Immunomodulation for primary prevention of urinary tract infections in patients with spinal cord injury during primary rehabilitation: protocol for a randomized placebo-controlled pilot trial (UROVAXOM-pilot).

BACKGROUND Urinary tract infections (UTIs) are common in individuals with neurogenic lower urinary tract dysfunction (NLUTD) following spinal cord injury (SCI). They are not only a great burden for affected individuals, but also cause considerable health costs. Furthermore, recurrent antibiotic treatments of UTIs contribute to the growing problem of bacterial resistance to antimicrobial compounds. Even though there is a multitude of different measures to prevent UTIs in individuals with NLUTD, no clear evidence exists for any of these. Oral immunomodulation with UTI-relevant Escherichia coli lysate may be a promising preventative measure with a good safety profile in individuals with NLUTD. However, currently available data are sparse. METHODS This is a randomized, quasi-blinded, placebo-controlled, mono-centric pilot trial investigating the feasibility of a main trial regarding the effects of a lyophilized lysate of E. coli strains for oral application (Uro-Vaxom®, OM Pharma SA, Meyrin, Switzerland). There will be two parallel groups of 12 participants each. Individuals with acute SCI (duration SCI ≤ 56 days) from 18 to 70 years of age admitted for primary rehabilitation will be eligible. Blood and urine samples will be taken prior to intervention start, at the end of the intervention, and 3 months after intervention termination. The trial intervention will last 90 days. The participants will not be informed regarding the treatment allocation (quasi-blinded). The nursing staff will prepare the daily dose of the allocated treatment from the original packaging. The trial personnel and the biostatistician will be blinded. Feasibility (e.g., recruitment rate, patient attrition), clinical (e.g., number of symptomatic UTIs), and laboratory parameters (e.g., urinary culture, urinary proteo- and microbiome, blood cell counts) as well as adverse events will be collected. DISCUSSION Effective and efficient measures for the prevention of UTIs in individuals with NLUTD are urgently needed. If the conclusion of this pilot is positive regarding feasibility, the effects of oral immunomodulation with a E. coli lysate will be investigated in a larger, sufficiently powered, multi-center trial. TRIAL REGISTRATION ClinicalTrials.gov NCT04049994 . Registered on 8 August 2019

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

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

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

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

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

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

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

Acceptability of the dengue vaccination among parents in urban poor communities of Quezon City, Philippines before and after vaccine suspension

Abstract Objective The study aims to illustrate the acceptability of the dengue vaccine before and after the dengue vaccination suspension in urban poor communities in Quezon City, Philippines. Results There were 12 interviews conducted in November 2017 and 5 focus group discussions in January 2018, a month after vaccine program suspension with 41 participants. All participants were selected through purposive criterion sampling. Thematic analysis showed acceptability of the dengue vaccine was associated with parental experience with vaccination and dengue, trust in public health institutions and communication received by parents. Post-dengue vaccination suspension triangulation indicated that the parents regretted the experience, trust to public institutions was eroded and the communication strategy was deemed inadequate. This led to low vaccine acceptability post-vaccine suspension