Spatial transcriptomic profiling reveals body site-specific inflammatory differences in psoriasis lesions

Psoriasis is a common chronic inflammatory skin disease. A variety of treatment options lead to substantial improvement of most psoriasis plaques; however, recurrence of psoriasis in previously affected areas is common. Additionally, it can be challenging to reach disease resolution in certain hard-to-treat areas such as scalp and lower extremity (LE). Here, we map histologic and spatial transcriptomic differences between psoriasis lesions across different anatomical locations, to understand if differences in the inflammatory profile can be linked to plaque-site-specific treatment resistance. Quantitative immunohistochemical analysis and transcriptomic digital spatial profiling were performed on skin punch biopsies obtained from unaffected areas on the trunk, lesional areas of the scalp, upper extremity, and LE of 12 patients with psoriasis. Histological analysis showed no significant differences in epidermal thickness among lesional (LS) skin from different body locations. Immunohistochemical markers (CD3, CD4, CD8, CD103, CD207, RORγt, FOXP3 and MPO) were higher in LS skin compared with non-lesional (NL) skin but did not differ significantly between LS sites. Whole transcriptome spatial RNA profiling identified several differentially expressed genes that distinguished LS from NL skin and revealed site-specific transcriptomic differences. Notably, IL-23 signalling was significantly enriched in the LE epidermis, and IL-17 signalling was more pronounced in the epidermis of LS samples. These findings highlight minimal histological and immunohistochemical variation, yet significant transcriptomic and pathway differences between psoriasis body locations, suggesting potential future targets for site-specific therapeutic strategies.

Background/Introduction Pulmonary embolism (PE) is caused by blockage of pulmonary arteries by thrombus. The sources of thrombus are thought to be mostly veins in lower extremities, whereas deep vein thrombosis (DVT) in upper extremities rarely occurs spontaneously. Recent studies reported that DVT in upper extremities might have significant complications, and DVT in upper extremities could be increasing. However, there is a paucity of data on patients with DVT in upper extremities, leading to uncertainty in optimal treatment strategies including anticoagulation therapy. Purpose We sought to evaluate the clinical characteristics, management strategies, and long-term outcomes of patients with DVT in upper extremities in a large observational database in Japan. Methods The COMMAND VTE Registry is a multicenter registry enrolling 3027 consecutive patients with acute symptomatic venous thromboembolism (VTE) objectively confirmed by imaging examination or by autopsy among 29 centers in Japan between January 2010 and August 2014. The current study population consisted of 2498 patients with DVT in upper or lower extremities, after excluding 381 patients with PE only, 144 patients who had thrombus in locations other than upper or lower extremities, and 4 patients with DVT in both upper and lower extremities. The study patients were divided into 2 groups: patients with DVT in upper extremities and patients with DVT in lower extremities. We compared the clinical characteristics, management strategies and long-term outcomes between the 2 groups. Results There were 74 patients (3.0%) with upper extremities DVT and 2498 patients (97%) with lower extremities DVT. Patients with upper extremities DVT more often had active cancer at diagnosis (58%) and central venous catheter use (22%). The proportion of concomitant PE at diagnosis was lower in patients with upper extremities DVT than in those with lower extremities DVT (14% and 51%, P<0.001). Discontinuation of anticoagulation therapy was more frequent in patients with upper extremities DVT (63.8% and 29.8% at 1-year, P<0.001). The cumulative 3-year incidence of recurrent VTE was not different between the 2 groups (9.8% and 7.4%, P=0.43) (Figure). After adjusting confounders, the risks of upper extremities DVT relative to lower extremities DVT for recurrent VTE remained insignificant (HR 0.94, 95% CI 0.36–2.01, P=0.89). Kaplan-Meier event curves for recurrence Conclusions The prevalence of patients with DVT in upper extremities was 3.0% in the current large-scale real-world registry. Patients with DVT in upper extremities more often had active cancer at diagnosis and central venous catheter use as a transient risk factor for VTE, and less often had concomitant PE. Patients with DVT in upper extremities had similar long-term risk for recurrent VTE as those with DVT in lower extremities despite shorter duration of anticoagulation. Acknowledgement/Funding Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

BackgroundFabry disease (FD) is a rare, progressive disorder caused by pathogenic variants of the GLA gene resulting in the accumulation of toxic metabolites. Pain is a hallmark of FD, and patients often present with heterogeneous pain profiles. This cross-sectional, web-based survey was conducted to characterize pain and pain crises in patients with FD in the United States and explore the effects of sex, disease phenotypes, and treatment on pain.ResultsA total of 66 participants (mean ± standard deviation [SD] age: 44.0 ± 12.7 years; females: 59.1%) completed the survey. Participants reported experiencing pain in upper (34.8%) and lower (43.9%) extremities several times a day and abdominal pain (31.8%) a few times a week. Overall, participants reported the nature of their pain as triggered (upper extremities: 47.0%; abdomen: 51.5%) or sudden (lower extremities: 57.6%). Female participants reported experiencing pain in upper (46.2%) and lower (48.7%) extremities several times a day and described it as sudden or triggered (48.7%) in upper extremities and sudden (61.5%) in lower extremities. Pain crises were reported in the lower extremities (80.0%), followed by the upper extremities (66.7%) and the abdomen (51.1%), and were often characterized as burning, tingling, or stabbing. A higher proportion of female participants (84.6%) than that of male participants (73.7%) reported pain crises in lower extremities. The duration of pain crises varied from 30 min to several days for different subgroups depending on sex and FD phenotypes. Most participants (81.0%) reported symptom improvement after 12 months of FD-specific treatment. Participants reported improvement in neuropathic symptoms (burning in hands, 45.9%), with an overall mean (± SD) satisfaction score of 7.2 (± 1.7) with agalsidase beta as the most recent medication.ConclusionsPain was largely reported to be triggered across all subgroups. Consistent pain profiles were noted in participants across sex and FD phenotypes. Female participants reported pain burden similar to that of male participants, and pain crisis experience was heterogeneous across the subgroups. Most participants reported improvement in symptoms after FD-specific treatment and a high treatment satisfaction score with agalsidase beta.

Current evidence indicates a strong relation between improved visuomotor choice reaction time (VMRT) and a reduced risk of lower extremity injury, making both lower- and upper extremity VMRT training paradigms valuable to athletes. This investigation studied as yet unconfirmed crossover effects of upper extremity training on lower extremity performance; and we evaluated underlying relevant perceptual and cognitive adaptations. In this three-armed, randomized, controlled intervention, we used a computerized training device to compare participants receiving four weeks of upper (n = 12) and lower (n = 12) extremity VMRT training with a control group (n = 13) of healthy participants. Collectively, our participants had a mean age of 24.6 years (SD = 2.2), a mean height of 173 cm (SD = 10), and a mean weight of 69.6 kg (SD = 12.1); 57% (n = 21) were female and 43% (n = 16) were male. We assessed participants' upper and lower extremity VMRT performance and domain-specific perceptual and cognitive abilities before and after intervention and analyzed differences between their before and after performances. Lower extremity training enhanced VMRT performances for both lower extremity and crossover upper extremity. Upper extremity training improved VMRT for upper extremity and increased cognitive choice reaction performance but yielded no crossover effects to lower extremity. We found no effects of VMRT training on other domain-specific cognitive performance markers (attention, executive function, memory, or working memory). VMRT training modulated only task-specific cognitive performance and induced crossover effects from lower extremity training to upper extremity performance but not vice versa.

INTRODUCTION: Distal vascularized lymph node (VLN) transfers are becoming recognized as a valuable surgical option to treat extremity lymphedema. Native lymphedematous tissue may impact the quality, location and reliability of recipient vessels in the distal upper and lower extremity. The purpose of this study was to review the characteristics of recipient vessels in order to more accurately predict peri-operative events. METHODS: An IRB-approved review of a prospective database was performed for patients who underwent distal VLN transfer for upper and lower extremity lymphedema. Pre-operative duplex ultrasonography and intra-operative findings of the recipient sites for all distal VLN transfers were evaluated. Findings related to artery, superficial and deep venous vessel diameter, vessel choice, and vascular-related complications were reviewed. RESULTS: Sixty cases of distal VLN transfer were evaluated; 55% lower extremity, 45% upper extremity. In the lower extremity, a majority of transfers (94%) were placed around the ankle region, while two patients received transfers to the proximal leg. Vascular systems used included the posterior tibial (60.6%), the anterior tibial (33.3%), and the medial sural (6.1%) arteries. Average artery diameters were similar around the ankle (3.0mm), and were 2mm for the medial sural artery. The deep and superficial venous systems were used in equal portions, with a smaller proportion using combined systems. Vascular complications occurred in 27.3% of cases, but no site-specific differences were found. In the upper extremity, distal forearm/wrist received a majority of transfers (89%), while three patients received transfers to the elbow region. Recipient vessels included the radial artery-deep branch (59.3%), ulnar artery (29.6%), and ulnar collateral artery (11.1%). Average artery (2.3mm) and vein diameter (2.5mm) were similar in the upper extremity transfers. When specifically evaluating select recipient sites, the volar wrist had a significantly smaller average vein diameter (2.0mm) as compared to other sites (p=0.04) and less frequent use of the superficial venous system as outflow (p=0.02). Combined, these resulted in a significantly greater occurrence of venous congestion (p=0.03). CONCLUSIONS: Recipient vessels for distal VLN transfers are reliably and predictably present. In the setting of a lymphedematous extremity, deep arterial systems appear to be relatively unaffected, with medium caliber average vessel diameters. Regional differences appear to exist for the usability and selection of recipient veins in various locations.

Introduction Severe frostbite injury can lead to significant long-term functional impairments. This study aims to assess long-term function and symptom resolution in upper vs. lower extremity frostbite. We hypothesize that symptom resolution is slower in upper extremity injury and need for functional assistance is higher in lower extremity injury. Methods A longitudinal cohort of 182 severe frostbite injured patients, defined with a post-rewarming perfusion deficit on imaging and/or clinical diagnosis, included 137 patients with isolated upper or lower extremity injury. Analyses were stratified by amputation and only included those with documented symptoms (neurogenic pain, edema, and numbness) or need for functional assistance (aid with activities of daily living (ADLs) or ambulation) at discharge. Logistic regression was performed to assess need for functional assistance and Cox regression analyzed time to symptom resolution. Results There were equal distribution between upper extremity (51%) and lower extremity (49%) frostbite injuries. Most upper (61%) and lower (66%) extremity injured patients needed assistance at discharge. The overall rate of amputation was 27%, (33% lower and 21% upper, p = 0.133). In patients without amputations, logistic regression showed no significant difference in functional assistance need between upper and lower extremity injuries (OR 1.32, p=0.709). However, among those with amputations, lower extremity injuries were associated with significantly worse functional outcomes (OR 21.67, p=0.008). Cox regression showed non-significant differences in time to symptom resolution between upper and lower extremity injuries in non-amputees (fig 1) and amputees (fig 2). Conclusions This study offers a novel analysis of extremity-specific outcomes, providing new insights into functional recovery and symptom resolution in the largest contemporary cohort of severe frostbite patients. Lower extremity amputees required more functional assistance, while no significant differences in symptom resolution were observed between upper and lower extremity injuries. These findings can guide tailored rehabilitation strategies, enhance functional outcomes, and improve resource allocation in burn care settings. Future research should explore whether limited access to assistive devices, particularly for upper extremity amputees, contributes to differing outcomes. Applicability of Research to Practice Collaborative efforts to delineate access to assistive-devices and define standard symptom measurements in frostbite injuries may help improve functional outcomes in this high need, low resourced population. Funding for the Study N/A

Background and Study Aim. In this study, it is aimed to evaluate the power and force parameters of lower and upper extremities of the individual and team athletes who practice different branches. Material and Methods. 32 elite athletes, most of whom are university students, with an average age of 21.16 ± 2.08, who are active in sports, participated in the study. The groups were formed from Boxing and Handball (BG and HG) branches in which the upper extremities are used predominantly and from Taekwondo and Football (TG and FG) branches in which the lower extremities are used predominantly. The anaerobic power values of each individual’s upper and lower extremities were measured by a Monark 894E. The isokinetic force values of dominant arms and legs were measured by a Cybex humac norm device. Results. After examination of the data it was found that the upper extremity power values of BG and HG were significantly higher than TG when the top values of peak powers (PP) were evaluated. In the evaluations with respect to leg 60°/s and 180°/s extension and flexion; HG and FG was significantly higher than TG in 60°/s extension at PP; HG and FG were significantly indifferent but they were significantly higher than BG and TG in 60°/s flexion at PP. In the comparisons of the groups’ 60°/s and 180°/s extension and flexion values of lower extremities anaerobic power and isokinetic force and lower extremities’ wingate values, a number of positive relations were found between all of the groups. All of the groups were positively related to each other in terms of upper extremities wingate and 60°/s, 180°/s internal and external isokinetic forces. Conclusions. Both the isokinetic arm force values and arm wingate levels were higher in the branches in which the upper extremities are used predominantly than the branches in which the lower extremities are used predominantly. On the other hand, the difference seen in the upper extremities was not seen in the lower extremities.

The anatomical location and somatotopic organization of the corticospinal tract (CST) in the corona radiata (CR) of the normal human brain have not been studied using diffusion tensor tractography so far. In this study, the anatomical location and somatotopic organization of the CST in the CR were evaluated by determining the highest probabilistic locations and distances between the upper and lower extremities in the slices of upper and lower CR in the brain. In the mediolateral direction, the average of the highest probabilistic locations for the upper and lower extremities were 40.27 and 37.16% at the upper CR level and 38.19 and 37.14% at the lower CR level, respectively. In the anteroposterior direction, the average of the highest probabilistic locations for the upper and lower extremities were 62.52 and 75.65% at the upper CR level and 60.19 and 68.12% at the lower CR level, respectively. The average distances between upper and lower extremities for the mediolateral direction were 2.41 mm at the upper CR level and 1.21 mm at the lower CR level. The average distances between upper and lower extremities for the anteroposterior direction were 5.23 mm at the upper CR level and 4.47 mm at the lower CR level, respectively. Our findings suggest that the anatomical location and somatotopic organization for the upper extremity are located anterolaterally to the lower extremity in the CR of a normal human brain and distances between the upper and lower extremities become decreased as the CST descends from the upper to the lower CR level.

OBJECTIVES: Peak torque expresses a point output which may, but does not always, correlate well with full range output measures such as work or power, particularly in a rehabilitating muscle....

BackgroundRhabdomyosarcoma (RMS) of the extremities has a particularly poor prognosis compared to other primary sites due to an increased rate of alveolar histology, higher rate of metastasis, and the extent of regional lymph node involvement. To date there are few assessments comparing upper extremity (UE) to lower extremity (LE) RMS of the extremities using population-based registry, so we sought to compare survival between UE and LE RMS.Materials and methodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, cases of RMS of the UE and LE diagnosed between 2000–2020 were collected. Descriptive statistics and chi-square analyses were completed for one-and five-year survival. Log-rank and Cox regression analyses were completed to compare UE versus LE survival.ResultsA total of 641 cases were included, of which 221 (34.5%) were UE and 420 (65.5%) were LE. On log-rank tests, UE survival was longer than LE survival (p = 0.021). The one-year survival rate was greater for the UE (88.7%) compared to the LE (81.4%) (p = 0.020) but similar at five-years. Cox regression analysis showed no difference in survival between UE and LE primary site (hazard ratio = 1.172, p = 0.322).ConclusionsIn comparing UE and LE RMS survival, UE survival was greater at one-year, but not on adjusted analyses. These findings contribute to the few prior assessments of outcomes between UE and LE RMS, though direct comparisons between UE and LE should be included in future prospective studies.

ObjectiveRobot-assisted neuro-rehabilitation therapy plays a central role in upper extremity recovery of stroke. However, the efficacy of robotic training on the upper extremity is not yet well defined, and little attention has been devoted to its potential effect on the lower extremity. The aim of this study was to compare the efficacy of robot-assisted training and therapist-mediated enhanced upper extremity therapy on the upper and lower extremities.MethodsA randomized clinical trial involving 172 stroke survivors was conducted in China. All participants received either robot-assisted training or enhanced upper extremity therapy for 3 weeks. Fugl-Meyer assessment upper extremity subscale (FMA-UE), Fugl-Meyer assessment lower extremity subscale (FMA-LE), and Modified Barthel Index were administered at baseline, mid-treatment (1 week after treatment start), and post-treatment.ResultsParticipants in the robot-assisted training group showed a significant improvement in the hemiplegia extremity, which was non-inferior to the enhanced upper extremity therapy group in FMA-UE (p < 0.05), while suggesting greater motor recovery of lower extremity in FMA-LE (p < 0.05) compared with the enhanced upper extremity therapy group. A marked increase in Modified Barthel Index was observed within groups; however, no significant difference was found between groups.ConclusionRobot-assisted training is non-inferior but not better in reducing impairment of the upper extremity and appears to be superior in reducing impairment of the lower extremity compared with enhanced upper extremity therapy for stroke survivors.LAY ABSTRACTAlthough post-stroke robot-assisted training of the upper extremity has been widely studied, its efficacy is not yet well defined, and its effects on the lower extremity are unknown. This study aimed to evaluate the effects of upper extremity robot-assisted training on the upper and lower extremities in stroke survivors. Robot-assisted training is non-inferior in improving the function of the upper extremity and superior in improving the function of the lower extremity compared with enhanced upper extremity therapy. Robot-assisted training can be used for functional recovery of the upper and lower extremities in stroke survivors.

AIMTo investigate non-ossifying fibromas (NOFs) common fibrous bone lesions in children that occur in bones of the lower extremities.METHODSWe analyzed 44 cases of NOF including 47 lesions, which were referred with a working diagnosis of neoplastic lesions. Lesions were located in the upper extremities (1 proximal humerus, 1 distal radius) and the lower extremities (25 distal femurs, 12 proximal and 4 distal tibias, and 4 proximal fibulas).RESULTSThree cases had NOFs in multiple anatomical locations (femur and fibula in 1 case, femur and tibia in 2 cases). Overall, larger lesions > 4 cm and lesion expansion at the cortex were seen in 21% and 32% of cases, respectively. Multiple lesions with bilateral symmetry in the lower extremities suggest that these NOFs were developmental bone defects. Two patients suffered from fracture and were treated without surgery, one in the radius and one in the femur. Lesions in the upper extremities (i.e., humerus of a 4-year-old female and radius of a 9-year-old male) expanded at the cortex and lesion size increased with slow ossification.CONCLUSIONNOFs in the lower extremity had fewer clinical problems, regardless of their size and expansiveness. In these two upper extremity cases, the NOFs had aggressive biological features. It seems that there is a site specific difference, especially between the upper extremity and the lower extremity. Furthermore, NOFs in the radius are predisposed to fracture because of the slender structure of the radius and the susceptibility to stress.

Trauma bypass performed by vascular surgeons demonstrate excellent long-term outcomes and limb preservation

Trauma Bypass Performed by Vascular Surgeons Demonstrate Excellent Long-term Outcomes and Limb Preservation

Reliability and Validity of a Low Load Endurance Strength Test for Upper and Lower Extremities in Patients With Fibromyalgia