCM compared with the GP, and satisfaction after use of the CSP was significantly greater than that after use of the GP. [Conclusion] This study suggests that the CSP may be effective in preventing unnecessary neck muscle activation during sleep in asymptomatic people.

Effects of chin tuck exercise using neckline slimmer device on suprahyoid and sternocleidomastoid muscle activation in healthy adults.

[Purpose] This study investigated the effect of chin tuck exercise (CTE) using a neckline slimmer device on suprahyoid (SH) and sternocleidomastoid (SCM) muscle activation in healthy adults. [Subjects and Methods] We measured activation of the SH and SCM muscles using surface electromyography in 20 healthy adults during head lift exercise (HLE) and CTE using a neckline slimmer device. The order of exercises was randomized and the mean and peak values of each muscle's activation were assessed. [Results] During the CTE using a neckline slimmer device, SH activation was significantly greater and SCM activation was significantly lower than during the HLE. [Conclusion] This study suggest that chin-tuck exercise using a neckline slimmer device may be more helpful than HLE for swallowing training.

Effects of lumbar lordosis assistive support on craniovertebral angle and mechanical properties of the upper trapezius muscle in subjects with forward head posture.

[Purpose] The aim of this study was to investigate the effect of lumbar lordosis assistive support (LLAS) on craniovertebral angle (CVA) and mechanical properties of the upper trapezius (UT) muscle in subjects with forward head posture (FHP). [Subjects and Methods] This study recruited 20 subjects with FHP. CVA and muscle tone, viscoelasticity, and stiffness of the UT were measured using Myoton in all subjects in a sitting position with LLAS and in a neutral sitting position. The order of measurements was randomized and the mean values were calculated twice. [Results] The sitting position with LLAS showed a significantly greater improvement than the neutral sitting position with regard to CVA and muscle tone, viscoelasticity, and stiffness of the UT. [Conclusion] We suggest that the sitting position using LLAS induces the maintenance of normal neck posture and a reduction in the muscle tone of the UT in the subjects with FHP.

Effects of expiratory muscle strength training on swallowing function in acute stroke patients with dysphagia.

[Purpose] This study was conducted to identify the effects of expiratory muscle strength training on swallowing function in acute stroke patients with dysphagia. [Subjects and Methods] A total of 18 stroke patients with dysphagia were enrolled in the study. All participants were randomly assigned to either an experimental group (n=9) or a control group (n=9). All participants performed traditional-swallowing rehabilitation therapy in 30-minute sessions five times a week for four weeks; however, only the experimental group received expiratory muscle strength training. [Results] Both groups showed significant improvements after mediation. When compared with the control group, the functional dysphagia scale, vallecular residue, and penetration-aspiration scale were significantly improved in the experimental group. [Conclusion] Expiratory muscle strength training is an effective intervention for impaired swallowing function in acute strike patients with dysphagia.

The effects of task-oriented training on hand dexterity and strength in children with spastic hemiplegic cerebral palsy: a preliminary study.

[Purpose] The purpose of this study was to investigate the effects of task-oriented training (TOT) on hand dexterity and strength in children with spastic hemiplegic cerebral palsy. [Subjects and Methods] Twelve children with spastic hemiplegic cerebral palsy were randomly assigned to either the TOT group (n=6) or the control group (n=6). In both groups, conventional occupational therapy was performed 40-min/day, 2 times a week, for 4 weeks. In the TOT group, TOT was additionally performed for 20 min, and the control group received usual care. The box and block test (BBT) was performed to assess hand dexterity. Hand strength was also assessed using hand dynamometer. [Results] After intervention, the TOT group showed a significant improvement of hand dexterity. In the control group, BBT and grip strength were not significantly improved after intervention. [Conclusion] In clinical settings, we suggest that TOT may be used as an intervention to improve hand dexterity in children with spastic hemiplegic cerebral palsy.

The reliability and validity of the Korean version of the foot function index for patients with foot complaints.

[Purpose] The purpose of this study was to establish the reliability and validity of the Foot Function Index translated into Korean for use in patients with plantar fasciitis and foot/ankle fracture. [Subjects and Methods] Thirty-six subjects with foot complaints, 14 males and 22 females, participated in the study. Reliability was determined by using the intra-class correlation coefficient and Cronbach's alpha for internal consistency. Validity was examined by correlating Foot Function Index scores with the Short Form-36 and the Visual Analog Scale scores. [Results] Test-retest reliability was 0.90 for the pain subscale, and 0.94 and 0.91 for the disability and activity limitation subscales, respectively. The criterion-related validity was established by comparison with the Korean version of the Short Form-36 and Visual Analog Scale. [Conclusion] The Korean version of the Foot Function Index was shown to be a reliable and valid instrument for assessing foot complaints.

Immediate effects of Graston Technique on hamstring muscle extensibility and pain intensity in patients with nonspecific low back pain.

[Purpose] The purpose of this study was to analyze the effect of Graston Technique on hamstring extensibility and pain intensity in patients with nonspecific low back pain. [Subjects and Methods] Twenty-four patients with nonspecific low back pain (27-46 years of age) enrolled in the study. All participants were randomly assigned to one of two groups: Graston technique group (n=12) and a static stretching group (n=12). The Graston Technique was used on the hamstring muscles of the experimental group, while the static stretching group performed static stretching. Hamstring extensibility was recorded using the sit and reach test, and a visual analog scale was used to measure pain intensity. [Results] Both groups showed a significant improvement after intervention. In comparison to the static stretching group, the Graston technique group had significantly more improvement in hamstring extensibility. [Conclusion] The Graston Technique is a simple and effective intervention in nonspecific low back pain patients to improve hamstring extensibility and lower pain intensity, and it would be beneficial in clinical practice.

The reliability and validity of the Korean version of the Upper Limb Functional Index.

[Purpose] The purpose of this study was to establish the reliability and validity of Upper Limb Functional Index (ULFI), which has been translated into Korean, in treating patients with upper limb complaints. [Subjects and Methods] Fourty-nine subjects with upper limb disorder, 20 males and 29 females, participated in this study. Reliability was determined by using the intra class correlation coefficient and Cronbach's alpha for internal consistency. Validity was examined by correlating ULFI scores with Disability of Arm, Shoulder and Hand (DASH). [Results] Test-retest reliability was 0.90. The criterion-related validity was established by a comparison with the Korean version of DASH. [Conclusion] The Korean version of ULFI was shown to be a reliable and valid instrument for assessing upper limb complaints.

The reliability and validity of the Korean version of the Japanese orthopaedic association back pain evaluation questionnaire.

[Purpose] The purpose of this study was to establish the reliability and validity of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) translated into Korean for use with patients' low back pain. [Subjects and Methods] Sixty-two subjects with low back pain, 28 men and 34 women, participated in the study. Reliability was determined by using the intra class correlation coefficient and Cronbach's alpha for internal consistency. Validity was examined by correlating the JOABPEQ scores with the 36 item short form health survey (SF 36). [Results] Test-retest reliability was 0.75-0.83. The criterion-related validity was established by comparison with the Korean version of the SF 36. [Conclusion] The Korean version of the JOABPEQ was shown to be a reliable and valid instrument for assessing low back pain.

The effects of spinal support device on pain and extensibility of the hamstrings in patients with non-specific low back pain.

[Purpose] The objective of this study was to investigate the effects of spinal support device (SSD) on pain and hamstring extensibility in patients with non-specific low back pain (NSLBP). [Subjects and Methods] 20 patients with NSLBP were recruited and randomly assigned to either the SSD group or the control group. In the SSD group, SSD was applied; in the control group, bed rest in supine position was performed. Both groups underwent treatment 20 min/day, 3 times a week, for a duration of 4 weeks. To assess the hamstring extensibility, sit and reach test (SRT) was performed. To assess pain pressure threshold (PPT) of the sacroiliac joint, a pressure algometer was used. Visual analog scale (VAS) was used to quantify pain. [Results] The SSD group showed a significant improvement in sacroiliac joint pain with increased VAS, and the control group showed a significantly increased VAS after intervention. In the SSD group, VAS was significantly increased, but SRT was not changed compared with the control group. [Conclusion] These results demonstrated that an application of SSD effectively attenuates low back pain. Therefore, SSD may be a suitable intervention for pain control in patients with NSLBP.

Effects of neurofeedback and computer-assisted cognitive rehabilitation on relative brain wave ratios and activities of daily living of stroke patients: a randomized control trial.

[Purpose] This study investigated the effects of neurofeedback (NFB) and computer-assisted cognitive rehabilitation (CACR) on the relative brain wave ratios and activities of daily living (ADL) of stroke patients. [Subjects and Methods] Forty-four participants were randomly allocated to the NFB (n=14), CACR (n=14), or control (CON) (n=16) groups. Two expert therapists provided the NFB, CACR, and CON groups with traditional rehabilitation therapy in 30-minute sessions, 5 times a week, for 6 weeks. NFB training was provided only to the NFB group and CACR training was provided only to the CACR group. The CON group received traditional rehabilitation therapy only. Before and after 6 weeks of intervention, brain wave and ADL evaluations were performed, and the results were analyzed. [Results] The relative ratio of beta waves, only showed a significant increase in the frontal and parietal areas of the NFB group. Significant changes in ADL were shown by all three groups after the intervention. However, there were no significant differences between the NFB and CACR groups and the CON group. [Conclusion] Our results suggest that CACR and NFB are effective at improving cognitive function and ADL of stroke patients.

Reliability and validity of the Korean version of the Short Musculoskeletal Function Assessment questionnaire for patients with musculoskeletal disorder.

[Purpose] The purpose of this study was to establish the reliability and validity of the Short Musculoskeletal Function Assessment questionnaire, which was translated into Korean, for patients with musculoskeletal disorder. [Subjects and Methods] Fifty-five subjects (26 males and 29 females) with musculoskeletal diseases participated in the study. The Short Musculoskeletal Function Assessment questionnaire focuses on a limited range of physical functions and includes a dysfunction index and a bother index. Reliability was determined using the intraclass correlation coefficient, and validity was examined by correlating short musculoskeletal function assessment scores with the 36-item Short-Form Health Survey (SF-36) score. [Results] The reliability was 0.97 for the dysfunction index and 0.94 for the bother index. Validity was established by comparison with Korean version of the SF-36. [Conclusion] This study demonstrated that the Korean version of the Short Musculoskeletal Function Assessment questionnaire is a reliable and valid instrument for the assessment of musculoskeletal disorders.

Effects of visual feedback with a mirror on balance ability in patients with stroke.

[Purpose] This study aimed to examine the effects of a visual feedback obtained from a mirror on balance ability during quiet standing in patients with stroke. [Subjects] Fifteen patients with stroke (9 males, 6 females) enrolled in the study. [Methods] Experimental trials (duration, 20s) included three visual conditions (eyes closed, eyes open, and mirror feedback) and two support surface conditions (stable, and unstable). Center of pressure (COP) displacements in the mediolateral and anteroposterior directions were recorded using a force platform. [Results] No effect of condition was observed along all directions on the stable surface. An effect of condition was observed on the unstable surface, with a smaller mediolateral COP distance in the mirror feedback as compared to the other two conditions. Similar results were observed for the COP speed. [Conclusion] Visual feedback from a mirror is beneficial for improving balance ability during quiet standing on an unstable surface in patients with stroke.

Effects of computer assisted cognitive rehabilitation on brain wave, memory and attention of stroke patients: a randomized control trial.

[Purpose] This study investigated brain wave, memory and attention changes in adult stroke patients using computer assisted cognitive rehabilitation (CACR). [Subjects] Twenty-five stroke patients were randomly allocated to either the CACR group (n=12) or the control group (n=13). [Methods] Two expert therapists provided the CACR group and the control group with traditional rehabilitation therapy in 30-minute sessions, semi-weekly, for 6 weeks. CACR was provided only to the CACR group. The control group received traditional rehabilitation therapy only. Before and after the 6 weeks of intervention, electroencephalography (EEG) and a computerized neurocognitive function test (CNT) were performed, and the results were analyzed. [Results] After the intervention, the CACR group showed significant differences in the frontal lobe (Fp1, Fp2, and F4) and in the parietal lobe (P3 and P4), and also showed significant differences in CNT memory (DST and VST forward/backward test) and attention (VCPT correct responses), but no notable changes were observed in the control group. [Conclusion] These results suggest that CACR is feasible and suitable for individuals with stroke. Detailed and diverse investigations should be performed considering the numbers and characteristics of subjects, and the limitations affecting the CACR training period.

Effects of Transcutaneous Electrical Nerve Stimulation with Taping on Wrist Spasticity, Strength, and Upper Extremity Function in Patients with Stroke: A Randomized Control Trial.

Objective: Six months after the onset of stroke, over 60% of patients experience upper limb dysfunction, with spasticity being a major contributor alongside muscle weakness. This study investigated the effect of transcutaneous electrical nerve stimulation (TENS) with taping on wrist spasticity, strength, and upper extremity function in patients with stroke. Methods: In total, 40 patients with stroke were included and randomly divided into two groups: the TENS + taping (n = 20, age 52.4 ± 9.3 (range: 39 to 70)) and TENS (n = 20, age 53.5 ± 10.8 (range: 39 to 74)) groups. All subjects performed 30 sessions of task-related training, which included 10 min of postural control training and 20 min of task performance. Additionally, all subjects received TENS on the spastic muscle belly for 30 min before task-related training. In the TENS + taping group, taping was additionally applied to the forearm and wrist but not in the TENS group. The Modified Ashworth Scale was used to measure spasticity, and a handheld dynamometer was used to measure muscle strength. The Fugl-Meyer Assessment of Upper Extremity was used to evaluate the functional ability of the upper extremity. Results: In the TENS + taping group, spasticity and upper extremity function were significantly improved as compared to those in the TENS group (p < 0.05). However, no significant difference in muscle strength was observed between the two groups (p > 0.05). Conclusions: This study demonstrated that the combination of TENS and taping for spasticity and function of the upper extremity was more effective in relieving the spasticity than TENS alone. Therefore, we suggest this combination as an additional treatment for spasticity and function of the upper extremity.

Tobacco-induced hyperglycemia promotes lung cancer progression via cancer cell-macrophage interaction through paracrine IGF2/IR/NPM1-driven PD-L1 expression.

Tobacco smoking (TS) is implicated in lung cancer (LC) progression through the development of metabolic syndrome. However, direct evidence linking metabolic syndrome to TS-mediated LC progression remains to be established. Our findings demonstrate that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene (NNK and BaP; NB), components of tobacco smoke, induce metabolic syndrome characteristics, particularly hyperglycemia, promoting lung cancer progression in male C57BL/6 J mice. NB enhances glucose uptake in tumor-associated macrophages by increasing the expression and surface localization of glucose transporter (GLUT) 1 and 3, thereby leading to transcriptional upregulation of insulin-like growth factor 2 (IGF2), which subsequently activates insulin receptor (IR) in LC cells in a paracrine manner, promoting its nuclear import. Nuclear IR binds to nucleophosmin (NPM1), resulting in IR/NPM1-mediated activation of the CD274 promoter and expression of programmed death ligand-1 (PD-L1). Restricting glycolysis, depleting macrophages, or blocking PD-L1 inhibits NB-mediated LC progression. Analysis of patient tissues and public databases reveals elevated levels of IGF2 and GLUT1 in tumor-associated macrophages, as well as tumoral PD-L1 and phosphorylated insulin-like growth factor 1 receptor/insulin receptor (pIGF-1R/IR) expression, suggesting potential poor prognostic biomarkers for LC patients. Our data indicate that paracrine IGF2/IR/NPM1/PD-L1 signaling, facilitated by NB-induced dysregulation of glucose levels and metabolic reprogramming of macrophages, contributes to TS-mediated LC progression.