High Responders Research Articles

P1333 Trajectory analyses to optimise third booster COVID-19 vaccination in patients with Inflammatory Bowel Disease: final analyses of the J-COMBAT trial

Abstract Background Even after resolving pandemic, the verification of COVID-19 vaccination is important to optimise vaccination against next crisis.1,2 Methods Data at 39 institutes were prospectively acquired at eight predetermined timepoints before and after three manufacturers’ recommended vaccine doses including 3rd booster vaccination in a multicentre observational controlled study (UMIN000043545).3 Blood sample collections to measure anti-SARS-CoV-2 spike IgG antibody titers were planned prior to each vaccination, and at 4 weeks, 3 months and 6 months post-2nd and 3rd vaccination. We performed trajectory analysis to identify the degree of immune response and associated factors including baseline characteristics and immunomodulatory drug treatments in IBD patients compared with controls. Results Overall, 679 IBD patients and 203 controls were enrolled, and 473 IBD patients who were treated with immunomodulatory drugs that were well-balanced for each mode of action and 169 controls were analysed through three vaccine doses. 63 IBD patients and 16 controls affected by COVID-19 breakthrough infection. Trajectory analyses indicated four distinct patterns of change in immune response to 3rd vaccination in IBD patients: high (4.9%), moderately high (52.3%), moderately low (36.9%) and low responders (5.9%), and none stepped up the degree from low (Figure). Older age, anti-TNFα (odds ratio, 0.16; 95% CI, 0.06-0.45) and combined with thiopurine (0.02; 0-0.22) were negative factors associated with high response (Table). Combined anti-TNFα and thiopurine (p<0.001), and tofacitinib (p<0.001) was significantly associated with a different trajectory pattern from the control. Among each drug, only tofacitinib (fold change relative to the control 0.4, 0.21-0.76; p=0.005) was significantly associated with weakened elevation of the antibody titer at 4 weeks post-3rd vaccination referred to pre-3rd vaccination. Compared to 2nd vaccination, this relative suppression of immune response in other immunomodulatory drugs shrank 0.32 to 0.62 in patients treated with anti-TNFα with thiopurines, and 0.69 to 0.88 with systemic steroids. 15.4 % of breakthrough-infected IBD patients were infected at the status less than fourfold rise of genomic mean titer (GMT), especially half of them (7.7%) were infected at the status of almost negative GMT. Moreover, 27.8% of infected IBD patients didn’t show the increasing GMT after breakthrough infection. Conclusion Assessment of changes over time is essential to optimise COVID-19 vaccination, especially in low responders. Additional booster vaccination should be considered for these low responders. Trajectory analysis is a useful approach to identify the degree of immune response sufficiency according to individual differences.

P0115 Selective immune responses to Lachnospiraceae flagellins discriminate therapy-naive pediatric Crohn’s disease patients with distinct host-microbial interaction

Abstract Background Pathogenic CD4+ T-cell responses to commensal microbial antigens drive intestinal inflammation in Crohn’s disease (CD). Both hypo- or hyperactive anti-microbial innate immunity could underlie these aberrant T-cell responses. CD patients have increased IgG and T cell responses against commensal Lachnospiraceae-derived flagellins, which associate with disease complications. We investigated whether CD patients with high anti-Lachnospiraceae flagellin responses at diagnosis have underlying innate hypo- or hyperresponsiveness and high IgG responses to other dysbiotic commensals. Methods IgG reactivity to 19 recombinant flagellins from Lachnospiraceae species colonizing mouse and human gut, was measured in plasma of therapy-naïve pediatric CD patients (n=49) and controls (n=29). In addition, we measured plasma IgG responses to 1 recombinant flagellin and 71 microbial lysates of dysbiotic commensal species in therapy-naive pediatric CD patients (n=103) and controls (n=61). IgG responses were related to immunological and clinicopathological parameters. Results CD patients had significantly higher IgG responses to 12/19 Lachnospiraceae-derived flagellins compared to controls. Multi-reactivity to more than 10 flagellins was common in CD (41%) and associated with increased circulating flagellin-specific memory CD4+ T-cell frequencies. Multi-reactivity, and even single-reactivity to recombinant flagellin, correlated with reduced immune cell infiltration and epithelial damage, and fewer calprotectin-positive neutrophils in colonic lesional tissue, based on histological severity scoring and immune histochemistry, respectively. As these data may argue that high anti-flagellin IgG reactivity relates to innate hyporesponsiveness, we next assessed whether patients had a generalized high IgG response to lysates of dysbiotic intestinal bacteria. Hierarchical clustering identified subgroups of CD patients with different patterns of significantly increased anti-commensal IgG responses. Patients with high anti-Lachnospiraceae flagellin IgG also had high IgG responses against lysate of Roseburia inulinivorans, a Lachnospiraceae species. Of these anti-flagellin high responders, two-thirds responded to many commensals while one-third did not, arguing against a generalized high anti-commensal IgG response. Conclusion In conclusion, high IgG responses to Lachnospiraceae-derived flagellins identify a subgroup of pediatric therapy-naive CD patients with features of innate hyporesponsiveness. These patients do not have uniformly high IgG responses to other dysbiotic commensals, arguing that disturbed host-microbiota responses in CD are highly personalized and do not stem from an overall failure in microbiota-host crosstalk.

Dual Trigger in IVF—A SWOT Analysis

The typical agent used for final oocyte maturation and resumption of meiosis in in-vitro fertilisation (IVF) has been human chorionic gonadotropin (hCG). This acts as a surrogate for the physiological spontaneous luteinising hormone (LH) surge. Gonadotropin-releasing hormone agonist (GnRH-a) has been used as an alternative trigger in cycles where endogenous LH control is achieved using GnRH-antagonist and has been shown to be an effective method of reducing the risk of OHSS. However, GnRHa trigger is associated with poor corpus luteum function, leading to impaired endometrial receptivity. A combination of a GnRHa and hCG (dual trigger) was proposed to improve IVF cycle outcomes, especially in poor and normo-responder patients. Dual trigger aims to provide a more physiological alternative to HCG-only trigger while obviating some of the problems associated with GnRHa alone. Clinical evidence now supports the value of dual trigger where there has been a previous low proportion of mature eggs or where there is a suboptimal LH response to GnRHa alone. In poor responders, dual triggers could be considered as an effective first line. Dual trigger allows for comparable outcomes in normal and high responders, allowing the possibility of fresh embryo transfer with good clinical pregnancy and live birth rates while minimising OHSS risk.

Patterns of Weight Change Trajectories and Treatment Response in an Integrated Adult Primary Care Weight Management Practice.

Given the significant interindividual variable responses to interventions for obesity, the early identification of factors associated with a differential in weight loss would benefit real-world approaches in clinical practice. This study evaluated the factors associated with individual variability in response to enrolling in a weight management program integrated into an academic-based primary care practice. Data were retrospectively collected and analyzed for patients referred to a primary care-based weight management practice between 2012 and 2020. A mixed-model, semi-parametric group-based modeling approach was used to identify group membership and explore weight change trajectories over 18months, as measured by the percent of initial body weight loss and the probability of losing at least 5% of initial body weight (IBW). Three hundred ninety-three patients were included in the study; the median age was 53years, 84% female, 40% self-identified as non-Hispanic Black, and about one-third white. Among those, 374 had sufficient follow-up data for group-based modeling. Four groups were identified and named: "Weight Gainers" added 1.3% of IBW; "Initial Resistors" lost 6.7% of IBW; "Early Maintainers" lost 7.1% of IBW; and "Steady Achievers" lost 15% of IBW. Weight change in all groups was over 18months. The probability of losing 5% IBW was described by three groups: "Minimal Late Responders," "Moderate Responders," and "High Early Responders." Younger age, non-Hispanic Black race, fewer follow-up visits, and lower proportion prescribed two or more anti-obesity medications (AOMs) simultaneously were associated with a lower probability of achieving 5% IBW. Compared to the other groups, Weight Gainers and Minimal Late Responders had a distinct trajectory associated with two modifiable factors: the number of treatment visits and AOMs. Tailored interventions targeting these factors early may increase the probability of meaningful weight loss.

Variability in Vaccine Response and Trajectory in Early Childhood and Association with Demographic Variables, Antibiotic Exposure and Infection Proneness.

We sought to explore the variability of antibody responses to multiple vaccines during early life in individual children, assess the trajectory of each child longitudinally, determine the associations of demographic variables and antibiotic exposures with vaccine-induced immunity, and link vaccine responsiveness to infection proneness. In 357 prospectively-recruited children, age six through 36 months, antibody levels to 13 routine vaccine antigens were measured in sera at multiple time points and normalized to their respective protective thresholds to categorize children into four groups: very low, low, normal, and high vaccine responder. Demographic variables and frequency of antibiotic exposure data were collected. Participants were followed to determine change in vaccine groups over time and occurrences of infections. Vaccine-induced antibody levels persisted over time as very low, low, normal, or high in individual children and changed post-primary through post-booster immunizations against multiple antigen types, including toxoids, purified proteins, polysaccharide-protein conjugates, recombinant proteins and inactivated viruses. Factors influencing persistence or change in vaccine response group were assessed. Children who did not attend day care and African American/multiracial children had higher vaccine-induced antibody levels than White children. Children with lower vaccine-induced antibody levels had more frequent antibiotic exposures. Low vaccine responsiveness was linked to more frequent antibiotic-treated bacterial infections. When vaccine-induced antibody levels are used to define vaccine response groups, individual children may persist or change groups over time, which is associated with demographic variables and influenced by antibiotic exposures. Lower vaccine responsiveness can be linked to more frequent antibiotic-treated bacterial infections.

Are Vocational High School Students Ready for Global Competitiveness?: Self-Perception on Their English Proficiency

The study investigates the English proficiency of vocational high school students in Surabaya, East Java, Indonesia, employing a descriptive qualitative method and survey research design. With a total of 472 respondents from five public vocational high schools, the study reveals a predominant focus on Class XII students (99.6%), indicative of readiness for career pursuits or higher education. Notably, 60% major in social science and 40% in technological science. A crucial aspect of the research lies in its exploration of the self-perception of English proficiency among respondents, where findings indicate that 68.6% perceive speaking as their weakest skill, followed by writing (7%), reading (8.1%), and listening (16.3%). The analysis underscores the pronounced inadequacy in speaking proficiency among vocational high school students in Surabaya, East Java, Indonesia, a critical skill for global competitiveness in today's interconnected job market. Addressing these deficiencies is imperative to prepare vocational high school respondents, for global competitiveness, aligning with insights regarding the integration of speaking activities to enhance communication skills.

Differences in eHealth Access, Use, and Perceived Benefit Between Different Socioeconomic Groups in the Dutch Context: Secondary Cross-Sectional Study.

There is a growing concern that digital health care may exacerbate existing health disparities. Digital health care or eHealth encompasses the digital apps that are used in health care. Differences in access, use, and perceived benefits of digital technology among socioeconomic groups are commonly referred to as the digital divide. Current research shows that people in lower socioeconomic positions (SEPs) use eHealth less frequently. This study aims to (1) investigate the association between SEP and eHealth access to, use of, and perceived benefit within the adult Dutch population and (2) evaluate disparities in eHealth access, use, and perceived benefit through three socioeconomic variables-education, standardized income, and the socioeconomic status of the neighborhood. A secondary analysis was conducted on data from the Nivel Dutch Health Care Consumer Panel (response rate 57%, 849/1500, to assess access to, use of, and perceived benefits from eHealth. These data were collected to monitor eHealth developments in the Netherlands. eHealth was examined through two concepts: (1) eHealth in general and (2) websites, apps, and wearables. Results were stratified into 9 SEP populations based on 3 indicators-education, standardized income, and socioeconomic status level of the neighborhood. Logistic regression analyses were performed to evaluate whether the outcomes varied significantly across different SEP groups. Age was included as a covariate to control for confounding. This study confirms the association between eHealth and SEP and shows that low SEP respondents have less access (odds ratio [OR] 5.72, 95% CI 3.06-10.72) and use (OR 4.96, 95% CI 2.66-9.24) of eHealth compared to medium or high SEP respondents. Differences were most profound when stratifying for levels of education. The access to and use of eHealth has a socioeconomic gradient and emphasizes that SEP indicators cannot be used interchangeably to assess eHealth access and use. The results underline the importance of activities and policies aimed at improving eHealth accessibility and usage among low SEP groups to mitigate disparities in health between different socioeconomic groups.

INCIDENCE OF STEROID-RELATED OCULAR HYPERTENSION AND CATARACT FORMATION AFTER SUB-TENON TRIAMCINOLONE IN NONUVEITIC PEDIATRIC PATIENTS.

To describe intraocular pressure changes after injection of sub-Tenon triamcinolone during examination under anesthesia for pediatric patients. Multicenter, retrospective case series of pediatric patients who received sub-Tenon triamcinolone from three tertiary care ophthalmic services between November 2018 and October 2023. Of 392 patients identified, 59 eyes (10.5%) of 41 patients were included. Laser was administered in 95.1% of the cases. Sub-Tenon triamcinolone dose ranged from 4 to 20 mg. The most common diagnosis was retinopathy of prematurity (43.9%). Two eyes (3.4%) of two patients (4.9%) were mild steroid responders. One eye (1.7%) of 1 patient (2.4%) was a moderate responder. There were no high steroid responders, and all eyes with steroid response showed a return of intraocular pressure to normal range at next visit without needing any intraocular pressure-lowering medications. No patients were diagnosed with glaucoma or required glaucoma surgery. Only 1 eye (1.7%) developed trace posterior subcapsular cataract, whereas no optic disk cupping or inflammation were noted. Sub-Tenon triamcinolone injection is commonly used to prevent inflammation at the time of retinal photocoagulation treatment in pediatric patients. It has a favorable safety profile in relation to intraocular pressure elevation and cataract formation. There was no requirement for intraocular pressure-lowering medications or surgical interventions.

Innate immune response after BNT162b2 COVID-19 vaccination associates with reactogenicity

BackgroundThe innate immune response is important for the development of the specific adaptive immunity, however it may also be associated with reactogenicity after vaccination. We explore the association between innate responsiveness, reactogenicity, and antibody response after first COVID-19 vaccination. MethodsWe included 146 healthy Dutch individuals aged 12–59 who received their first BNT162b2 (Comirnaty, Pfizer) COVID-19 vaccination. Data on reactogenicity were collected for each individual through daily questionnaires from day 0–5 after vaccination. From 60 participants, serum (adults) and plasma (adolescents) samples were collected before and/or 2 ± 1 days after vaccination to measure cytokines/chemokines as markers for innate responsiveness. Each individual was categorised into innate low, intermediate and high responder based on above or below the median value for each analyte detected after vaccination. For 137 participants, serum was collected at day 28 after vaccination for Spike S1- and RBD-antibody concentration. The associations between reactogenicity and/or innate responsiveness and/or log-transformed antibody concentration were explored using logistic and linear regressions. ResultsMost participants (85 %) reported both local and systemic symptoms after vaccination. Two participants reported no symptoms. More than half (54 %) reported one or more moderate symptoms. Significantly higher levels of pro-inflammatory mediators CXCL9, CXCL10, CXCL11, IFNγ and CCL20 in adults, and CXCL9, CXCL10 and CXCL11 in adolescents, were found after vaccination. Participants who showed high innate immune responsiveness had higher odds (OR 6.0; 95 % CI 1.4–33) of experiencing one or more moderate symptoms. No association was found between innate responsiveness or having one or more moderate symptoms with Spike S1- or RBD-antibody concentration at day 28 after vaccination. ConclusionOur results suggest an association between the strength of the innate immune response and the severity of reactogenicity to SARS-CoV-2 vaccination. However, more research is needed to understand the relation between reactogenicity and immunogenicity of COVID-19 vaccines.

The Association between the Social Vulnerability Index and Access to California High School Athletic Trainers.

Social determinants of health are known to affect overall access to youth sports, however, it is not fully understood how multiple social determinants of health may impact access to school-based athletic training services. To determine the relationship between Social Vulnerability Index (SVI) scores on access to high school-based athletic trainers in California. Retrospective, cross-sectional study. Online survey. California Interscholastic Federation (CIF) high school respondents of the 2022-23 Participation Census. Association between Social Vulnerability Index scores and access to school-based athletic trainer services. This study uses data from CIF high school respondents of the 2022-23 Participation Census. School addresses were used to extract SVI scores from the U.S. Census Bureau. Separate multivariable logistic regressions and generalized linear mixed effects models assessed the relationships between access to school-based athletic training services and SVI scores at the census and county levels. There were 1,598 respondent schools (65% public, 24% private, and 11% charter). 49% of schools reported having an athletic trainer, of which 41% were certified. Adjusted analyses revealed that increased vulnerability in household characteristics was associated with lower odds of access to athletic trainers and certified athletic trainers at both county (OR: 0.89 (95% CI: 0.80, 0.99); p = .04) and census tract levels (OR: 0.93 (95% CI: 0.89, 0.97); p = .002). Increased vulnerability in socioeconomic status was associated with lower odds of having an certified athletic trainer at the census tract level (OR: 0.94 (95% CI: 0.89, 0.98); p = .006), but not the county level (p = .16). Increased vulnerability in household characteristics is associated with decreased odds of access to high school-based athletic training services.

Pharmacogenetic and microRNA mechanisms of beta blocker use on bone.

Motivated by studies showing an association between beta blocker (BB) use and positive bone outcomes, a pilot randomized control trial (RCT) was performed at the Mayo Clinic which randomized postmenopausal women to placebo, propranolol (40 or 80 mg twice daily), atenolol (50 mg/day), or nebivolol (5 mg/day) to determine changes in bone turnover markers (BTMs) and in bone mineral density (BMD) over 20 weeks. Pharmacogenetic effects and microRNA-mediated mechanisms involving beta adrenergic receptor and related genes have previously been found. We sought to validate these effects and discover new candidates in an ancillary study to the pilot clinical trial. We genotyped all participants and performed microRNA (miRNA) sequencing at baseline and at 20 weeks for 24 participants from the atenolol or placebo groups. We discovered several variants in ADRB1, ADRB2, and HDAC4 which showed significant pharmacogenetic effects with BMD at multiple sites and with BTMs. Our miRNA results showed a significant treatment effect for miR-19a-3p over time with atenolol use in the low-responder group compared to placebo. Overall, the longitudinal miRNA analysis showed a large number of miRNAs which were up-regulated over the trial in the low responders but not the high responders compared to placebo, of which miR-19a-3p was one example. Finally, we compared the response to atenolol treatment for cardiovascular traits (pulse, blood pressure) with the response for the bone resorption marker, CTX, and found a largely independent effect. Our results have implications for personalized therapy and for understanding mechanisms of BB treatment effect on bone.

A study of universal values of sports in high schools based on ethnicity

Problems: Sports in high school are not just physical exercise; they also teach values that will shape students' behavior and personalities in the future. Sports shape one's character and ethics significantly through teaching universal values such as discipline, sportsmanship, honesty, and teamwork. Due to its diverse ethnic population, Indonesia faces its own difficulties in incorporating the universal values of sports into its education system. Purpose: Therefore, it is important to conduct research on the universal values of sports at the high school level from an ethnic perspective to understand the socio-cultural dynamics that occur in Indonesia. Methods: The research instrument used was a questionnaire. The study involved 261 high school student respondents, consisting of 97 Lampung ethnicities and 164 non-Lampung ethnicities, aged between 14 and 18 years. The instrument was to measure the universal values of sport, which consisted of six assessed components. Results: Analysis of the Mann-Whitney u test showed that the sig (2-tailed) value of 0.325 was greater than 0.05, indicating that there was no significant difference in the distribution of universal sports values between the two ethnic groups Lampung and Non-Lampung. Conclusion: Following up on the findings of this study, diverse cultural perspectives are essential for educational programs and approaches objectives, methods, and research results.

Effects of One-Year Anti-seizure Treatment with Add-On Cenobamate on Bone Density and Bone Turnover in Adults with Drug-Resistant Focal Epilepsy: An Observational Study.

Cenobamate is a novel anti-seizure medication (ASM) with unusually high responder rates even in patients with refractory epilepsy. Due to its enzyme-inducing properties, cenobamate could negatively affect bone metabolism, similar to other ASMs; however, effects of long-term cenobamate treatment on bone health have not yet been investigated. The aim of this longitudinal observational study was to assess the effects of 1 year of continuous, adjunctive cenobamate treatment on bone health in patients with drug-resistant, focal epilepsy. Adult patients from a tertiary epilepsy centre received cenobamate add-on to their concomitant anti-seizure medication. Bone mineral density at femoral neck and lumbar spine, as well as bone formation biomarkers, electrolytes and liver enzymes in serum were assessed at baseline and after 12 months of continuous cenobamate therapy. Forty-seven patients (29 male, median age 40 years) were included in the study. Median daily dose of cenobamate at 12 months was 250 mg. Moderate, yet statistically significant reduction of the T-score at femoral neck but not lumbar spine was found after 1 year of cenobamate treatment, also in a subgroup of patients (n = 37) without enzyme inducers in the comedication. Additionally, we observed statistically significant changes in bone formation biomarkers: decreased serum level of osteocalcin and increased bone-specific alkaline phosphatase. Bone minerals (calcium and phosphorus) as well as vitamin D3 remained unchanged. Parathormone was statistically significantly reduced. There was a highly statistically significant increase in serum gamma-glutamyl transferase (GGT) levels after 12 months of treatment, reflecting an underlying hepatic enzyme induction by cenobamate. A statistically significant decrease of the T-score at femoral neck, as well as prominent alterations in the bone formation biomarkers, suggest an increase in bone turnover after 1 year of cenobamate treatment. The underlying mechanism is most likely attributed to the hepatic enzyme activation, indicated by a prominent elevation of serum GGT. The results alert for bone density control in susceptible patient groups. DRKS00027568, March 2, 2022 retrospectively registered.

Children's Individual Differences in the Responses to a New Method for Physical Education.

Children's fundamental movement skills (FMS) require planned and guided interventions to develop appropriately. We investigated the effect of a novel Physical Education (PE) method to develop children's object control, locomotor skills, and motor competence. Further, we examined children's trainability, i.e., their differential responses to the new method, and identified low and high responders to the intervention. The study lasted three months and included six to seven-year-old children in two groups: control (the current, official PE program; n = 38) and experimental (the new method; n = 52). Twelve FMS [object control (OC), locomotor (LO)] were reliably assessed using the Meu Educativo® app. Using a mixed-effects model, results showed that the experimental group experienced greater changes (p < 0.05) than the control group in OC and LO. Positive individual changes were more frequent with the new method, but children showed a similar pattern in their interindividual variability in both methods. There was a greater reduction in the number of children with lower proficiency in the experimental group. In sum, the new PE method proved superior to the current, official one. Individual responses to the new method showed considerable variation, highlighting the need for personalization in teaching strategies and necessary support for children with lower proficiency levels, ensuring that no child is left behind in their motor development process.

Mass cytometry reveals cellular correlates of immune response heterogeneity to SARS-CoV-2 vaccination in the elderly

Heterogeneity in vaccine response, particularly in vulnerable populations like the elderly, represents a significant public health challenge. We conducted an in-depth examination of immune cell profiles before and after SARS-CoV-2 vaccination utilizing mass cytometry in a cohort of healthy Norwegian seniors (65–80 years). We have demonstrated that higher pre-vaccination frequencies of CD27+IgD- class-switched memory B cells and subsets of CD27-CD24+CD38+ transitional B cells were associated with a robust vaccine response. Post-vaccination, high responders exhibited increased frequencies of IFN-γ+CD4+ T cells with antigen recall and a concurrent decrease in CCR6(+) TH cell subset frequencies compared to low responders. The presence of a γδ T cell subset displaying polyfunctional cytokine responses was also associated with better vaccine response in the elderly. This in-depth profiling sheds light on inherent differences in immune cell frequencies and functions that may offer insights for targeted vaccination strategies in older populations.

Impact of a Text Messaging Intervention as an In-Between Support to Diabetes Group Visits in Federally Qualified Health Centers: Cluster Randomized Controlled Study.

In the United States, 1 in 11 people receive primary care from a federally qualified health center (FQHC). Text messaging interventions (TMIs) are accessible ways to deliver health information, engage patients, and improve health outcomes in the health center setting. We aimed to evaluate the impact of a TMI implemented with a group visit (GV) intervention among patients with type 2 diabetes mellitus (T2DM) at FQHCs on patient-reported outcomes and clinical outcomes based on patient TMI engagement. A TMI was implemented for 11 health centers participating in a cluster randomized study of diabetes GVs in Midwestern FQHCs targeting adults with T2DM. FQHC patients participated in 6 monthly GVs either in person or online and a concurrent 25-week TMI. Outcome measures included clinical markers such as glycated hemoglobin A1c and patient-reported diabetes distress, diabetes self-care, diabetes self-efficacy, diabetes care knowledge, diabetes quality of life, diabetes social support, and TMI use and satisfaction. TMI response rate was calculated as responses to an SMS text message requesting a response divided by total messages requesting a response sent. Patients were grouped as high responders if their response rate was greater than or equal to the median response rate and low responders if their response rate was below the median. We conducted linear mixed models to compare high and low responders and within a group, adjusting for age, gender, GV attendance, and depression/anxiety at baseline. In total, 101 of 124 GV patients (81.5%) enrolled in the TMI. The average age of the population in the TMI was 53 years. Of the 101 respondents, 61 (60%) were racial or ethnic minorities, while 42 of 82 respondents (51%) had a high school diploma/General Education Development or less, and 56 of 80 respondents (71%) reported an annual income less than US $30,000. In addition, 70 of 81 respondents (86%) owned a smartphone and 74 of 80 respondents (93%) had an unlimited texting plan. The median response rate was 41% and the mean response rate was 41.6%. Adjusted models showed significantly improved diabetes knowledge (P<.001), foot care (P<.001), and exercise (P=.002) in high responders (n=34) compared to low responders (n=23) at 6 months. No group difference was found in glycated hemoglobin A1c. Within high responders, diabetes distress (P=.001), social support (P<.001), quality of life (P<.001), diabetes knowledge (P<.001), foot care (P<.001), and diet (P=.003) improved from baseline to 6 months. Low responders only improved in diabetes quality of life (P=.003) from baseline to 6 months. In a FQHC safety net population participating in a combined TMI and GV intervention, our study showed improved diabetes distress, social support, knowledge, self-care, self-efficacy, and quality of life among patients highly engaged in the SMS text messaging program.

Two-Year Outcomes Using Fast-Acting, Sub-Perception Therapy for Spinal Cord Stimulation: A European, Real-World, Multicenter Experience.

Background/Objectives: Over the last 20 years, spinal cord stimulation (SCS) has seen the development of various paresthesia-free paradigms. Recently, a novel modality has emerged (Fast-Acting Sub-perception Therapy, FAST) that engages the surrounding inhibition mechanism of action. We evaluated long-term, real-world outcomes of preferential FAST-SCS use in patients with chronic pain. Methods: In this multi-center, observational, consecutive case series, medical chart data from chronic pain patients preferentially using FAST-SCS (no exclusions) were retrospectively reviewed. Results: Data from 167 patients in 13 European centers were analyzed; 74% of patients suffered from persistent spine pain syndrome type 2 and 87% presented with low back and/or leg pain. At the last follow-up (mean 1.6 years), the numerical rating scale (NRS) overall pain score decreased by 5.1 ± 2.5 points versus baseline, from 8.0 ± 1.2 to 2.9 ± 2.2 (n = 167, p < 0.0001). 87% of patients reported ≥50% pain relief, and 55% were "high responders" with overall NRS pain scores ≤2/10. At the last follow-up, functional disability improved significantly (the Oswestry Disability Index reduced by 29.2 ± 21.5 points, n = 65, p < 0.0001) and patients had a significant gain in quality of life (EQ-5D-5L visual analog scale increased by 52.0 ± 26.9 points, n = 86, p < 0.0001). Results at the 2-year follow-up showed a sustained, substantial reduction in pain; 67% of patients were high responders and the NRS overall pain score decreased by 5.6 ± 2.4 versus baseline (n = 52, p < 0.0001). Conclusions: Our real-world outcomes suggest that in patients with chronic low back and/or leg pain, FAST-SCS therapy provided durable and profound pain relief and led to significant improvements in disability and quality of life.

Gingivitis Control in Children, Adolescents and Young Adults With Chronic Kidney Disease by a Need‐Related Programme: A Randomised Clinical Trial

ABSTRACTObjectivesChildren and young patients with chronic kidney disease (CKD) are at persistent risk of gingivitis despite usual preventive measures. This clinical study aimed to determine the efficacy of an intensive oral preventive programme (OPP) for young patients with CKD in treating plaque‐induced gingivitis modified by systemic factors.MethodsYoung patients with CKD (N = 30) were recruited/randomised to a need‐related OPP (n = 15) or treatment as usual (TAU) including mainly motivation and instructions (controls, n = 15) followed by a single intensive prophylactic appointment after 3 months. For the OPP group, depending on the baseline degree of inflammation (PBI) professional mechanical plaque removal, local chlorhexidine gel application and mouth rinse were applied at need‐related appointments focussing on local plaque control and reduction in inflammation.ResultsAfter 3 months OPP, lower plaque indices were found (2.62–0.66, p &lt; 0.05) in contrast to TAU (2.32–2.05, p &gt; 0.05) with differences between study groups (p &lt; 0.05). Regarding gingivitis, lower PBI values than baseline were observed in OPP (1.03–0.05, p &lt; 0.05) than TAU (1.15–1.00; p &gt; 0.05); OPP reductions (effect size) were higher than after a single intensive appointment (1.00–0.36; p &lt; 0.05). Degree of immunosuppressive therapy did not differ between groups throughout the study.ConclusionsYoung patients with CKD suffer from generalised gingivitis with increased bleeding sites. This moderate degree of inflammation shows a normal distribution of high and low plaque responders, with no pattern of impact for the degree of immunosuppression. Effectiveness and duration of preventive measures follow a dose–response principle. Therefore, need‐related preventive measures should be implemented and maintained in future regular care for CKD patients.Trial RegistrationGerman Clinical Trials Register, registration number: DRKS00010580

Identification of Functional Immune Biomarkers in Breast Cancer Patients.

Cancer immunotherapy has emerged as an effective, personalized treatment for certain patients, particularly for those with hematological malignancies. However, its efficacy in breast cancer has been marginal-perhaps due to cold, immune-excluded, or immune-desert tumors. Natural killer T (NKT) cells play a critical role in cancer immune surveillance and are reduced in cancer patients. Thus, we hypothesized that NKT cells could serve as a surrogate marker for immune function. In order to assess which breast cancer patients would likely benefit from immune cell-based therapies, we have developed a quantitative method to rapidly assess NKT function using stimulation with artificial antigen presenting cells followed by quantitative real-time PCR for IFN-γ. We observed a significant reduction in the percentage of circulating NKT cells in breast cancer patients, compared to healthy donors; however, the majority of patients had functional NKT cells. When we compared BC patients with highly functional NKT cells, as indicated by high IFN-γ induction, to those with little to no induction, following stimulation of NKT cells, there was no significant difference in NKT cell number between the groups, suggesting functional loss has more impact than physical loss of this subpopulation of T cells. In addition, we assessed the percentage of tumor-infiltrating lymphocytes and PD-L1 expression within the tumor microenvironment in the low and high responders. Further characterization of immune gene signatures in these groups identified a concomitant decrease in the induction of TNFα, LAG3, and LIGHT in the low responders. We next investigated the mechanisms by which breast cancers suppress NKT-mediated anti-tumor immune responses. We found that breast cancers secrete immunosuppressive lipids, and treatment with commonly prescribed medications that modulate lipid metabolism, can reduce tumor growth and restore NKT cell responses.

Examining the Empathy Profiles and Work Outcomes of Trauma Workers

Trauma work involves intervening with others enduring acute pain and suffering, often with heavy psychological and physical health impacts. An important question is whether dispositional empathy helps or hurts trauma workers in their occupational functioning. The current study addresses this gap in the research literature by using a person-centered approach to examine the empathy profiles and professional outcomes of a broad sample of trauma workers ( n = 315). We measured their trait empathy and organizational outcomes (occupational burnout, person-job fit, turnover intentions, job performance), and found three distinct empathy profiles which differed significantly in their occupational functioning. A ‘self-focused’ empathy profile (dominated by high personal distress responding) reported the worst functioning; an ‘other-oriented’ profile (high on perspective taking and empathic concern) had more positive functioning, and an unexpected ‘low reactivity’ profile (a full SD below the general population on empathy facets) showed the lowest exhaustion. Exploratory analyses revealed that first responders (e.g., police, firefighters, EMTs, paramedics) were overrepresented in the ‘low reactivity’ profile, while psychology-related professions (e.g., psychologists, counsellors, social workers) were underrepresented in that profile. The significance of these results, as well as their implications for empathy research and vocational counselling in the field of trauma work, are discussed.