Gut microbiome and inflammation among athletes in wheelchair in a crossover randomized pilot trial of probiotic and prebiotic interventions.

Disorders related to gut health are a significant cause of morbidity among athletes in wheelchair. This pilot feasibility trial aims to investigate whether probiotics compared to prebiotics can improve inflammatory status and gut microbiome composition in elite athletes in wheelchair. We conducted a 12-week, randomized, cross-over controlled trial involving 14 elite Swiss athletes in wheelchair. Participants were given a multispecies-multistrain probiotic or prebiotic (oat bran) daily for 4 weeks (Clinical trials.gov NCT04659408 09/12/2020). This was followed by a 4-week washout and then crossed over. Thirty inflammatory markers were assessed using bead-based multiplex immunoassays (LegendPlex) from serum samples. The gut microbiome was characterized via 16S rRNA sequencing of stool DNA samples. Statistical analyses were conducted using linear mixed-effect models (LMM). At baseline, most athletes (10/14) exhibited low levels of inflammation which associated with higher gut microbiome alpha diversity indices compared to those with high inflammation levels. The use of probiotic had higher decrease in 25 (83%) inflammatory markers measured compared to prebiotic use. Probiotic has the potential in lowering inflammation status and improving the gut microbiome diversity. The future trial should focus on having sufficient sample sizes, population with higher inflammation status, longer intervention exposure and use of differential abundance analysis.

Does cardiometabolic risk profile differ among individuals with traumatic and non-traumatic spinal cord injury (SCI): the evidence from the multicenter SCI cohort in Switzerland (SwiSCI).

STUDY DESIGN: Longitudinal study. OBJECTIVE: To explore whether individuals with traumatic spinal cord injury (TSCI) and non-traumatic SCI (NTSCI) experience different trajectories in changes of cardiometabolic disease (CMD) factors during initial rehabilitation stay. SETTING: Multicenter Swiss Spinal Cord Injury Cohort (SwiSCI) study. METHODS: Individuals without history of cardiovascular diseases were included. CMD factors and Framingham risk score (FRS) were compared between TSCI and NTSCI. Linear mixed models' analysis was employed to explore the trajectory in CMD factors changes over rehabilitation period and a multivariate linear regression analysis was used at discharge from inpatient rehabilitation to explore factors associated with CMD risk profile in TSCI and NTSCI. We performed age and sex-stratified analyses. RESULTS: We analyzed 530 individuals with SCI (64% with TSCI and 36% NTSCI). The median age was 53 years (IQR:39-64) with 67.9% (n = 363) of the study cohort being male. The median rehabilitation duration was 4.4 months (IQR 2.4-6.4). At admission to rehabilitation, FRS (9.61 vs. 5.89) and prevalence of hypertension (33.16% vs. 13.62%), diabetes (13.68% vs. 4.06%), and obesity (79.05% vs. 66.67%) were higher in NTSCI as compared to TSCI, No difference was observed in cardiometabolic syndrome between the groups (around 40% in both groups). Overall, we observed longitudinal increases in total cholesterol, HDL-C and HDL/total cholesterol ratio, and a decrease in fasting glucose over the rehabilitation period. No differences in longitudinal changes in cardiovascular risk factors were observed between TSCI and NTSCI. CONCLUSIONS: There was no deterioration in cardiometabolic risk factors over rehabilitation period, at discharge from initial rehabilitation stay. Both TSCI and NTSCI experienced high burden of cardiometabolic syndrome components with NTSCI experiencing more disadvantageous risk profile. The effectiveness of therapeutic and lifestyle/behavioral strategies to decrease burden of cardiometabolic disease and its components in early phase should be explored in future studies.

Optimized bacterial community characterization through full-length 16S rRNA gene sequencing utilizing MinION nanopore technology.

BACKGROUND: Accurate identification of bacterial communities is crucial for research applications, diagnostics, and clinical interventions. Although 16S ribosomal RNA (rRNA) gene sequencing is a widely employed technique for bacterial taxonomic classification, it often results in misclassified or unclassified bacterial taxa. This study sought to refine the full-length 16S rRNA gene sequencing protocol using the MinION sequencer, focusing on the V1-V9 regions. Our methodological enquiry examined several factors, including the number of PCR amplification cycles, choice of primers and Taq polymerase, and specific sequence databases and workflows employed. We used a microbial standard comprising eight bacterial strains (five gram-positive and three gram-negative) in known proportions as a validation control. RESULTS: Based on the MinION protocol, we employed the microbial standard as the DNA template for the 16S rRNA gene amplicon sequencing procedure. Our analysis showed that an elevated number of PCR amplification cycles introduced PCR bias, and the selection of Taq polymerase and primer sets significantly affected the subsequent analysis. Bacterial identification at genus level demonstrated Pearson correlation coefficients ranging from 0.73 to 0.79 when assessed using BugSeq, Kraken-Silva and EPI2ME-16S workflows. Notably, the EPI2ME-16S workflow exhibited the highest Pearson correlation with the microbial standard, minimised misclassification, and increased alignment accuracy. At the species taxonomic level, the BugSeq workflow was superior, with a Pearson correlation coefficient of 0.92. CONCLUSIONS: These findings emphasise the importance of careful selection of PCR settings and a well-structured analytical framework for 16S rRNA full-length gene sequencing. The results showed a robust correlation between the predicted and observed bacterial abundances at both the genus and species taxonomic levels, making these findings applicable across diverse research contexts and with clinical utility for reliable pathogen identification.

The Swiss Spinal Cord Injury Cohort Study (SwiSCI) biobank: from concept to reality.

OBJECTIVES: To describe the concept, establishment and the operationalization of the biobank of the Swiss Spinal Cord Injury Cohort Study (SwiSCI), the available biosamples, and demographic and clinical characteristics of study participants. SETTING: The SwiSCI biobank is a platform for research within SwiSCI. It collects and processes serum, plasma, PBMCs, RNA, DNA, and urine from three rehabilitation centers. Samples are collected at admission to first rehabilitation and at discharge. Additionly, the biobank provides services to projects nested in SwiSCI or otherclinical trials among Spinal Cord Injury population. METHODS: Descriptive statistics were used for an overview of available biosamples, study participant characteristics, and comparison of the participating centers. RESULTS: Between the SwiSCI biobank establishment on June 27th, 2016, and October 19th, 2023, the SwiSCI Study has obtained informed consent from 524 individuals. Of these, 315 (60.1%) have agreed to donate biospecimens to the biobank. The average age of the contributors was 54 years (range: 38-65), with the majority being male (80%). Most participants suffered from traumatic injuries (66%) and were classified as paraplegic (64%). Approximately 80% presented with motor and sensory-incomplete SCI. The median Spinal Cord Independence Measure (SCIM) score was 31 (Interquartile Range: 19-58). The proportion of individuals providing paired biosamples at two distinct time points ranged from 63% (for RNA) to 65% (for urine and urine sediment). CONCLUSIONS: The SwiSCI biobank is a unique platform designed to serve as a basis for collaborative SCI research, including multi-omics approaches. The longitudinal collection of biospecimens and cryopreservation of multiple aliquots for each participant are fundamental for scrutinizing the temporal associations, ensuring research reproducibility, and achieving an adequate sample size for future investigations.

Characteristics of the gut microbiome of Swiss elite athletes with a spinal cord injury: An exploratory study.

OBJECTIVES: To illustrate and explore associations between the gut microbiome and spinal cord injury (SCI) characteristics, physical training, dietary intake, body composition, and blood biomarkers of elite Swiss athletes. DESIGN AND SETTING: Baseline data analysis of athletes with SCI who participated in a pilot trial (NCT04659408) in the Swiss Paraplegic Center, Nottwil, Switzerland. PARTICIPANTS: Elite athletes, five males, and six females, with SCI who competed internationally. OUTCOME MEASURES: We conducted a differential abundance analysis and measured the alpha and beta diversity of the gut microbiome. RESULTS: The athletes' median age was 34.5 years. Six had traumatic SCI and five had a spina bifida. The athletes competed in para-cycling (5), wheelchair athletics (3), and wheelchair tennis (3). A higher duration of training per week was positively associated with Akkermansia and Akkermansiaceae but negatively associated with Prevotellaceae. Muribaculaceae was negatively associated with the average number of trainings per week. Waist circumference is negatively associated with Butyricimonas. Significant differences in the alpha diversity were found with sex, gastrointestinal quality of life index (GIQLI) scores, total caloric intake, total fat intake, total carbohydrate intake, and high-sensitivity C-reactive protein (hs-CRP). Beta diversity differences were found with impairment of the sympathetic nervous system of the gut at the genus level and HbA1c at the family level. CONCLUSIONS: This study provides insight into the gut microbiome of athletes with SCI. Our results were similar to those found in athletes without SCI. Further replication is needed to confirm the relationships of organisms observed in the gut of athletes with SCI.

Patent and Bibliometric Analysis of the Scientific Landscape of the Use of Pulse Oximeters and Their Prospects in the Field of Digital Medicine.

This study conducted a comprehensive patent and bibliometric analysis to elucidate the evolving scientific landscape surrounding the development and application of pulse oximeters, including in the field of digital medicine. Utilizing data from the Lens database for the period of 2000-2023, we identified the United States, China, the Republic of Korea, Japan, Canada, Australia, Taiwan, and the United Kingdom as the predominant countries in patent issuance for pulse oximeter technology. Our bibliometric analysis revealed a consistent temporal trend in both the volume of publications and citations, underscoring the growing importance of pulse oximeters in digitally-enabled medical practice. Using the VOSviewer software(version 1.6.18), we discerned six primary research clusters: (1) measurement accuracy; (2) integration with the Internet of Things; (3) applicability across diverse pathologies; (4) telemedicine and mobile applications; (5) artificial intelligence and deep learning; and (6) utilization in anesthesiology, resuscitation, and intensive care departments. The findings of this study indicate the prospects for leveraging digital technologies in the use of pulse oximetry in various fields of medicine, with implications for advancing the understanding, diagnosis, prevention, and treatment of cardio-respiratory pathologies. The conducted patent and bibliometric analysis allowed the identification of technical solutions to reduce the risks associated with pulse oximetry: improving precision and validity, technically improved clinical diagnostic use, and the use of machine learning.

Immune Status of Individuals with Traumatic Spinal Cord Injury: A Systematic Review and Meta-Analysis.

Individuals with spinal cord injury (SCI) have higher infection rates compared to those without SCI. In this review, the immune status difference between individuals with and without traumatic SCI is investigated by examining their peripheral immune cells and markers. PubMed, Cochrane, EMBASE, and Ovid MEDLINE were searched without language or date restrictions. Studies reporting peripheral immune markers' concentration and changes in functional capabilities of immune cells that compared individuals with and without SCI were included. Studies with participants with active infection, immune disease, and central nervous system (CNS) immune markers were excluded. The review followed the PRISMA guidelines. Effect estimates were measured by Weighted Mean Difference (WMD) using a random-effects model. Study quality was assessed using the National Heart, Lung, and Blood Institute Quality Assessment Tool. Fifty-four studies (1813 with SCI and 1378 without SCI) contributed to the meta-analysis. Leukocytes (n = 23, WMD 0.78, 95% CI 0.17; 1.38, I2 83%), neutrophils (n = 11, WMD 0.76, 95% CI 0.09; 1.42, I2 89%), C-reactive protein (CRP) (n = 12, WMD 2.25, 95% CI 1.14; 3.56, I2 95%), and IL6 (n = 13, WMD 2.33, 95% CI 1.20; 3.49, I2 97%) were higher in individuals with SCI vs. without SCI. Clinical factors (phase of injury, completeness of injury, sympathetic innervation impairment, age, sex) and study-related factors (sample size, study design, and serum vs. plasma) partially explained heterogeneity. Immune cells exhibited lower functional capability in individuals with SCI vs. those without SCI. Most studies (75.6%) had a moderate risk of bias. The immune status of individuals with SCI differs from those without SCI and is clinically influenced by the phase of injury, completeness of injury, sympathetic innervation impairment, age, and sex. These results provide information that is vital for monitoring and management strategies to effectively improve the immune status of individuals with SCI.

Patient safety discourse in a pandemic: a Twitter hashtag analysis study on #PatientSafety.

Background: The digitalization of medicine is becoming a transformative force in modern healthcare systems. This study aims to investigate discussions regarding patient safety, as well as summarize perceived approaches to mitigating risks of adverse events expressed through the #PatientSafety Twitter hashtag during the COVID-19 pandemic. Methods: This research is grounded in the analysis of data extracted from Twitter under the hashtag #PatientSafety between December 1, 2019 and February 1, 2023. Symplur Signals, which represents a tool offering a method to monitor tweets containing hashtags registered with the Symplur Healthcare Hashtag Project, was used for analyzing the tweets shared in the study period. For text analytics of the relevant data, we further used the word cloud generator MonkeyLearn, and VOSviewer. Results: The analysis encompasses 358'809 tweets that were shared by 90'079 Twitter users, generating a total of 1'183'384'757 impressions. Physicians contributed to 18.65% of all tweets, followed by other healthcare professionals (14.31%), and health-focused individuals (10.91%). Geographically, more than a third of tweets (60.90%) were published in the United States. Canada and India followed in second and third positions, respectively. Blocks of trending terms of greater interest to the global Twitter community within the hashtag #PatientSafety were determined to be: "Patient," "Practical doctors," and "Health Care Safety Management." The findings demonstrate the engagement of the Twitter community with COVID-19 and problems related to the training, experience of doctors and patients during a pandemic, communication, the vaccine safety and effectiveness, and potential use of off-label drugs. Noteworthy, in the field of pharmacovigilance, Twitter has the possibility of identifying adverse reactions associated with the use of drugs, including vaccines. The issue of medical errors has been also discussed by Twitter users using the hashtag #PatientSafety. Conclusion: It is clear that various stakeholders, including students, medical practitioners, health organizations, pharmaceutical companies, and regulatory bodies, leverage Twitter to rapidly exchange medical information, data on the disease symptoms, and the drug effects. Consequently, there is a need to further integrate Twitter-derived data into the operational routines of healthcare organizations.

Advancements in cell-based therapies for the treatment of pressure injuries: A systematic review of interventional studies.

The high recurrence and complications associated with severe pressure injuries (PI) necessitate the exploration of advanced treatments, such as cell-based therapies, to facilitate wound healing. Such techniques harness the ability of different cell types to promote angiogenesis, re-epithelialization of the skin, and tissue regeneration. This systematic review explores the efficacy of cell-based therapies and tissue engineering in treating deep PI. We searched for interventional studies using cells in the treatment of PI in adults in four online libraries (PubMed, Embase, Ovid Medline, and Cochrane; latest search 10th June 2023). We found one randomized clinical trial (RCT), two non-RCT, and three pre-post studies, comprising 481 study participants with PI (253 intervention/228 controls). The risk of bias was categorized as moderate due to minimal bias in outcome measurements, or high owing to unclear patient randomization methods, as assessed by the ROBINS-I, NIH, and RoB-2 tools. Four cell types were identified in the context of cell-based therapies of PI: bone marrow mononuclear stem cells (BM-MNCs, n = 2); hematopoietic derived stem cells (HSC, n = 1); macrophages and activated macrophage suspensions (AMS, n = 2); and cryopreserved placental membrane containing viable cells (vCPM, n = 1). Wound healing outcomes were observed in patients undergoing cell-based therapies, including complete wound closure (AMS, vCPM; n = 142), faster healing rate (BM-MNCs, AMS; n = 146), improved granulation tissue formation (HSC, n = 3) and shorter hospitalization time (BM-MNCs; n = 108) compared to standard of care, with no adverse reactions. PI healing rate decreased only in one study with BM-MNC therapy, compared to control (n = 86). Based on the available data, though with limited evidence, it seems that macrophage deployment showed the most favorable outcomes. The results indicate that cell-based therapies offer a potential avenue for enhancing wound healing and tissue repair in PI; however, more extensive research is needed in this domain.

Understanding the impact of spinal cord injury on the microbiota of healthy skin and pressure injuries.

Pressure injuries (PI) are a common issue among individuals with spinal cord injury (SCI), especially in the sitting areas of the body. Considering the risk of infections occurring to PI during the wound healing process, the skin microbiome is likely to be a source of bacteria. We investigated the relationship between skin and PI microbiomes, and assessed any correlation with clinically relevant outcomes related to PI. Samples were isolated from SCI patients undergoing reconstructive surgery of PI, severity grades III and IV. DNA samples from skin and PI were analysed using 16S rRNA gene sequencing. Our results showed disparities in microbiome composition between skin and PI. The skin had lower diversity, while PI showed increased bacterial homogeneity as the severity grade progressed. The skin bacterial composition varied based on its location, influenced by Cutibacterium. Compositional differences were identified between PI grades III and IV, with clusters of bacteria colonizing PI, characterized by Pseudomonas, Proteus and Peptoniphilus. The skin and PI microbiomes were not affected by the level of the SCI. Our study highlights the differences in the microbiome of skin and PI in SCI patients. These findings could be used to target specific bacteria for PI treatment in clinical practice.

Assessing the Feasibility of a Multimodal Approach to Pain Evaluation in Early Stages after Spinal Cord Injury.

This research evaluates the feasibility of a multimodal pain assessment protocol during rehabilitation following spinal cord injury (SCI). The protocol amalgamates clinical workup (CW), quantitative sensory testing (QST), and psychosocial factors (PSF) administered at 4 (T1), 12 (T2), and 24 (T3) weeks post injury and at discharge (T4). Molecular blood biomarkers (BB) were evaluated via gene expression and proteomic assays at T1 and T4. Different pain trajectories and temporal changes were identified using QST, with inflammation and pain-related biomarkers recorded. Higher concentrations of osteopontin and cystatin-C were found in SCI patients compared to healthy controls, indicating their potential as biomarkers. We observed altered inflammatory responses and a slight increase in ICAM-1 and CCL3 were noted, pointing towards changes in cellular adhesion linked with spinal injury and a possible connection with neuropathic pain. Despite a small patient sample hindering the correlation of feasibility data, descriptive statistical analyses were conducted on stress, depression, anxiety, quality of life, and pain interferences. The SCI Pain Instrument (SCIPI) was efficient in distinguishing between nociceptive and neuropathic pain, showing a progressive increase in severity over time. The findings emphasize the need for the careful consideration of recruitment setting and protocol adjustments to enhance the feasibility of multimodal pain evaluation studies post SCI. They also shed light on potential early adaptive mechanisms in SCI pathophysiology, warranting the further exploration of prognostic and preventive strategies for chronic pain in the SCI population.

The feasibility of a randomized controlled crossover trial to assess the effect of probiotic and prebiotic supplementation on the health of elite wheelchair athletes.

BACKGROUND: Gastrointestinal (GI) problems represent a health burden in Para athletes and can ultimately reduce athletic performance. This study aimed to evaluate the feasibility of a randomized controlled crossover trial (RCCT) assessing the effects of probiotic and prebiotic supplementation on the health of Swiss elite wheelchair athletes. METHODS: The RCCT was conducted between March 2021 and October 2021. Athletes were randomized to receive either a daily probiotic (3 g of probiotic preparation, including eight bacterial strains), or a daily prebiotic (5 g of oat bran) supplementation first. After the first supplementation phase (4 weeks), a washout period (4 weeks) and the second crossover supplementation phase (4 weeks) followed. Data were collected at four study visits (every 4 weeks) and included 3-day training and nutrition diaries, the Gastrointestinal Quality of Life Index (GIQLI) questionnaire, stool samples, and fasting blood samples. The study assessed the feasibility criteria such as recruitment rate, retention rate, success of data collection, adherence to the protocol, willingness to participate, and safety. RESULTS: This pilot study met the majority of the predefined minimum requirements for the feasibility criteria. Out of 43 invited elite wheelchair athletes, 14 (33%) consented (mean (standard deviation) age: 34 (9) years, eight females, 11 with a spinal cord injury). The desired sample size was not reached, but the achieved recruitment rate was modest, especially considering the population studied. All participating athletes completed the study. With the exception of one missing stool sample and two missing diaries, data were successfully collected for all athletes at all four visits. Most athletes adhered to the daily intake protocol for at least 80% of the days, both for probiotics (n = 12, 86%) and prebiotics (n = 11, 79%). Ten (71%) athletes would be willing to participate in a similar study again. No serious adverse events occurred. CONCLUSION: Despite the limited number of elite wheelchair athletes in Switzerland and the modest recruitment rate, the implementation of a RCCT in elite wheelchair athletes is feasible. The data collected in this study provide essential information for the design of the subsequent study which will include a larger cohort of physically active wheelchair users. TRIAL REGISTRATION: Swiss Ethics Committee for Northwest/Central Switzerland (EKNZ), 2020-02337). CLINICALTRIALS: gov, NCT04659408.

Energy Availability and Nutritional Intake during Different Training Phases of Wheelchair Athletes.

Optimizing nutritional intake and timing helps athletes to improve performance and long-term health. Different training phases can require varying nutritional needs. In this study, we conducted a descriptive assessment of dietary intake, energy availability (EA), and blood biochemical parameters in elite wheelchair athletes during distinct training phases. Data analyzed in this study were collected as part of a randomized controlled crossover trial exploring the feasibility of probiotics and prebiotic supplementation. Data were obtained from consecutive three-day diaries and blood samples, both collected at four different time points across four consecutive months. We included 14 athletes (mean (standard deviation) age 34 (9) years, eight females, and six males) active in different wheelchair sports. The mean daily nutritional intake (g/kg body mass) for females and males was 2.7 (0.9) and 4.0 (0.7) for carbohydrates, 1.1 (0.3) and 1.5 (0.3) for protein, and 0.8 (0.3) and 1.4 (0.2) for fat. EA did not change across the four time points in either female (p = 0.30) or male (p = 0.05) athletes. The mean EA was lower in female athletes compared to male athletes (p = 0.03). Low EA (≤30 kcal/ kg fat-free mass/day) was observed in female (58 (29) % of days) and male (34 (23) % of days) athletes. Iron deficiency with anemia was observed in two female athletes. Mean vitamin D levels were insufficient (<75 nmol/L). Macronutrient intake, EA, and blood biochemical parameters were suboptimal in this cohort of elite wheelchair athletes, especially in female athletes.

Burden of Cardiovascular Risk in Individuals With Spinal Cord Injury and Its Association With Rehabilitation Outcomes: Results From the Swiss Spinal Cord Injury Cohort.

OBJECTIVES: The aims of the study are to determine the cardiovascular risk burden rehabilitation discharge and to explore the association between recovery during rehabilitation and cardiovascular disease risk profile. METHODS: We included adults without cardiovascular disease admitted for rehabilitation. We evaluated rehabilitation outcomes on admission and discharge. Cardiovascular disease risk profile was assessed by Framingham risk score, high-density lipoprotein, and fasting glucose level. RESULTS: We analyzed data from 706 participants (69.6% men) with a median age of 53.5 yrs. The median time since injury was 14 days, and the admission length was 5.2 months. Majority had paraplegia (53.3%) and motor incomplete injury (53.7%). One third of the cohort had high cardiovascular risk profile before discharge. At discharge, poorer anthropometric measures were associated with higher Framingham risk score and lower high-density lipoprotein levels. Individuals with higher forced vital capacity (>2.72 l) and peak expiratory flow (>3.4 l/min) had 0.16 mmol/l and 0.14 mmol/l higher high-density lipoprotein compared with those with lower respiratory function, respectively. Individuals with higher mobility score (>12.5) and functional independence score (>74) had 0.21 and 0.18 mmol/l higher high-density lipoprotein compared with those with lower scores. CONCLUSIONS: There is high cardiometabolic syndrome burden and cardiovascular disease risk profile upon rehabilitation discharge. Higher respiratory function, mobility, and overall independence were associated with better cardiovascular disease risk profile, although with study design limitations and short follow-up. Future studies should explore whether rehabilitation outcomes could be used to prioritize screening. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon reading this journal article, the reader is expected to: (1) Determine the burden of cardiometabolic disease in the early phase of spinal cord injury (SCI); (2) Differentiate the proposed SCI cutoff for high-risk obesity from the able-bodied population; and (3) Increase physicians' acuity for detecting cardiometabolic disease in their practice. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Cardiometabolic risk profiling during spinal cord injury rehabilitation: A longitudinal analysis from the Swiss Spinal Cord Injury (SwiSCI) cohort.

BACKGROUND: Early screening is important in individuals with spinal cord injury (SCI) as they are deemed high risk for cardiometabolic diseases. Few studies explored changes in cardiometabolic risk profile in the early phase of the injury. Thus it remains unclear how early the cardiometabolic status deteriorates after injury. OBJECTIVE: To determine the longitudinal changes in the cardiometabolic risk profile and examine the association between injury characteristics and cardiometabolic status in subacute SCI. SETTING: Multicenter Swiss Spinal Cord Injury Cohort. PARTICIPANTS: Adults with traumatic SCI without a history of cardiovascular disease or type 2 diabetes. MAIN OUTCOME MEASURES: Blood pressure (BP), lipid profile, fasting glucose, waist circumference (WC), weight, body mass index (BMI), and Framingham risk score (FRS) were compared across time and according to the injury characteristics. RESULTS: We analyzed the data of 258 individuals with traumatic SCI (110 tetraplegia and 148 paraplegia, 122 motor complete, and 136 incomplete). The median age was 50 years (interquartile range [IQR] 32-60), with 76.4% (n = 197) of the population being male. The median rehabilitation duration was 5.5 months (IQR 3.2-7.1). At admission to rehabilitation, fully adjusted linear regression models showed higher baseline weight (ß 0.06, 95% confidence interval [CI] 0.005 to 0.11), systolic BP (ß 0.05, 95% CI 0.008 to 0.09), diastolic BP (ß 0.05, 95% CI 0.004 to 0.10), and triglycerides (ß 0.27, 95% CI 0.13 to 0.42) in paraplegia than tetraplegia. Systolic BP, diastolic BP, high-density lipoprotein cholesterol (HDL-C) levels were higher in incomplete than complete injury. In our main analysis, we observed an increase in cholesterol and HDL-C and lipid ratio when comparing the beginning and end of rehabilitation. Individuals with paraplegia had a higher increase in BMI than individuals with tetraplegia, whereas no differences in other cardiometabolic risk factors were detected when comparing motor incomplete and complete injury. Trajectories of each participant showed that the majority of individuals with SCI decreased FRS score at follow-up compared to baseline and no significant changes in the prevalence of cardiometabolic syndrome were observed. At discharge, one third of study participants were classified as moderate to high risk of cardiovascular disease (CVD), 64% were overweight, and 39.4% had cardiometabolic syndrome. CONCLUSION: We observed a modest improvement in lipid profile and FRS during the first inpatient rehabilitation hospitalization. Injury characteristics, such as level and completeness, were not associated with changes in cardiometabolic risk factors in the subacute phase of the injury. Despite this, a significant proportion of study participants remained at risk of cardiometabolic disease at discharge, suggesting that early cardiometabolic preventive strategies may be initiated as early as during the first inpatient rehabilitation hospitalization.

Early Changes in Androgen Levels in Individuals with Spinal Cord Injury: A Longitudinal SwiSCI Study.

We aimed to explore longitudinal changes in androgen levels in individuals with spinal cord injury (SCI) within initial inpatient rehabilitation stay and identify clinical/injury characteristics associated with hormone levels. Linear regression analysis was applied to explore the association between personal/injury characteristics and androgen hormones (total testosterone, free testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S)) at admission to rehabilitation. Longitudinal changes in androgen levels were studied using linear mixed models. Analyses were stratified by sex and by injury type. We included 70 men and 16 women with SCI. We observed a non-linear association between age, time since injury, and androgens at baseline. At admission to initial rehabilitation, mature serum SHBG (full-length, protein form which lacks the N-terminal signaling peptide) was higher, while DHEA and DHEA-S were lower among opioid users vs. non-users. Serum levels of total testosterone and DHEA-S increased over rehabilitation period [ß 3.96 (95%CI 1.37, 6.56), p = 0.003] and [ß 1.77 (95%CI 0.73, 2.81), p = 0.01], respectively. We observed no significant changes in other androgens. Restricting our analysis to men with traumatic injury did not materially change our findings. During first inpatient rehabilitation over a median follow up of 5.6 months, we observed an increase in total testosterone and DHEA-S in men with SCI. Future studies need to explore whether these hormonal changes influence neurological and functional recovery as well as metabolic parameters during initial rehabilitation stay.

Collaborative Challenges of Multi-Cohort Projects in Pharmacogenetics-Why Time Is Essential for Meaningful Collaborations.

Multi-cohort projects in medicine provide an opportunity to investigate scientific questions beyond the boundaries of a single institution and endeavor to increase the sample size for obtaining more reliable results. However, the complications of these kinds of collaborations arise during management, with many administrative hurdles. Hands-on approaches and lessons learned from previous collaborations provide solutions for optimized collaboration models. Here, we use our experience in running PGX-link, a Swiss multi-cohort project, to show the strategy we used to tackle different challenges from project setup to obtaining the relevant permits, including ethics approval. We set PGX-link in an international context because our struggles were similar to those encountered during the SYNCHROS (SYNergies for Cohorts in Health: integrating the ROle of all Stakeholders) project. We provide ad hoc solutions for cohorts, general project management strategies, and suggestions for unified protocols between cohorts that would ease current management hurdles. Project managers are not necessarily familiar with medical projects, and even if they are, they are not aware of the intricacies behind decision-making and consequently, of the time needed to set up multi-cohort collaborations. This paper is meant to be a brief overview of what we experienced with our multi-cohort project and provides the necessary practices for future managers.

Endocrinological and inflammatory markers in individuals with spinal cord injury: A systematic review and meta-analysis.

Spinal cord injury (SCI) can lead to dramatic physiological changes which can be a factor in developing secondary health conditions and might be reflected in biomarker changes in this elevated risk group. We focused specifically on the endocrine and inflammation profile differences between SCI and able-bodied individuals (ABI). Our aim was to determine the differences in inflammatory markers and endocrine profiles between SCI and ABI. We systematically searched 4 electronic databases for relevant studies. Human observational (cross-sectional, cohort, case-control) studies that compared biomarkers of interest between SCI and ABI population were included. Weighted mean difference between SCI and ABI was calculated using random-effects models. Heterogeneity was computed using I2 statistic and chi-squared test. Study quality was evaluated through the Newcastle-Ottawa Scale. The search strategy yielded a total of 2,603 studies from which 256 articles were selected for full-text assessment. Sixty-two studies were included in the meta-analysis. SCI individuals had higher levels of pro-inflammatory C-reactive protein and IL-6 than ABI. Creatinine and 25-hydroxyvitamin D3 levels were lower in SCI than ABI. Total testosterone levels and IGF-1 were also found to be lower, while cortisol and leptin levels were higher in SCI when compared to ABI. Accordingly, meta-regression, subgroup analysis, and leave-one-out analysis were performed, however, they were only able to partially explain the high levels of heterogeneity. Individuals with SCI show higher levels of inflammatory markers and present significant endocrinological changes when compared to ABI. Moreover, higher incidence of obesity, diabetes, osteoporosis, and hypogonadism in SCI individuals, together with decreased creatinine levels reflect some of the readily measurable aspects of the phenotype changes in the SCI group. These findings need to be considered in anticipating medically related complications and personalizing SCI medical care.

The feasibility of a crossover, randomized controlled trial design to assess the effect of probiotics and prebiotics on health of elite Swiss para-athletes: a study protocol.

BACKGROUND: Spinal cord injury (SCI) may cause an autonomic imbalance in the gastrointestinal tract, leading to deficits in colonic motility, mucosal secretions, vascular tone, and an increase of intestinal barrier permeability. Autonomic denervation and factors such as age, physical activity, antibiotic use and stress may cause intestinal bacterial translocation, decreased microbiota diversity, known as gut dysbiosis and thus increase susceptibility to experiencing gastrointestinal discomfort. Probiotic treatment in individuals with SCI may normalize the gut microbiota and improve overall health. We aim to assess the feasibility of probiotic and prebiotic intervention in athletes with SCI and collect information necessary for sample size calculation of a definite trial on improving health outcomes in para-athletes. METHODS AND ANALYSIS: Elite Swiss para-athletes (aged> 18 years), being shortlisted for the Paralympic Games 2021 in Tokyo or a member of a national team (n = 43), will be invited to participate in this single-center randomized crossover trial. Athletes suffering from chronic inflammatory bowel diseases, those currently taking antibiotics or other medication to alleviate gastro-intestinal complaints will not be eligible to be included in the study. Athletes will be randomized (1:1) to receive for 4 weeks a daily dose of either 3 g of probiotic preparation or 5 g of prebiotic (organic oat bran) supplementation in addition to usual diet, followed by a 4-week washout period or vice versa. The primary outcome is the feasibility of the study, measured by recruitment and dropout rates, feasibility of the measurements, acceptability and adherence to the intervention. Secondary outcomes include gastrointestinal health assessment, diet and training information, handgrip strength, blood diagnostic parameters, and intestinal microbiome characterization. The changes in clinically relevant secondary outcome values will be used to make a power calculation for definite trial. DISCUSSION: This pilot trial will address two common challenges in SCI research: the difficulty to recruit enough participants for a sufficiently powered study and the ability to collect data within the limits of a realistic budget and time frame. Upon demonstrated feasibility of the intervention and study procedures, the intervention will be evaluated in a definitive controlled trial comprising a larger sample of para-athletes (elite, engaged, or recreationally active) individuals with a SCI. TRIAL REGISTRATION: NCT04659408.

Physical activity and cardiometabolic risk factors in individuals with spinal cord injury: a systematic review and meta-analysis.

Physical inactivity in individuals with spinal cord injury (SCI) has been suggested to be an important determinant of increased cardiometabolic disease (CMD) risk. However, it remains unclear whether physically active SCI individuals as compared to inactive or less active individuals have truly better cardiometabolic risk profile. We aimed to systematically review and quantify the association between engagement in regular physical activity and/or exercise interventions and CMD risk factors in individuals with SCI. Four medical databases were searched and studies were included if they were clinical trials or observational studies conducted in adult individuals with SCI and provided information of interest. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the certainty of evidence. Of 5816 unique citations, 11 randomized clinical trials, 3 non-randomized trial and 32 cross-sectional studies comprising more than 5500 SCI individuals were included in the systematic review. In meta-analysis of RCTs and based on evidence of moderate certainty, physical activity in comparison to control intervention was associated with: (i) better glucose homeostasis profile [WMD of glucose, insulin and Assessment of Insulin Resistance (HOMA-IR) were - 3.26 mg/dl (95% CI - 5.12 to - 1.39), - 3.19 µU/ml (95% CI - 3.96 to - 2.43)] and - 0.47 (95% CI - 0.60 to - 0.35), respectively], and (ii) improved cardiorespiratory fitness [WMD of relative and absolute oxygen uptake relative (VO2) were 4.53 ml/kg/min (95% CI 3.11, 5.96) and 0.26 L/min (95% CI 0.21, 0.32) respectively]. No differences were observed in blood pressure, heart rate and lipids (based on evidence of low/moderate certainty). In meta-analysis of cross-sectional studies and based on the evidence of very low to low certainty, glucose [WMD - 3.25 mg/dl (95% CI - 5.36, - 1.14)], insulin [- 2.12 µU/ml (95% CI - 4.21 to - 0.03)] and total cholesterol [WMD - 6.72 mg/dl (95% CI - 13.09, - 0.34)] were lower and HDL [WMD 3.86 mg/dl (95% CI 0.66, 7.05)] and catalase [0.07 UgHb-1 (95% CI 0.03, 0.11)] were higher in physically active SCI individuals in comparison to reference groups. Based on limited number of cross-sectional studies, better parameters of systolic and diastolic cardiac function and lower carotid intima media thickness were found in physically active groups. Methodologically sound clinical trials and prospective observational studies are required to further elaborate the impact of different physical activity prescriptions alone or in combination with other life-style interventions on CMD risk factors in SCI individuals.