2 Minute Medicine Rewind September 9, 2024
Exoskeletal-Assisted Walking in Veterans With Paralysis
1. In veterans with spinal cord injuries, exoskeletons showed no clear benefits (medical, physical or psychological) compared to standard wheelchair use
2. Exoskeleton technology is still not adopted readily with participants only using the devices an average of 86 minutes per week
Evidence Rating Level: 1 (Excellent)
Spinal cord injuries (SCI) often result in severe walking limitations which lead to various degrees of permanent disabilities. Walking strategies post-SCI have included leg bracing or functional electrical stimulation with crutches or a walker. These methods are highly energy intensive and have minimal long-term adoption. Exoskeletal devices are an energy-efficient solution to support walking in patients with SCI. They are made of motors at the hip and knees, supportive balance devices, and computer algorithms. The safety and efficacy of exoskeletal-assisted walking (EAW) has yet to be studied which was the reason for this randomized clinical trial. Participants were randomized to receive standard care (wheelchair use) or an FDA-cleared exoskeletal EAW device for 4 months. Satisfaction with either modality was measured using the 36-Item Health Survey (MCS/VR-36) and the Spinal Cord Injury-Quality of Life (SCI-QOL) physical and health domain. The primary outcome measurement for “improvement” in either score was a 4.0 increase in the MCS/VR-36 and 10% improvement in the total T score of the SCI-QOL. Within the 161 included participants, there was no significant difference in the proportion of participants who noted an improvement. The only significant difference seen between the two groups was the EAW group noted a significant reduction in sleep disturbance relative to the control group except at the final time point (4 months) where there was no significant difference. No other significant differences were seen in either the SCI Functional Index, SCI-QOL emotional health domain, nor the SCI-QOL social participation domain. The main reasons noted for not using the exoskeleton included companion unavailability (43.9%), illness (17.4%), being busy (14.4%), travel (9.2%), and weather (6.0%). Overall, no clinically meaningful changes in mental, physical, or medical well-being were seen. This could have been due to the low usage of the devices (86 minutes per week) which might not be enough to elicit meaningful changes for patients. To improve devices in the future, increasing usability (donning and doffing, self-balancing technology, etc.) could lead to increased adaptation of the technology.
Plasma Biomarkers of Traumatic Brain Injury in Adolescents With Sport-Related Concussion
1. GFAP, UCH-L1, NfL, and t-tau are all promising plasma biomarkers that show sex specific changes in adolescents post sport-related concussion.
2. GFAP and NfL show positive associations with symptom totals and severity whereas t-tau shows negative associations initially post-injury (10 days) and then shows a positive association
Evidence Rating Level: 2 (Good)
Sport-related concussion (SRC) in adolescent population is an important area of research as rates of substantial impact of prolonged symptoms have increased in recent years. The developing brain is also more vulnerable to injury, further increasing the importance of injury identification. Diagnosis of SRC has no current gold standard, instead relying on subjective clinical examination where non-specific symptoms must be interpreted. An objective measure of SRC, such as blood-based biomarkers, could help solve this issue. Current research shows promising candidates for central nervous system (CNS) injury following SRC. These include glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase-L1 (UCH-L1), neurofilament light (NfL), and possibly total tau (t-tau). These findings have yet to be verified in an adolescent population. Therefore, this study aimed to identify blood-based biomarkers in adolescents with SRC. 1023 plasma samples from 695 uninjured and 154 concussed adolescents were collected and analyzed for presence of GFAP, UCH-L1, NfL, and t-tau. Samples were collected whenever possible and grouped into post-injury day (PID) 0-3, 4-10, 11-28, and >28. GFAP analysis showed sex-specific differences post-SRC. Post-SRC females had significantly higher GFAP in the acute and subacute phases of recovery (p=0.001 and p=0.02 respectively) but not past PID 28. Males however had higher GFAP at all time points. GFAP increases were also 5.4% less likely per year as age increased (p<0.001). UCH-L1 was increased in females post-SRC at all time points (p=0.003, p=0.03, p=0.002, and p<0.001 respectively). No significant changes were seen in males. NfL only showed significant changes in males comparing uninjured and PID 0-3 days. No changes in females were seen. Finally, t-tau showed lower t-tau in all post-SRC time points compared to uninjured levels. For males, lower t-tau levels were seen from PID 1-10 and higher t-tau levels from days 11-28. When comparing the biomarkers to symptoms, GFAP and NfL were positively associated with symptom total and severity whereas t-tau was negatively associated with symptom total and severity for the first 10 days then was positively associated. The key limitation of the study would be the lack of samples from uninjured individuals who later experienced SRC as well as later timepoints that could show biomarker changes throughout recovery.
Quantitative sensory testing and chronic pain syndromes: a cross-sectional study from TwinsUK
1. Chronic pain syndromes including fibromyalgia, dry eye disease, and irritable bowel syndrome showed no significant association with quantitative sensory testing modalities or inflammatory markers
Evidence Rating Level: 3 (Average)
Chronic pain is a widespread and highly heterogenous group if diseases that requires a method of pain phenotyping and measurement. Chronic pain syndromes (CPS) are a cluster of conditions including fibromyalgia, dry eye disease (DED), and irritable bowel syndrome (IBS). CPS show genetic and symptomology overlap in the TwinsUK cohort. Quantitative sensory testing (QST) is composed of psychophysical tests that assess perceptions caused by various sensory stimuli including thermal and mechanical stimuli at various intensities. QST has been validated in grading neuropathic pain but has not been readily adopted for chronic pain groups. Another strategy to quantify pain is the use of inflammatory markers. This cross-sectional study aimed to determine if QST and inflammatory markers can be used as phenotyping tools for CPS. 10 QST modalities were administered, and scores were compared between participants with fibromyalgia and those without. Similarly, DED and IBS patients were compared to controls. No significant differences were seen between patients with fibromyalgia, DED, or IBS compared to controls in any of the 10 QST modalities. Inflammatory markers investigated were determined a priori and included interleukin-6 (IL-6), IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor (TNF). After correction for age, BMI, and twin relatedness, no significant associations were found between fibromyalgia, DED, or IBS. In a mixed effects logistic regression, IBS was associated with IL-8 (p=0.036). As the first large-scale investigation into QST modalities in CPS, no true associations were seen. Additionally, the examined inflammatory markers were also candidate inflammatory markers for CPS.
1. Patients with HIV treated with ART have a 31.5% chance of being anemic with many significantly positively associated risk factors that can be easily screened for and monitored
Evidence Rating Level: 3 (Average)
Anemia is a significant cause of morbidity and mortality in individuals undergoing highly active antiretroviral therapy (HAART). An estimate showed 46.60% of all individuals living with HIV on HAART experience anemia with 1/3 North American patients having anemia. The aim of this retrospective cross-sectional study was to look at the prevalence of anemia in patients receiving HAART and more specifically tenofovir (TDF), lamivudine (3TC) or dolutegravir (TLD) as they were being rolled out as first-line therapy in Ethiopia. HIV-reactive adults (aged ≥18 years) on HAART (≥6 months) with complete information were enrolled. Patients with blood disorders, pregnant women, or women in the postpartum period (within 6 weeks of giving birth) were excluded from the study. Of the included participants, 31.5% were anemic with 2.2% having severe anemia. Using bivariate logistic regression analysis, many characteristics were positively associated anemia including age >40 years old, female sex, illiteracy, 6-10 years and >10 years lived with HIV, CD4+ T-lymphocyte count <200 cells/µL, and >10 years on ART. A multivariate binary logistic regression analysis showed >40 years old, female sex, >10 years lived with HIV, CD4+ T-lymphocyte count <200 cells/µL, and positive history of opportunistic infections as significantly positively associated factors. Therefore, when treating patients with HIV with tenofovir, lamivudine or dolutegravir, extra attention should be paid to the possibility of anemia in these patients. Socioeconomic factors should also be taken into account as factors such as primary schooling and illiteracy are significantly associated with anemia in HIV patients.
Impact of different visceral metastatic sites on survival in metastatic prostate cancer patients
1. In a retrospective analysis of 59,875 patients with metastatic prostate cancer, varying prognoses were found primarily depending on the site of metastasis
2. Asian patients had the best overall prognosis followed by African American and finally Caucasian patients
Evidence Rating Level: 3 (Average)
Prostate cancer is the fourth most diagnosed cancer in men and eight leading cause of cancer death worldwide. Localized prostate cancer has good survival outcomes, however, metastatic prostate cancer (mPC) confers a high risk of death. However, the effect on prognosis of the metastatic site has not yet been adequately studied. This retrospective analysis of the TriNetX database investigated the influence of different visceral metastatic sites on the prognosis of patients with prostate cancer. A total of 59,875 patients with metastatic prostate cancer were identified with 39,495 (65.2%) having bone metastases, 7,573 (12.5%) with lung only visceral metastases, 5,240 (8.7%) with brain only visceral metastases, and 7,567 (12.5%) with liver only visceral metastases. The median overall survival (OS) was 15.7 months. The longest median OS was for bone metastases at 44.4 months followed by lung metastases at 31.9 months. Brain and liver metastases had drastically lower median OS at 9.6 months and 10 months respectively. No statistical difference in OS were seen between brain and liver metastases but both experienced poorer prognosis relative to lung metastases. When patients had two visceral metastatic sites, the median OS was 8 months for liver and lung metastases. Liver and lung metastases had a median OS of 6.6 months. Liver and brain metastases had the lowest median OS at 3.1 months. Liver and brain metastases patients had a significantly lower median OS compared to liver and lung metastases (p<0.0001). Brain and lung metastases patients had a significantly higher median OS compared to liver and lung metastases patients (p<0.0001). In mPC patients with concomitant visceral and bone metastases, the median OS was 17 months with the worst prognosis being liver and bonee metastases (5.4 months, p<0.0001). In mPC with visceral metastases and concomitant lymph node metastases, the median OS was 42.2 months with the worst prognosis occurring in patients with no significant difference between brain + lymph node and liver + lymph node metastases. Patients with mPC with visceral metastases and concomitant bone and lymp node metastases, median OS were lower at 15 months. Patients with liver, bone, and lymph node metastases experienced thee worst survival outcome at 5.6 months (p = 0.004). When accounting for the race of patients, Asian patients had the highest survival followed by African American, and finally Caucasian patients.
Image: PD
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